Integrins as Unique Receptors for Vascular ControlMartinez-Lemus L.A.a · Wu X.a · Wilson E.a · Hill M.A.c · Davis G.E.b · Davis M.J.a · Meininger G.A.a
aDepartment of Medical Physiology, Division of Vascular Biology, Cardiovascular Research Institute, and bDepartment of Pathology and Laboratory Medicine, Texas A&M University System Health Science Center, College Station, Tex., USA, and cMicrovascular Biology Group, School of Medical Sciences, RMIT University, Bundoora, Australia
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Article / Publication Details
Cells within the vascular wall connect their cytoskeleton to the extracellular matrix (ECM) through a family of cell surface receptors known as integrins. The ability of integrins to act as a link between the extracellular and intracellular environments allows transmission of inside-out and outside-in signals capable of modulating diverse vascular phenomena. In this review we summarize what is currently known about the involvement of integrins in the control of vascular tone, permeability and remodeling. We discuss the capacity of integrins to act as detectors of injury-generated molecules derived from ECM proteins, as well as the putative role of integrins as mechanosensors for shear and tension. Particular attention is given to the mechanisms responsible for linking integrins to the control of vascular tone, and we review the intracellular signaling pathways involved in effecting the vascular responses elicited by integrin activation. Finally, the involvement of integrins in vascular remodeling and vascular disease is analyzed. Considerable evidence strongly indicates that integrins are involved in both acute and chronic vascular control. Understanding the elements and the sequence of events linking integrins with vasoregulation is important for deciphering phenomena such as the pressure-dependent myogenic response, flow-dependent changes in vascular diameter, and vascular remodeling as they occur in physiological and pathological conditions. Further understanding of the role of integrins in vascular control holds promise as new avenues for prophylactic and therapeutic manipulation of vascular phenomena.
© 2003 S. Karger AG, Basel
- Humphries MJ: Integrin structure. Biochem Soc Trans 2000;28:311–339.
- Leitinger B, McDowall A, Stanley P, Hogg N: The regulation of integrin function by Ca(2+). Biochim Biophys Acta 2000;1498:91–98.
- Plow EF, Haas TA, Zhang L, Loftus J, Smith JW: Ligand binding to integrins. J Biol Chem 2000;275:21785–21788.
- Schwartz MA: Integrin signaling revisited. Trends Cell Biol 2001;11:466–470.
- Vuori K: Integrin signaling: Tyrosine phosphorylation events in focal adhesions. J Membr Biol 1998;165:191–199.
- Xiong JP, Stehle T, Diefenbach B, Zhang R, Dunker R, Scott DL, Joachimiak A, Goodman SL, Arnaout MA: Crystal structure of the extracellular segment of integrin αVβ3. Science 2001;294:339–345.
- Giancotti FG, Ruoslahti E: Integrin signaling. Science 1999;285:1028–1032.
- Maniotis AJ, Chen CS, Ingber DE: Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci USA 1997;94:849–854.
- Pommerenke H, Schreiber E, Durr F, Nebe B, Hahnel C, Moller W, Rychly J: Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. Eur J Cell Biol 1996;70:157–164.
- Davis GE, Bayless KJ, Davis MJ, Meininger GA: Regulation of tissue injury responses by the exposure of matricryptic sites within extracellular matrix molecules. Am J Pathol 2000;156:1489–1498.
- Davis GE: Affinity of integrins for damaged extracellular matrix: αvβ3 binds to denatured collagen type I through RGD sites. Biochem Biophys Res Commun 1992;182:1025–1031.
- Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG, Quaranta V: Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 1997;277:225–228.
Sage H: Pieces of eight: Bioactive fragments of extracellular proteins as regulators of angiogenesis. Trends Cell Biol 1997;7:182–186.
- Muller JM, Chilian WM, Davis MJ: Integrin signaling transduces shear stress-dependent vasodilation of coronary arterioles. Circ Res 1997;80:320–326.
Madden JA, Christman NJ: Integrin signaling, free radicals, and tyrosine kinase mediate flow constriction in isolated cerebral arteries. Am J Physiol 1999;277:H2264–H2271.
Davis MJ, Wu X, Nurkiewicz TR, Kawasaki J, Davis GE, Hill MA, Meininger GA: Integrins and mechanotransduction of the vascular myogenic response. Am J Physiol 2001;280:H1427–H1433.
- Mogford JE, Davis GE, Platts SH, Meininger GA: Vascular smooth muscle alpha v beta 3 integrin mediates arteriolar vasodilation in response to RGD peptides. Circ Res 1996;79:821–826.
- Mogford JE, Davis GE, Meininger GA: RGDN peptide interaction with endothelial α5β1 integrin causes sustained endothelin-dependent vasoconstriction of rat skeletal muscle arterioles. J Clin Invest 1997;100:1647–1653.
- Lipke DW, Soltis EE, Fiscus RR, Yang L, Newman PS, Aziz SM: RGD-containing peptides induce endothelium-dependent and independent vasorelaxations of rat aortic rings. Regul Pept 1996;63:23–29.
Yip KP, Marsh DJ: An Arg-Gly-Asp peptide stimulates constriction in rat afferent arteriole. Am J Physiol 1997;273:F768–F776.
- Laplante C, St-Pierre S, Beaulieu AD, Marceau F: Small fibronectin fragments induce endothelium-dependent vascular relaxations. Can J Physiol Pharmacol 1988;66:745–748.
- Rupp PA, Little CD: Integrins in vascular development. Circ Res 2001;89:566–572.
Stupack DG, Cheresh DA: ECM remodeling regulates angiogenesis: Endothelial integrins look for new ligands. Sci STKE 2002;2002:PE7.
Glukhova MA, Koteliansky VE: Integrins, cytoskeletal and extracellular matrix proteins in developing smooth muscle cells of human aorta; in Schwartz SM, Mecham RP (eds): The Vascular Smooth Muscle Cell: Molecular and Biological Responses to the Extracellular Matrix. San Diego, Academic Press, 1995, pp 37–79.
