Mitochondrial Mechanisms in Cerebral Vascular Control: Shared Signaling Pathways with PreconditioningBusija D.W. · Katakam P.V.
Department of Pharmacology, Tulane University School of Medicine, New Orleans, La., USA
Mitochondrial-initiated events protect the neurovascular unit against lethal stress via a process called preconditioning, which independently promotes changes in cerebrovascular tone through shared signaling pathways. Activation of adenosine triphosphate (ATP)-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels) is a specific and dependable way to induce protection of neurons, astroglia, and cerebral vascular endothelium. Through the opening of mitoKATP channels, mitochondrial depolarization leads to activation of protein kinases and transient increases in cytosolic calcium (Ca2+) levels that activate terminal mechanisms that protect the neurovascular unit against lethal stress. The release of reactive oxygen species from mitochondria has similar protective effects. Signaling elements of the preconditioning pathways also are involved in the regulation of vascular tone. Activation of mitoKATP channels in cerebral arteries causes vasodilation, with cell-specific contributions from the endothelium, vascular smooth muscles, and nerves. Preexisting chronic conditions, such as insulin resistance and/or diabetes, prevent preconditioning and impair relaxation to mitochondrial-centered responses in cerebral arteries. Surprisingly, mitochondrial activation after anoxic or ischemic stress appears to protect cerebral vascular endothelium and promotes the restoration of blood flow; therefore, mitochondria may represent an important, but underutilized target in attenuating vascular dysfunction and brain injury in stroke patients.
© 2014 S. Karger AG, Basel
Received: October 14, 2013
Accepted after revision: February 19, 2014
Published online: May 22, 2014
Number of Print Pages : 15
Number of Figures : 7, Number of Tables : 0, Number of References : 133
Journal of Vascular Research (Incorporating 'International Journal of Microcirculation')
Vol. 51, No. 3, Year 2014 (Cover Date: August 2014)
Journal Editor: Pohl U. (Munich), Meininger G.A. (Columbia, Mo.)
ISSN: 1018-1172 (Print), eISSN: 1423-0135 (Online)
For additional information: http://www.karger.com/JVR