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Mayo Clin Proc Innov Qual Outcomes. 2019 Feb 26;3(1):1-13. doi: 10.1016/j.mayocpiqo.2018.12.006. eCollection 2019 Mar.

Rethinking Endothelial Dysfunction as a Crucial Target in Fighting Heart Failure.

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Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL.
Department of Medicine, University of Chicago, Chicago, IL.
Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, FL.


Endothelial dysfunction is characterized by nitric oxide dysregulation and an altered redox state. Oxidative stress and inflammatory markers prevail, thus promoting atherogenesis and hypertension, important risk factors for the development and progression of heart failure. There has been a reemerging interest in the role that endothelial dysfunction plays in the failing circulation. Accordingly, patients with heart failure are being clinically assessed for endothelial dysfunction via various methods, including flow-mediated vasodilation, peripheral arterial tonometry, quantification of circulating endothelial progenitor cells, and early and late endothelial progenitor cell outgrowth measurements. Although the mechanisms underlying endothelial dysfunction are intimately related to cardiovascular disease and heart failure, it remains unclear whether targeting endothelial dysfunction is a feasible strategy for ameliorating heart failure progression. This review focuses on the pathophysiology of endothelial dysfunction, the mechanisms linking endothelial dysfunction and heart failure, and the various diagnostic methods currently used to measure endothelial function, ultimately highlighting the therapeutic implications of targeting endothelial dysfunction for the treatment of heart failure.


Ach, acetylcholine; CAD, coronary artery disease; CVD, cardiovascular disease; ECFC, endothelial colony-forming cell; EDHF, endothelium-derived hyperpolarizing factor; EPC, endothelial progenitor cell; EPC-CFU, EPC–colony-forming unit; FMD, flow-mediated vasodilation; H2O2, hydrogen peroxide; HF, heart failure; HFpEF, HF with preserved ejection fraction; HFrEF, HF with reduced ejection fraction; IVUS, intravascular ultrasound; LVEF, left ventricular ejection fraction; NO, nitric oxide; NOS, NO synthase; PAT, peripheral arterial tonometry; QCA, quantitative coronary angiography; ROS, reactive oxygen species; cGMP, cyclic guanosine monophosphate; eNOS, endothelial nitric oxide synthase

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