Moiseeva EP: Adhesion receptors of vascular smooth muscle cells and their functions. Cardiovasc Res 2001;52:372–386.
- Meininger GA, Fehr KL, Yates MB: Anatomic and hemodynamic characteristics of the blood vessels feeding the cremaster skeletal muscle in the rat. Microvasc Res 1987;33:81–97.
- Meininger GA, Fehr KL, Yates MB, Borders JL, Granger HJ: Hemodynamic characteristics of the intestinal microcirculation in renal hypertension. Hypertension 1986;8:66–75.
- Waitkus-Edwards KR, Martinez-Lemus LA, Wu X, Trzeciakowski JP, Davis MJ, Davis GE, Meininger GA: Alpha(4)beta(1) Integrin activation of L-type calcium channels in vascular smooth muscle causes arteriole vasoconstriction. Circ Res 2002;90:473–480.
- Wu X, Davis GE, Meininger GA, Wilson E, Davis MJ: Regulation of the L-type calcium channel by alpha 5 beta 1 integrin requires signaling between focal adhesion proteins. J Biol Chem 2001;276:30285–30292.
Ge M, Ryan TJ, Lum H, Malik AB: Fibrinogen degradation product fragment D increases endothelial monolayer permeability. Am J Physiol 1991;261:L283–L289.
- Hocking DC, Smith RK, McKeown-Longo PJ: A novel role for the integrin-binding III-10 module in fibronectin matrix assembly. J Cell Biol 1996;133:431–444.
- Rowland FN, Donovan MJ, Picciano PT, Wilner GD, Kreutzer DL: Fibrin-mediated vascular injury. Identification of fibrin peptides that mediate endothelial cell retraction. Am J Pathol 1984;117:418–428.
Sottile J, Hocking DC, Swiatek PJ: Fibronectin matrix assembly enhances adhesion-dependent cell growth. J Cell Sci 1998;111(Pt 19):2933–2943.
- Wu MH, Ustinova E, Granger HJ: Integrin binding to fibronectin and vitronectin maintains the barrier function of isolated porcine coronary venules. J Physiol 2001;532:785–791.
- Xu J, Rodriguez D, Petitclerc E, Kim JJ, Hangai M, Moon YS, Davis GE, Brooks PC, Yuen SM: Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. J Cell Biol 2001;154:1069–1079.
- Yokasaki Y, Sheppard D: Mapping of the cryptic integrin-binding site in osteopontin suggests a new mechanism by which thrombin can regulate inflammation and tissue repair. Trends Cardiovasc Med 2000;10:155–159.
- Dvorak HF, Nagy JA, Berse B, Brown LF, Yeo KT, Yeo TK, Dvorak AM, van de Water L, Sioussat TM, Senger DR: Vascular permeability factor, fibrin, and the pathogenesis of tumor stroma formation. Ann NY Acad Sci 1992;667:101–111.
- Ravanti L, Kahari VM: Matrix metalloproteinases in wound repair (review). Int J Mol Med 2000;6:391–407.
- Schwarzbauer JE, Sechler JL: Fibronectin fibrillogenesis: A paradigm for extracellular matrix assembly. Curr Opin Cell Biol 1999;11:622–627.
- Ugarova TP, Zamarron C, Veklich Y, Bowditch RD, Ginsberg MH, Weisel JW, Plow EF: Conformational transitions in the cell binding domain of fibronectin. Biochemistry 1995;34:4457–4466.
- Zamarron C, Ginsberg MH, Plow EF: Monoclonal antibodies specific for a conformationally altered state of fibrinogen. Thromb Haemost 1990;64:41–46.
- Krammer A, Lu H, Isralewitz B, Schulten K, Vogel V: Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch. Proc Natl Acad Sci USA 1999;96:1351–1356.
- Altroff H, van der Walle CF, Asselin J, Fairless R, Campbell ID, Mardon HJ: The eighth FIII domain of human fibronectin promotes integrin α5β1 binding via stabilization of the ninth FIII domain. J Biol Chem 2001;276:38885–38892.
- Garcia AJ, Schwarzbauer JE, Boettiger D: Distinct activation states of α5β1 integrin show differential binding to RGD and synergy domains of fibronectin. Biochemistry 2002;41:9063–9069.
- Garcia AJ, Vega MD, Boettiger D: Modulation of cell proliferation and differentiation through substrate-dependent changes in fibronectin conformation. Mol Biol Cell 1999;10:785–798.
Krammer A, Craig D, Thomas WE, Schulten K, Vogel V: A structural model for force regulated integrin binding to fibronectin’s RGD-synergy site. Matrix Biol 2002;21:139–147.
- Ohashi T, Kiehart DP, Erickson HP: Dynamics and elasticity of the fibronectin matrix in living cell culture visualized by fibronectin-green fluorescent protein. Proc Natl Acad Sci USA 1999;96:2153–2158.
- Erickson HP: Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin. Proc Natl Acad Sci USA 1994;91:10114–10118.
- Hocking DC, Sottile J, McKeown-Longo PJ: Fibronectin’s III-1 module contains a conformation-dependent binding site for the amino-terminal region of fibronectin. J Biol Chem 1994;269:19183–19187.
- Ingham KC, Brew SA, Huff S, Litvinovich SV: Cryptic self-association sites in type III modules of fibronectin. J Biol Chem 1997;272:1718–1724.
- Langenbach KJ, Sottile J: Identification of protein-disulfide isomerase activity in fibronectin. J Biol Chem 1999;274:7032–7038.
- Morla A, Zhang Z, Ruoslahti E: Superfibronectin is a functionally distinct form of fibronectin. Nature 1994;367:193–196.
