Plasminogen Activator Expression Correlates with Genetic Differences in Vascular RemodelingKorshunov V.A. · Solomatina M.A. · Plekhanova O.S. · Parfyonova Y.V. · Tkachuk V.A. · Berk B.C.
aCenter for Cardiovascular Research, Aab Institute of Biomedical Sciences and Department of Medicine, University of Rochester, Rochester, N.Y., USA; bMolecular Endocrinology Laboratory, Institute of Experimental Cardiology, Russian Cardiology Research and Production Center, and cMoscow State University, Moscow, Russia
Intima-media thickening (IMT) of the carotid artery, a form of vascular remodeling, correlates well with coronary artery disease risk in humans. Vascular remodeling in response to blood flow is a complex process that critically involves altered cell matrix interactions. To gain insight into these events, we performed partial carotid ligation (left carotid (LCA) = low flow and right carotid (RCA) = high flow) in 2 inbred mouse strains: C57Bl/6J (C57) and FVB/NJ (FVB). To evaluate the role of the 2 major matrix-degrading systems, plasminogen activators (PAs) and matrix metalloproteinases (MMPs), we compared the expression of u-PA, t-PA, MMP-2 and MMP-9 in ligated carotids of C57 and FVB mice. The extent of remodeling was greater in response to low LCA than high RCA flow. Despite a similar decrease in LCA flow in both strains, maximal IMT volume was greater in FVB (82 ± 7 × 10–6 µm3) than in C57 (38 ± 4 × 10–6 µm3) after ligation. Among PAs and MMPs, increased expression of t-PA and u-PA correlated with increased IMT (p < 0.0005 and p < 0.001, respectively). MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-2 expression also increased, but did not differ between strains. In summary, flow-induced IMT of the carotid is genetically determined and correlates with t-PA and u-PA expression in 2 inbred mouse strains.
Bradford C. Berk, MD, PhD
University of Rochester, Center for Cardiovascular Research
601 Elmwood Ave, Rochester, NY 14642 (USA)
Tel. +1 585 273 1946, Fax +1 585 273 1497
Received: May 25, 2004
Accepted after revision: July 30, 2004
Published online: October 28, 2004
Number of Print Pages : 10
Number of Figures : 6, Number of Tables : 4, Number of References : 31
Journal of Vascular Research (Incorporating International Journal of Microcirculation)
Vol. 41, No. 6, Year 2004 (Cover Date: November-December 2004)
Journal Editor: U. Pohl, Munich; G.A. Meininger, College Station, Tex.
ISSN: 1018–1172 (print), 1423–0135 (Online)
For additional information: http://www.karger.com/jvr