Newsletter Issue: April 2016

From the Laboratories of MCS Members: Recent Studies in Microcirculation*

from Volume 23 Issue 1 -  (pages 15-32)

Endothelium-Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions

Featuring: David Ellinsworth (University of Bristol), Shaun Sandow (University of New South Wales), and David Gutterman (Medical College of Wisconsin)

A growing number of clinical studies indicate that coronary microvascular disease precedes coronary atherosclerosis and is a major independent risk factor for future adverse cardiac events. Our review attempts to cohesively integrate a complex series of findings from a broad range of literature concerning microcirculatory regulation in the human heart. By critically analyzing the hypothesis that dilator signaling pathways in coronary resistance arteries are organized into spatially discrete myoendothelial microdomains, we speculate on important future research directions that could potentially uncover novel therapeutic targets to improve myocardial perfusion, whilst also preventing chronic coronary artery disease progression.

Current and future research activities include defining ultrastructure-function relationships of myoendothelial signaling microdomains in human coronary arterioles (Sandow, Ellinsworth and Gutterman), in uterine radial arteries from women in normal and preeclamptic pregnancy (Sandow, Ellinsworth et al), and mechanisms of cerebral ischemic stroke (Sandow, Ellinsworth, et al.). Dr Gutterman is also investigating mechanisms that drive the transition in endothelium-derived mediators of vasodilation from nitric oxide to hydrogen peroxide in coronary artery disease, with recent work pointing to roles for ceramide and telomerase. We all are independently pursuing the molecular pharmacology of epoxyeicosatrienoic acid-transient receptor potential cation channel interactions and their roles in multiple organ/tissue physiology.

Read the abstract.