- Zhong C, Chrzanowska-Wodnicka M, Brown J, Shaub A, Belkin AM, Burridge K: Rho-mediated contractility exposes a cryptic site in fibronectin and induces fibronectin matrix assembly. J Cell Biol 1998;141:539–551.
- Kappert K, Blaschke F, Meehan WP, Kawano H, Grill M, Fleck E, Hsueh WA, Law RE, Graf K: Integrins αVβ3 and αVβ5 mediate VSMC migration and are elevated during neointima formation in the rat aorta. Basic Res Cardiol 2001;96:42–49.
- Srivatsa SS, Fitzpatrick LA, Tsao PW, Reilly TM, Holmes DR Jr, Schwartz RS, Mousa SA: Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: Evidence for the functional importance of integrin alpha v beta 3 and osteopontin expression during neointima formation. Cardiovasc Res 1997;36:408–428.
- Bayless KJ, Davis GE: Identification of dual α4β1 integrin binding sites within a 38 amino acid domain in the N-terminal thrombin fragment of human osteopontin. J Biol Chem 2001;276:13483–13489.
- Yokosaki Y, Matsuura N, Sasaki T, Murakami I, Schneider H, Higashiyama S, Saitoh Y, Yamakido M, Taooka Y, Sheppard D: The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. J Biol Chem 1999;274:36328–36334.
- Moses S, Franzen A, Lovdahl C, Hultgardh-Nilsson A: Injury-induced osteopontin gene expression in rat arterial smooth muscle cells is dependent on mitogen-activated protein kinases ERK1/ERK2. Arch Biochem Biophys 2001;396:133–137.
- Bayless KJ, Davis GE, Meininger GA: Isolation and biological properties of osteopontin from bovine milk. Protein Expr Purif 1997;9:309–314.
- Ergun S, Kilic N, Wurmbach JH, Ebrahimnejad A, Fernando M, Sevinc S, Kilic E, Chalajour F, Fiedler W, Lauke H, Lamszus K, Hammerer P, Weil J, Herbst H, Folkman J: Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes. Angiogenesis 2001;4:193–206.
Sasaki T, Hohenester E, Timpl R: Structure and function of collagen-derived endostatin inhibitors of angiogenesis. IUBMB Life 2002;53:77–84.
- Shi W, Teschendorf C, Muzyczka N, Siemann DW: Adeno-associated virus-mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo. Cancer Gene Ther 2002;9:513–521.
- Petitclerc E, Boutaud A, Prestayko A, Xu J, Sado Y, Ninomiya Y, Sarras MP Jr, Hudson BG, Brooks PC: New functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo. J Biol Chem 2000;275:8051–8061.
- Maeshima Y, Yerramalla UL, Dhanabal M, Holthaus KA, Barbashov S, Kharbanda S, Reimer C, Manfredi M, Dickerson WM, Kalluri R: Extracellular matrix-derived peptide binds to alpha(v)beta(3) integrin and inhibits angiogenesis. J Biol Chem 2001;276:31959–1968.
- Boutaud A, Borza DB, Bondar O, Gunwar S, Netzer KO, Singh N, Ninomiya Y, Sado Y, Noelken ME, Hudson BG: Type IV collagen of the glomerular basement membrane. Evidence that the chain specificity of network assembly is encoded by the noncollagenous NC1 domains. J Biol Chem 2000;275:30716–30724.
- Sundaramoorthy M, Meiyappan M, Todd P, Hudson BG: Crystal structure of NC1 domains: Structural basis for type IV collagen assembly in basement membranes. J Biol Chem 2002;277:31142–31153.
- Davis GE, Pintar Allen KA, Salazar R, Maxwell SA: Matrix metalloproteinase-1 and -9 activation by plasmin regulates a novel endothelial cell-mediated mechanism of collagen gel contraction and capillary tube regression in three-dimensional collagen matrices. J Cell Sci 2001;114:917–930.
- O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J: Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell 1997;88:277–285.
- O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J: Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994;79:315–328.
- O’Reilly MS, Wiederschain D, Stetler-Stevenson WG, Folkman J, Moses MA: Regulation of angiostatin production by matrix metalloproteinase-2 in a model of concomitant resistance. J Biol Chem 1999;274:29568–29571.
- Bacharach E, Itin A, Keshet E: Apposition-dependent induction of plasminogen activator inhibitor type 1 expression: A mechanism for balancing pericellular proteolysis during angiogenesis. Blood 1998;92:939–945.
- Bajou K, Noel A, Gerard RD, Masson V, Brunner N, Holst-Hansen C, Skobe M, Fusenig NE, Carmeliet P, Collen D, Foidart JM: Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 1998;4:923–928.
- Pinsky DJ, Liao H, Lawson CA, Yan SF, Chen J, Carmeliet P, Loskutoff DJ, Stern DM: Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J Clin Invest 1998;102:919–928.
- Bajou K, Masson V, Gerard RD, Schmitt PM, Albert V, Praus M, Lund LR, Frandsen TL, Brunner N, Dano K, Fusenig NE, Weidle U, Carmeliet G, Loskutoff D, Collen D, Carmeliet P, Foidart JM, Noel A: The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies. J Cell Biol 2001;152:777–784.
- Deng G, Curriden SA, Wang S, Rosenberg S, Loskutoff DJ: Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? J Cell Biol 1996;134:1563–1571.
- Devy L, Blacher S, Grignet-Debrus C, Bajou K, Masson V, Gerard RD, Gils A, Carmeliet G, Carmeliet P, Declerck PJ, Noel A, Foidart JM: The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J 2002;16:147–154.
- Nagy Z, Kolev K, Csonka E, Vastag M, Machovich R: Perturbation of the integrity of the blood-brain barrier by fibrinolytic enzymes. Blood Coagul Fibrinolysis 1998;9:471–478.
