Publication
Title
Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction
Author
Abstract
OBJECTIVES The present study investigated whether systemic, low-grade inflammation of metabolic risk contributed to diastolic left ventricular (LV) dysfunction and heart failure with preseved ejection fraction (HFpEF) through coronary microvascular endothelial activation, which alters paracrine signalling to cardiomyocytes and predisposes them to hypertrophy and high diastolic stiffness. BACKGROUND Metabolic risk is associated with diastolic LV dysfunction and HFpEF. METHODS We explored inflammatory endothelial activation and its effects on oxidative stress, nitric oxide (NO) bioavailability, and cyclic guanosine monophosphate (cGMP)-protein kinase G (KG) signalling in myocardial biopsies of HFpEF patients and validated our findings by comparing obese Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1)-I-IFpEF rats to ZSF1-Control (Ctrl) rats. RESULTS In myocardium of HFpEF patients and Z5F1-HFpEF rats, we observed the following: 1) E-selectin and intercellular adhesion molecule-1 expression levels were upregulated; 2) NADPH oxidase 2 expression was raised in macrophages and endothelial cells but not in cardiomyocytes; and 3) uncoupling of endothelial nitric oxide synthase, which was associated with reduced myocardial nitrite/nitrate concentration, cGMP content, and PKG activity. CONCLUSIONS HFpEF is associated with coronary microvascular endothelial activation and oxidative stress. These lead to a reduction of NO-dependent signalling from endothelial cells to cardiomyocytes, which can contribute to the high cardiomyocyte stiffness and hypertrophy observed in 1-IFpEF. (C) 2016 by the American College of Cardiology Foundation.
Language
English
Source (journal)
JACC: Heart Failure
Publication
2016
ISSN
2213-1779
Volume/pages
4:4(2016), p. 312-324
ISI
000373750600012
Full text (Publishers DOI)
Full text (publishers version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.05.2016
Last edited 30.04.2017
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