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Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study.

ABSTRACT: BACKGROUND:Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. METHODS:A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. RESULTS:During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p?

SUBMITTER: Zhang HW

PROVIDER: S-EPMC7011523 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study.

Zhang Hui-Wen HW Jin Jing-Lu JL Cao Ye-Xuan YX Liu Hui-Hui HH Zhang Yan Y Guo Yuan-Lin YL Wu Na-Qiong NQ Gao Ying Y Xu Rui-Xia RX Hua Qi Q Li Yan-Fang YF Cui Chuan-Jue CJ Liu Geng G Dong Qian Q Sun Jing J Li Jian-Jun JJ

Cardiovascular diabetology 20200210 1

<h4>Background</h4>Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM.<h4>Methods</h4>A total of 4594 patients with angiography-prove ...[more]

PMID: 32041617

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Project description:BackgroundEndothelial cells depend on glycolysis for much of their energy production. Impaired endothelial glycolysis has been associated with various vascular pathobiologies, including impaired angiogenesis and atherogenesis. IFN-γ (interferon-γ)-producing CD4+ and CD8+ T lymphocytes have been identified as the predominant pathological cell subsets in human atherosclerotic plaques. Although the immunologic consequences of these cells have been extensively evaluated, their IFN-γ-mediated metabolic effects on endothelial cells remain unknown. The purpose of this study was to determine the metabolic consequences of the T-lymphocyte cytokine, IFN-γ, on human coronary artery endothelial cells.MethodsThe metabolic effects of IFN-γ on primary human coronary artery endothelial cells were assessed by unbiased transcriptomic and metabolomic analyses combined with real-time extracellular flux analyses and molecular mechanistic studies. Cellular phenotypic correlations were made by measuring altered endothelial intracellular cGMP content, wound-healing capacity, and adhesion molecule expression.ResultsIFN-γ exposure inhibited basal glycolysis of quiescent primary human coronary artery endothelial cells by 20% through the global transcriptional suppression of glycolytic enzymes resulting from decreased basal HIF1α (hypoxia-inducible factor 1α) nuclear availability in normoxia. The decrease in HIF1α activity was a consequence of IFN-γ-induced tryptophan catabolism resulting in ARNT (aryl hydrocarbon receptor nuclear translocator)/HIF1β sequestration by the kynurenine-activated AHR (aryl hydrocarbon receptor). In addition, IFN-γ resulted in a 23% depletion of intracellular nicotinamide adenine dinucleotide in human coronary artery endothelial cells. This altered glucose metabolism was met with concomitant activation of fatty acid oxidation, which augmented its contribution to intracellular ATP balance by >20%. These metabolic derangements were associated with adverse endothelial phenotypic changes, including decreased basal intracellular cGMP, impaired endothelial migration, and a switch to a proinflammatory state.ConclusionsIFN-γ impairs endothelial glucose metabolism by altered tryptophan catabolism destabilizing HIF1, depletes nicotinamide adenine dinucleotide, and results in a metabolic shift toward increased fatty acid oxidation. This work suggests a novel mechanistic basis for pathological T lymphocyte-endothelial interactions in atherosclerosis mediated by IFN-γ, linking endothelial glucose, tryptophan, and fatty acid metabolism with the nicotinamide adenine dinucleotide balance and ATP generation and their adverse endothelial functional consequences.

Dataset Information

Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study.

Publications

Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study.

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