- Sueishi K, Nanno S, Tanaka K: Permeability enhancing and chemotactic activities of lower molecular weight degradation products of human fibrinogen. Thromb Haemost 1981;45:90–94.
Ortega N, L’Faqihi FE, Plouet J: Control of vascular endothelial growth factor angiogenic activity by the extracellular matrix. Biol Cell 1998;90:381–390.
- Vlodavsky I, Bar-Shavit R, Ishai-Michaeli R, Bashkin P, Fuks Z: Extracellular sequestration and release of fibroblast growth factor: A regulatory mechanism? Trends Biochem Sci 1991;16:268–271.
- Pierschbacher MD, Ruoslahti E: Influence of stereochemistry of the sequence Arg-Gly-Asp-Xaa on binding specificity in cell adhesion. J Biol Chem 1987;262:17294–17298.
Schnapp LM, Goswami S, Rienzi N, Koteliansky VE, Gotwals P, Schachter EN: Integrins inhibit angiotensin II-induced contraction in rat aortic rings. Regul Pept 1998;77:177–183.
Hein TW, Platts SH, Waitkus-Edwards KR, Kuo L, Mousa SA, Meininger GA: Integrin-binding peptides containing RGD produce coronary arteriolar dilation via cyclooxygenase activation. Am J Physiol 2001;281:H2378–H2384.
- D’Angelo G, Meininger GA: Transduction mechanisms involved in the regulation of myogenic activity. Hypertension 1994;23:1096–1105.
Davis MJ, Meininger GA: The myogenic mechanism response in microvascular networks; in Rubanyi GA (ed): Mechanotransduction by the vascular wall. Mount Kisco, Futura Publishing, 1993.
Meininger GA, Davis MJ: Cellular mechanisms involved in the vascular myogenic response. Am J Physiol 1992;263:H647–H659.
- Wu X, Mogford JE, Platts SH, Davis GE, Meininger GA, Davis MJ: Modulation of calcium current in arteriolar smooth muscle by αv β3 and α5 β1 integrin ligands. J Cell Biol 1998;143:241–252.
- Du XP, Plow EF, Frelinger AL 3rd, O’Toole TE, Loftus JC, Ginsberg MH: Ligands ‘activate’ integrin alpha IIb beta 3 (platelet GPIIb-IIIa). Cell 1991;65:409–416.
- Takagi J, Petre BM, Walz T, Springer TA: Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 2002;110:599–611.
- Bazzoni G, Ma L, Blue ML, Hemler ME: Divalent cations and ligands induce conformational changes that are highly divergent among β1 integrins. J Biol Chem 1998;273:6670–6678.
- Diaz-Gonzalez F, Forsyth J, Steiner B, Ginsberg MH: Trans-dominant inhibition of integrin function. Mol Biol Cell 1996;7:1939–1951.
Dogic D, Rousselle P, Aumailley M: Cell adhesion to laminin 1 or 5 induces isoform-specific clustering of integrins and other focal adhesion components. J Cell Sci 1998;111(pt 6):793–802.
- Lichtner RB, Howlett AR, Lerch M, Xuan JA, Brink J, Langton-Webster B, Schneider MR: Negative cooperativity between alpha 3 beta 1 and alpha 2 beta 1 integrins in human mammary carcinoma MDA MB 231 cells. Exp Cell Res 1998;240:368–376.
- Tomatis D, Echtermayer F, Schober S, Balzac F, Retta SF, Silengo L, Tarone G: The muscle-specific laminin receptor α7 β1 integrin negatively regulates α6 β1 fibronectin receptor function. Exp Cell Res 1999;246:421–432.
Meininger GA, Martinez-Lemus LA, Sun Z, Trache A, Wu X, Wilson E, Davis MJ, Pohl U: Role of extracellular matrix-integrin interactions in short and long-term responses to pressure. J Vasc Res 2002;39(suppl 1):90.
- Dieterich P, Odenthal-Schnittler M, Mrowietz C, Kramer M, Sasse L, Oberleithner H, Schnittler HJ: Quantitative morphodynamics of endothelial cells within confluent cultures in response to fluid shear stress. Biophys J 2000;79:1285–1297.
- Frame MD, Sarelius IH: Flow-induced cytoskeletal changes in endothelial cells growing on curved surfaces. Microcirculation 2000;7:419–427.
- Kataoka N, Ujita S, Sato M: Effect of flow direction on the morphological responses of cultured bovine aortic endothelial cells. Med Biol Eng Comput 1998;36:122–128.
- Sato M, Ohshima N: Flow-induced changes in shape and cytoskeletal structure of vascular endothelial cells. Biorheology 1994;31:143–153.
- Davies PF, Robotewskyj A, Griem ML: Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces. J Clin Invest 1994;93:2031–2038.
- Jalali S, del Pozo MA, Chen K, Miao H, Li Y, Schwartz MA, Shyy JY, Chien S: Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc Natl Acad Sci USA 2001;98:1042–1046.
- Chen KD, Li YS, Kim M, Li S, Yuan S, Chien S, Shyy JY: Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J Biol Chem 1999;274:18393–18400.
- Ishida T, Peterson TE, Kovach NL, Berk BC: MAP kinase activation by flow in endothelial cells. Role of beta 1 integrins and tyrosine kinases. Circ Res 1996;79:310–316.
Kuo L, Chilian WM, Davis MJ: Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels. Am J Physiol 1991;261:H1706–H1715.
- Gloe T, Sohn HY, Meininger GA, Pohl U: Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via integrin alpha(v)beta3. J Biol Chem 2002;277:23453–23458.
Hecker M, Mulsch A, Bassenge E, Busse R: Vasoconstriction and increased flow: Two principal mechanisms of shear stress-dependent endothelial autacoid release. Am J Physiol 1993;265:H828–H833.
Huang A, Sun D, Carroll MA, Jiang H, Smith CJ, Connetta JA, Falck JR, Shesely EG, Koller A, Kaley G: EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice. Am J Physiol 2001;280:H2462–H2469.
