Potential role of the microvasculature in progression of heart failure.
After cardiac injury, there are changes in the cardiac myocyte morphology, function, matrix, and molecular gene expression. These all play an important role in remodeling of the injured heart, contributing to the progression toward heart failure. The role of the microvasculature in the progression toward heart failure is less well characterized. However, laboratory studies have established that there are important interactions between the microvascular endothelium and the myocyte. Furthermore, in a multitude of animal models of heart failure and cardiomyopathy, there is always an association with microvascular abnormalities. Reversal of these abnormalities is also associated with improvement in the cardiomyopathy. Major mediators that likely play an important role in the microvasculature include endothelin and nitric oxide. These are elaborated by both endothelium and myocyte compartments of the myocardium. Preliminary clinical studies already demonstrate that microvascular ischemia may have prognostic power in patients with nonischemic dilated cardiomyopathy. Results from these studies showed a reduction in mortality from treatment with amlodipine, suggesting a possible benefit based on changes in the microvasculature.
Liu
P P
PP
Toronto General Hospital, University of Toronto, Ontario, Canada.
Mak
S
S
Stewart
D J
DJ
D017311:Amlodipine / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D008833:Microcirculation; D009206:Myocardium / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
D002121:Calcium Channel Blockers; D016232:Endothelins; D017311:Amlodipine; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II