GENETIC ANALYSIS OF SMOOTH MUSCLE PHENOTYPE IN ARTERIALIZED CAPILLARIES

FUNCTIONAL VASODILATION IS IMPAIRED IN ARTERIALIZED CAPILLARIES IN THE SPINOTRAPEZIUS Joshua Cutts Ischemic diseases are the result of atherosclerotic plaques, which occlude conduit arteries. Ischemic disease in different tissues leads to different diseases such as coronary artery disease(CHD), cerebrovascular disease (CVD), and peripheral artery disease (PAD). Patient vasculature architecture is variable; some patients have many collateral vessels, which connect one arterial branch to another, and readily serve as natural bypass routes to atherosclerotic occlusions. Following occlusion they enlarge and provide blood flow to tissue distal. Patients with many natural collateral vessels are ischemia protected, unfortunately not all patients have collateral arterioles available to remodel into conduit vessels and provide blood flow to distal tissue. It would therefore be advantageous to stimulate the arterialization of collateral capillaries, capillaries that connect adjacent arterial branches, to form conduit collaterals. Unfortunately just having a robust collateral network is not sufficient to provide effective revascularization, it requires that collaterals have the ability to regulate blood flow, which is hypothesized to be impaired during collateral growth. The reactivity of arterialized capillaries, is significantly impaired (2% ± 2% vs. 29% ± 12% p<0.05) when compared to sham operated terminal arterioles of a similar diameter at day 7. But by day 21 this ability to vasodilate is restored. (167% ± 17% vs 81% ± 13% p> 0.05) Thus, arterialized capillaries are unable to efficiently regulate blood flow in response to endogenous muscle stimulation. Ineffective regulation of blood flow could be caused by a synthetic smooth muscle cell phenotype in nascent arterialized capillaries. This phenotype is proliferative and therefore unable to regulate tension in contrast to a contractile phenotype, which can regulate its contractile state, and therefore the diameter arterioles. Genetic analysis was performed to examine this hypothesis. It was found that areas of putative arterialized capillaries had increased expression of both synthetic and contractile smooth muscle cells. These experiments provide some support for the hypothesis that impaired function of arterialized capillaries is due to a synthetic phenotype but also demonstrates the need for more work to be done to more thoroughly examine the cause of observed impaired vasodilation in arterialized capillaries. ACKNOWLEDGEMENTS I’d like to thank Trevor Cardinal for giving me the opportunity to pursue research and pushing me to succeed. His trust and support have shaped my life in more ways than I could have ever imagined and for that I will be forever grateful. I’d also like to thank my entire family for all their support and love. Without them none of the work I’ve done would have been possible. Finally I’d like to thank the past and present members of the microcirculation and vascular regeneration lab for everything from initial training, experimental troubleshooting, and becoming some of my best friends. “In the middle of difficulty lies opportunity. ” -Albert Einstein Table of