- Huang A, Wu Y, Sun D, Koller A, Kaley G: Effect of estrogen on flow-induced dilation in NO deficiency: Role of prostaglandins and EDHF. J Appl Physiol 2001;91:2561–2566.
- Koller A, Sun D, Kaley G: Role of shear stress and endothelial prostaglandins in flow- and viscosity-induced dilation of arterioles in vitro. Circ Res 1993;72:1276–1284.
Kuchan MJ, Frangos JA: Shear stress regulates endothelin-1 release via protein kinase C and cGMP in cultured endothelial cells. Am J Physiol 1993;264:H150–H156.
Pohl U, Herlan K, Huang A, Bassenge E: EDRF-mediated shear-induced dilation opposes myogenic vasoconstriction in small rabbit arteries. Am J Physiol 1991;261:H2016–H2023.
Rubio R, Ceballos G: Role of the endothelial glycocalyx in dromotropic, inotropic, and arrythmogenic effects of coronary flow. Am J Physiol 2000;278:H106–H116.
- Davies PF, Barbee KA, Volin MV, Robotewskyj A, Chen J, Joseph L, Griem ML, Wernick MN, Jacobs E, Polacek DC, dePaola N, Barakat AI: Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction. Annu Rev Physiol 1997;59:527–549.
Kuo L, Davis MJ, Chilian WM: Endothelium-dependent, flow-induced dilation of isolated coronary arterioles. Am J Physiol 1990;259:H1063–H1070.
- Gallis B, Corthals GL, Goodlett DR, Ueba H, Kim F, Presnell SR, Figeys D, Harrison DG, Berk BC, Aebersold R, Corson MA: Identification of flow-dependent endothelial nitric-oxide synthase phosphorylation sites by mass spectrometry and regulation of phosphorylation and nitric oxide production by the phosphatidylinositol 3-kinase inhibitor LY294002. J Biol Chem 1999;274:30101–30108.
Bryan RM Jr, Marrelli SP, Steenberg ML, Schildmeyer LA, Johnson TD: Effects of luminal shear stress on cerebral arteries and arterioles. Am J Physiol 2001;280:H2011–H2022.
- Olesen SP, Clapham DE, Davies PF: Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 1988;331:168–170.
- Hoger JH, Ilyin VI, Forsyth S, Hoger A: Shear stress regulates the endothelial Kir2.1 ion channel. Proc Natl Acad Sci USA 2002;99:7780–7785.
- Tzima E, del Pozo MA, Shattil SJ, Chien S, Schwartz MA: Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. Embo J 2001;20:4639–4647.
- Urbich C, Walter DH, Zeiher AM, Dimmeler S: Laminar shear stress upregulates integrin expression: Role in endothelial cell adhesion and apoptosis. Circ Res 2000;87:683–689.
- Urbich C, Dernbach E, Reissner A, Vasa M, Zeiher AM, Dimmeler S: Shear stress-induced endothelial cell migration involves integrin signaling via the fibronectin receptor subunits alpha(5) and beta(1). Arterioscler Thromb Vasc Biol 2002;22:69–75.
- Liu Y, Chen BP, Lu M, Zhu Y, Stemerman MB, Chien S, Shyy JY: Shear stress activation of SREBP1 in endothelial cells is mediated by integrins. Arterioscler Thromb Vasc Biol 2002;22:76–81.
Frame MD: Conducted signals within arteriolar networks initiated by bioactive amino acids. Am J Physiol 1999;276:H1012–H1021.
Frame MD: Increased flow precedes remote arteriolar dilations for some microapplied agonists. Am J Physiol 2000;278:H1186–H1195.
Rotundo RF, Curtis TM, Shah MD, Gao B, Mastrangelo A, LaFlamme SE, Saba TM: TNF-alpha disruption of lung endothelial integrity: Reduced integrin mediated adhesion to fibronectin. Am J Physiol 2002;282:L316–L329.
Curtis TM, McKeown-Longo PJ, Vincent PA, Homan SM, Wheatley EM, Saba TM: Fibronectin attenuates increased endothelial monolayer permeability after RGD peptide, anti-alpha 5 beta 1, or TNF-alpha exposure. Am J Physiol 1995;269:L248–L260.
Qiao RL, Yan W, Lum H, Malik AB: Arg-Gly-Asp peptide increases endothelial hydraulic conductivity: Comparison with thrombin response. Am J Physiol 1995;269:C110–C117.
- Reed RK, Berg A, Gjerde EA, Rubin K: Control of interstitial fluid pressure: Role of β1-integrins. Semin Nephrol 2001;21:222–230.
Muller JM, Davis MJ, Kuo L, Chilian WM: Changes in coronary endothelial cell Ca2+ concentration during shear stress- and agonist-induced vasodilation. Am J Physiol 1999;276:H1706–H1714.
- Shimoda LA, Norins NA, Madden JA: Flow-induced responses in cat isolated pulmonary arteries. J Appl Physiol 1997;83:1617–1622.
Wang X, van Breemen C: Depolarization-mediated inhibition of Ca(2+) entry in endothelial cells. Am J Physiol 1999;277:H1498–H1504.
- Becchetti A, Arcangeli A, Del Bene MR, Olivotto M, Wanke E: Response to fibronectin-integrin interaction in leukaemia cells: Delayed enhancing of a K+ current. Proc R Soc Lond B Biol Sci 1992;248:235–240.
- Levite M, Cahalon L, Peretz A, Hershkoviz R, Sobko A, Ariel A, Desai R, Attali B, Lider O: Extracellular K(+) and opening of voltage-gated potassium channels activate T cell integrin function: Physical and functional association between Kv1.3 channels and β1 integrins. J Exp Med 2000;191:1167–1176.
