Adiponectin Signaling Dysfunction and Pro-inflammation in Perivascular Adipose Tissue in Non-obstructive Ischemic Heart Disease: A Narrative Literature Review of New Endocrine-Metabolic Therapeutic Targets
Abstract
Ischemia with non-obstructive coronary arteries (INOCA)/myocardial infarction with non-obstructive coronary arteries (MINOCA) affects a substantial proportion of patients undergoing coronary angiography; however, its pathophysiology remains incompletely understood, and evidence-based management remains limited. This narrative review synthesizes mechanistic, translational, and clinical evidence linking pericoronary perivascular adipose tissue (PVAT) dysfunction to coronary microvascular dysfunction (CMD) and vasomotor dysregulation in the absence of epicardial stenosis. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, the Cochrane Library, and Google Scholar up to March 2025, encompassing preclinical studies, observational cohorts, imaging studies, and clinical trials across five thematic domains: PVAT physiology, adiponectin signaling, PVAT phenotypic transition in INOCA/MINOCA, pericoronary fat attenuation index (FAI), and endocrine-metabolic therapeutic targets. In healthy individuals, PVAT maintains coronary homeostasis through adiponectin-mediated AMP-activated protein kinase (AMPK)-endothelial nitric oxide synthase (eNOS)-nitric oxide signaling and anti-inflammatory paracrine effects. Under metabolic dysfunction, PVAT undergoes a phenotypic transition characterized by reduced adiponectin secretion and increased production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species, thereby impairing…
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