Flow-induced coronary vasospasm in diabetic patients

Project: Research project

Description

DESCRIPTION (provided by applicant): Patients with type 2 diabetes mellitus (T2-DM) have higher prevalence of no-reflow phenomenon - a poorly understood and unpredictable complication of percutaneous coronary intervention (PCI) in which diminished blood flow to distal microvascular beds persists despite the successful treatment of the occlusive lesion of the epicardial coronary artery. Current therapeutic interventions to prevent no reflow are ineffective. Preliminary observations related to this application led to my main hypothesis that small coronary arteries of diabetic patients exhibit a paradoxical constriction to sudden increases in flow, an alteration, which contributes to no reflow. I propose that RhoA-dependent co-localization of arginase I and eNOS leads to reduced NO synthesis and diminished NO-mediated dilatation in response to flow in T2-DM. I also hypothesize that stimulation of platelet endothelium cell adhesion molecule -1 (Pecam-1, known as primary flow sensor in endothelium) with increases in intraluminal flow elevates endothelial [Ca2+]i, which via inducing phospholipase A2 and arachidonic acid release leads to enhanced production of thromboxane A2 in coronary vessels of T2-DM patients. To test these hypotheses, I aim to isolate small coronary vessels from the (discarded) atrial appendages of patients with T2-DM undergoing cardiac surgery. Using small vessel pressure myography and videomicroscopy, diameter changes of the isolated, coronary arteriole (
StatusFinished
Effective start/end date8/15/106/30/16

Funding

  • National Institutes of Health: $353,430.00
  • National Institutes of Health: $373,900.00
  • National Institutes of Health: $363,825.00
  • National Institutes of Health: $126,525.00
  • National Institutes of Health: $270,975.00
  • National Institutes of Health: $371,250.00

Fingerprint

Coronary Vasospasm
Type 2 Diabetes Mellitus
Coronary Vessels
Endothelium
Myography
No-Reflow Phenomenon
Arginase
Atrial Appendage
Video Microscopy
Thromboxane A2
Phospholipases A2
Cell Adhesion Molecules
Arterioles
Percutaneous Coronary Intervention
Arachidonic Acid
Constriction
Thoracic Surgery
Dilatation
Blood Platelets
Pressure

ASJC

  • Medicine(all)