- Artym VV, Petty HR: Molecular proximity of Kv1.3 voltage-gated potassium channels and beta(1)-integrins on the plasma membrane of melanoma cells: Effects of cell adherence and channel blockers. J Gen Physiol 2002;120:29–38.
- Schwartz MA: Spreading of human endothelial cells on fibronectin or vitronectin triggers elevation of intracellular free calcium. J Cell Biol 1993;120:1003–1010.
- Bhattacharya S, Ying X, Fu C, Patel R, Kuebler W, Greenberg S, Bhattacharya J: Alpha(v)beta(3) integrin induces tyrosine phosphorylation-dependent Ca(2+) influx in pulmonary endothelial cells. Circ Res 2000;86:456–462.
Kawasaki J, Nurkiewicz TR, Davis MJ: Regulation of endothelial cell calcium current by αvβ3 integrin. FASEB J 2001;15:A109.
- Bhattacharya S, Fu C, Bhattacharya J, Greenberg S: Soluble ligands of the alpha v beta 3 integrin mediate enhanced tyrosine phosphorylation of multiple proteins in adherent bovine pulmonary artery endothelial cells. J Biol Chem 1995;270:16781–16787.
- Russell FD, Skepper JN, Davenport AP: Human endothelial cell storage granules: A novel intracellular site for isoforms of the endothelin-converting enzyme. Circ Res 1998;83:314–321.
Quayle JM, McCarron JG, Brayden JE, Nelson MT: Inward rectifier K+ currents in smooth muscle cells from rat resistance-sized cerebral arteries. Am J Physiol 1993;265:C1363–C1370.
Knot HJ, Nelson MT: Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries. Am J Physiol 1995;269:H348–H355.
- Harder DR, Narayanan J, Gebremedhin D, Roman RJ: Transduction of physical force by the vascular wall: Role of phospholipase C and cytochrome P450 metabolites of arachidonic acid. Trends Cardiovasc Med 1995;5:7–14.
Nelson MT, Patlak JB, Worley JF, Standen NB: Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am J Physiol 1990;259:C3–C18.
Platts SH, Mogford JE, Davis MJ, Meininger GA: Role of K+ channels in arteriolar vasodilation mediated by integrin interaction with RGD-containing peptide. Am J Physiol 1998;275:H1449–H1454.
- Miyamoto S, Akiyama SK, Yamada KM: Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science 1995;267:883–885.
- Wijetunge S, Lymn JS, Hughes AD: Effect of inhibition of tyrosine phosphatases on voltage-operated calcium channel currents in rabbit isolated ear artery cells. Br J Pharmacol 1998;124:307–316.
- Wijetunge S, Hughes AD: pp60c-src increases voltage-operated calcium channel currents in vascular smooth muscle cells. Biochem Biophys Res Commun 1995;217:1039–1044.
- Wijetunge S, Hughes AD: Activation of endogenous c-Src or a related tyrosine kinase by intracellular (pY)EEI peptide increases voltage-operated calcium channel currents in rabbit ear artery cells. FEBS Lett 1996;399:63–66.
- Hu XQ, Singh N, Mukhopadhyay D, Akbarali HI: Modulation of voltage-dependent Ca2+ channels in rabbit colonic smooth muscle cells by c-Src and focal adhesion kinase. J Biol Chem 1998;273:5337–5342.
- Wijetunge S, Hughes AD: Effect of platelet-derived growth factor on voltage-operated calcium channels in rabbit isolated ear artery cells. Br J Pharmacol 1995;115:534–538.
- Blair LA, Marshall J: IGF-1 modulates N and L calcium channels in a PI 3-kinase-dependent manner. Neuron 1997;19:421–429.
- Selinfreund RH, Blair LA: Insulin-like growth factor-I induces a rapid increase in calcium currents and spontaneous membrane activity in clonal pituitary cells. Mol Pharmacol 1994;45:1215–1220.
Bence-Hanulec KK, Marshall J, Blair LA: Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of the α1 subunit on a specific tyrosine residue. Neuron 2000;27:121–131.
Gui P, Wilson E, Zamponi GW, Braun A, Davis GE, Davis MJ: Modulation of expressed L-type calcium channels by α5 β1 integrin requires tyrosine phosphorylation of α1c channel subunit. FASEB J 2002;16:A798.
- Gerhardstein BL, Gao T, Bunemann M, Puri TS, Adair A, Ma H, Hosey MM: Proteolytic processing of the C terminus of the alpha(1C) subunit of L-type calcium channels and the role of a proline-rich domain in membrane tethering of proteolytic fragments. J Biol Chem 2000;275:8556–8563.
- Wei X, Neely A, Lacerda AE, Olcese R, Stefani E, Perez-Reyes E, Birnbaumer L: Modification of Ca2+ channel activity by deletions at the carboxyl terminus of the cardiac alpha 1 subunit. J Biol Chem 1994;269:1635–1640.
D’Angelo G, Mogford JE, Davis GE, Davis MJ, Meininger GA: Integrin-mediated reduction in vascular smooth muscle [Ca2+]i induced by RGD-containing peptide. Am J Physiol 1997;272:H2065–H2070.
- Wildering WC, Lodder JC, Kits KS, Bulloch AG: Nerve growth factor (NGF) acutely enhances high-voltage-activated calcium currents in molluscan neurons. J Neurophysiol 1995;74:2778–2781.
- Eliceiri BP, Cheresh DA: Adhesion events in angiogenesis. Curr Opin Cell Biol 2001;13:563–568.
- Jones PL, Crack J, Rabinovitch M: Regulation of tenascin-C, a vascular smooth muscle cell survival factor that interacts with the alpha v beta 3 integrin to promote epidermal growth factor receptor phosphorylation and growth. J Cell Biol 1997;139:279–293.
- Jones PL, Jones FS, Zhou B, Rabinovitch M: Induction of vascular smooth muscle cell tenascin-C gene expression by denatured type I collagen is dependent upon a β3 integrin-mediated mitogen-activated protein kinase pathway and a 122-base pair promoter element. J Cell Sci 1999;112:435–445.
- Jones FS, Jones PL: The tenascin family of ECM glycoproteins: Structure, function, and regulation during embryonic development and tissue remodeling. Dev Dyn 2000;218:235–259.
- Chiquet M: Regulation of extracellular matrix gene expression by mechanical stress. Matrix Biol 1999;18:417–426.
- Leung DY, Glagov S, Mathews MB: Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. Science 1976;191:475–477.
- Tyagi SC: Physiology and homeostasis of extracellular matrix: Cardiovascular adaptation and remodeling. Pathophysiology 2000;7:177–182.
- Hou G, Mulholland D, Gronska MA, Bendeck MP: Type VIII collagen stimulates smooth muscle cell migration and matrix metalloproteinase synthesis after arterial injury. Am J Pathol 2000;156:467–476.
- Bendeck MP, Irvin C, Reidy M, Smith L, Mulholland D, Horton M, Giachelli CM: Smooth muscle cell matrix metalloproteinase production is stimulated via alpha(v)beta(3) integrin. Arterioscler Thromb Vasc Biol 2000;20:1467–1472.
- Jian B, Jones PL, Li Q, Mohler ER 3rd, Schoen FJ, Levy RJ: Matrix metalloproteinase-2 is associated with tenascin-C in calcific aortic stenosis. Am J Pathol 2001;159:321–327.
- Faull RJ, Kovach NL, Harlan JM, Ginsberg MH: Affinity modulation of integrin alpha 5 beta 1:regulation of the functional response by soluble fibronectin. J Cell Biol 1993;121:155–162.
- Byzova TV, Rabbani R, D’Souza SE, Plow EF: Role of integrin alpha(v)beta3 in vascular biology. Thromb Haemost 1998;80:726–734.
- DiPersio CM, Trevithick JE, Hynes RO: Functional comparison of the α3A and α3B cytoplasmic domain variants of the chicken α3 integrin subunit. Exp Cell Res 2001;268:45–60.
- Retta SF, Balzac F, Ferraris P, Belkin AM, Fassler R, Humphries MJ, De Leo G, Silengo L, Tarone G: β1-integrin cytoplasmic subdomains involved in dominant negative function. Mol Biol Cell 1998;9:715–731.
- Pankov R, Cukierman E, Katz BZ, Matsumoto K, Lin DC, Lin S, Hahn C, Yamada KM: Integrin dynamics and matrix assembly: Tensin-dependent translocation of alpha(5)beta(1) integrins promotes early fibronectin fibrillogenesis. J Cell Biol 2000;148:1075–1090.
- Barillari G, Albonici L, Incerpi S, Bogetto L, Pistritto G, Volpi A, Ensoli B, Manzari V: Inflammatory cytokines stimulate vascular smooth muscle cells locomotion and growth by enhancing α5β1 integrin expression and function. Atherosclerosis 2001;154:377–385.
- Doi M, Shichiri M, Yoshida M, Marumo F, Hirata Y: Suppression of integrin alpha(v) expression by endothelin-1 in vascular smooth muscle cells. Hypertens Res 2000;23:643–649.
- Silletti S, Kessler T, Goldberg J, Boger DL, Cheresh DA: Disruption of matrix metalloproteinase 2 binding to integrin αvβ3 by an organic molecule inhibits angiogenesis and tumor growth in vivo. Proc Natl Acad Sci USA 2001;98:119–124.
Yan L, Moses MA, Huang S, Ingber DE: Adhesion-dependent control of matrix metalloproteinase-2 activation in human capillary endothelial cells. J Cell Sci 2000;113(pt 22):3979–3987.
- Bendeck MP, Nakada MT: The β3 integrin antagonist m7E3 reduces matrix metalloproteinase activity and smooth muscle cell migration. J Vasc Res 2001;38:590–599.
- Nakamura T, Ruiz-Lozano P, Lindner V, Yabe D, Taniwaki M, Furukawa Y, Kobuke K, Tashiro K, Lu Z, Andon NL, Schaub R, Matsumori A, Sasayama S, Chien KR, Honjo T: DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries. J Biol Chem 1999;274:22476–22483.
Medhora MM: Retinoic acid upregulates beta(1)-integrin in vascular smooth muscle cells and alters adhesion to fibronectin (in process citation). Am J Physiol 2000;279:H382–H387.
- Horwitz AR, Parsons JT: Cell migration – Movin’ on. Science 1999;286:1102–1103.
- Smilenov LB, Mikhailov A, Pelham RJ, Marcantonio EE, Gundersen GG: Focal adhesion motility revealed in stationary fibroblasts. Science 1999;286:1172–1174.
- Laser M, Willey CD, Jiang W, Cooper G 4th, Menick DR, Zile MR, Kuppuswamy D: Integrin activation and focal complex formation in cardiac hypertrophy. J Biol Chem 2000;275:35624–35630.
- Schoenwaelder SM, Burridge K: Bidirectional signaling between the cytoskeleton and integrins. Curr Opin Cell Biol 1999;11:274–286.
- Mould AP, Akiyama SK, Humphries MJ: Regulation of integrin alpha 5 beta 1-fibronectin interactions by divalent cations. Evidence for distinct classes of binding sites for Mn2+, Mg2+, and Ca2+. J Biol Chem 1995;270:26270–26277.
- Shyy JY, Chien S: Role of integrins in cellular responses to mechanical stress and adhesion. Curr Opin Cell Biol 1997;9:707–713.
- Turley EA: Extracellular matrix remodeling: Multiple paradigms in vascular disease. Circ Res 2001;88:2–4.
- Yee KO, Schwartz SM: Why atherosclerotic vessels narrow: The fibrin hypothesis. Thromb Haemost 1999;82:762–771.
- Lee RT, Berditchevski F, Cheng GC, Hemler ME: Integrin-mediated collagen matrix reorganization by cultured human vascular smooth muscle cells. Circ Res 1995;76:209–214.
- Gotwals PJ, Chi-Rosso G, Lindner V, Yang J, Ling L, Fawell SE, Koteliansky VE: The α1β1 integrin is expressed during neointima formation in rat arteries and mediates collagen matrix reorganization. J Clin Invest 1996;97:2469–2477.
- Corbett SA, Schwarzbauer JE: β3 integrin activation improves αvβ3-mediated retraction of fibrin matrices. J Surg Res 1999;83:27–31.
- Kawano K, Kantak SS, Murai M, Yao CC, Kramer RH: Integrin α3β1 engagement disrupts intercellular adhesion. Exp Cell Res 2001;262:180–196.
- Whittard JD, Akiyama SK: Activation of beta1 integrins induces cell-cell adhesion. Exp Cell Res 2001;263:65–76.
- Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi M: Increased expression of basement membrane components in human endothelial cells cultured in high glucose. J Clin Invest 1988;82:735–738.
- Roth T, Podesta F, Stepp MA, Boeri D, Lorenzi M: Integrin overexpression induced by high glucose and by human diabetes: Potential pathway to cell dysfunction in diabetic microangiopathy. Proc Natl Acad Sci USA 1993;90:9640–9644.
- Bezie Y, Lamaziere JM, Laurent S, Challande P, Cunha RS, Bonnet J, Lacolley P: Fibronectin expression and aortic wall elastic modulus in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol 1998;18:1027–1034.
- Intengan HD, Schiffrin EL: Structure and mechanical properties of resistance arteries in hypertension: Role of adhesion molecules and extracellular matrix determinants. Hypertension 2000;36:312–318.
- Brownlee M: Negative consequences of glycation. Metabolism 2000;49:9–13.
- Vlassara H, Palace MR: Diabetes and advanced glycation endproducts. J Intern Med 2002;251:87–101.
- Regoli M, Bendayan M: Alterations in the expression of the alpha 3 beta 1 integrin in certain membrane domains of the glomerular epithelial cells (podocytes) in diabetes mellitus. Diabetologia 1997;40:15–22.
- Intengan HD, Thibault G, Li JS, Schiffrin EL: Resistance artery mechanics, structure, and extracellular components in spontaneously hypertensive rats: Effects of angiotensin receptor antagonism and converting enzyme inhibition. Circulation 1999;100:2267–2275.
- Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986.
- UK Prospective Diabetes Study (UKPDS) Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–853.
Sheetz MJ, King GL: Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA 2002;288:2579–2588.
Ayo SH, Radnik RA, Glass WF 2nd, Garoni JA, Rampt ER, Appling DR, Kreisberg JI: Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium. Am J Physiol 1991;260:F185–F191.
- Stitt A, Gardiner TA, Alderson NL, Canning P, Frizzell N, Duffy N, Boyle C, Januszewski AS, Chachich M, Baynes JW, Thorpe SR, Anderson NL: The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes 2002;51:2826–2832.
- Kuzuya M, Asai T, Kanda S, Maeda K, Cheng XW, Iguchi A: Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice. Diabetologia 2001;44:433–436.
- Hill MA, Ege EA: Active and passive mechanical properties of isolated arterioles from STZ-induced diabetic rats. Effect of aminoguanidine treatment. Diabetes 1994;43:1450–1456.
- Wolffenbuttel BH, Boulanger CM, Crijns FR, Huijberts MS, Poitevin P, Swennen GN, Vasan S, Egan JJ, Ulrich P, Cerami A, Levy BI: Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 1998;95:4630–4634.
Yu G, Zou H, Prewitt RL, Hill MA: Impaired arteriolar mechanotransduction in experimental diabetes mellitus. J Diabetes Complications 1999;13:235–242.
- Kislinger T, Fu C, Huber B, Qu W, Taguchi A, Du Yan S, Hofmann M, Yan SF, Pischetsrieder M, Stern D, Schmidt AM: N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J Biol Chem 1999;274:31740–1749.
- Lander HM, Tauras JM, Ogiste JS, Hori O, Moss RA, Schmidt AM: Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. J Biol Chem 1997;272:17810–17814.
- Schmidt AM, Yan SD, Wautier JL, Stern D: Activation of receptor for advanced glycation end products: A mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 1999;84:489–497.
- Bishara NB, Dunlop ME, Murphy TV, Darby IA, Sharmini Rajanayagam MA, Hill MA: Matrix protein glycation impairs agonist-induced intracellular Ca2+ signaling in endothelial cells. J Cell Physiol 2002;193:80–92.
- Erb L, Liu J, Ockerhausen J, Kong Q, Garrad RC, Griffin K, Neal C, Krugh B, Santiago-Perez LI, Gonzalez FA, Gresham HD, Turner JT, Weisman GA: An RGD sequence in the P2Y(2) receptor interacts with alpha(V)beta(3) integrins and is required for G(o)-mediated signal transduction. J Cell Biol 2001;153:491–501.
- Short SM, Boyer JL, Juliano RL: Integrins regulate the linkage between upstream and downstream events in G protein-coupled receptor signaling to mitogen-activated protein kinase. J Biol Chem 2000;275:12970–12977.
- Nilius B, Droogmans G: Ion channels and their functional role in vascular endothelium. Physiol Rev 2001;81:1415–1459.
- Bishop GG, McPherson JA, Sanders JM, Hesselbacher SE, Feldman MJ, McNamara CA, Gimple LW, Powers ER, Mousa SA, Sarembock IJ: Selective alpha(v)beta(3)-receptor blockade reduces macrophage infiltration and restenosis after balloon angioplasty in the atherosclerotic rabbit. Circulation 2001;103:1906–1911.
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