Krishnan Anirudh, Sharma Harman, Yuan Daniel, Trollope Alexandra F, Chilton Lisa
College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
J Cardiovasc Dev Dis. 2022 Jul 5;9(7):217. doi: 10.3390/jcdd9070217.
Cardiovascular diseases (CVDs) are a significant burden globally and are especially prevalent in obese and/or diabetic populations. Epicardial adipose tissue (EAT) surrounding the heart has been implicated in the development of CVDs as EAT can shift from a protective to a maladaptive phenotype in diseased states. In diabetic and obese patients, an elevated EAT mass both secretes pro-fibrotic/pro-inflammatory adipokines and forms intramyocardial fibrofatty infiltrates. This narrative review considers the proposed pathophysiological roles of EAT in CVDs. Diabetes is associated with a disordered energy utilization in the heart, which promotes intramyocardial fat and structural remodeling. Fibrofatty infiltrates are associated with abnormal cardiomyocyte calcium handling and repolarization, increasing the probability of afterdepolarizations. The inflammatory phenotype also promotes lateralization of connexin (Cx) proteins, undermining unidirectional conduction. These changes are associated with conduction heterogeneity, together creating a substrate for atrial fibrillation (AF). EAT is also strongly implicated in coronary artery disease (CAD); inflammatory adipokines from peri-vascular fat can modulate intra-luminal homeostasis through an "outside-to-inside" mechanism. EAT is also a significant source of sympathetic neurotransmitters, which promote progressive diastolic dysfunction with eventual cardiac failure. Further investigations on the behavior of EAT in diabetic/obese patients with CVD could help elucidate the pathogenesis and uncover potential therapeutic targets.
心血管疾病（CVDs）是全球范围内的一项重大负担，在肥胖和/或糖尿病患者中尤为普遍。心脏周围的心外膜脂肪组织（EAT）与心血管疾病的发生有关，因为在疾病状态下，EAT可从保护性表型转变为适应不良表型。在糖尿病和肥胖患者中，EAT质量增加不仅会分泌促纤维化/促炎脂肪因子，还会形成心肌内纤维脂肪浸润。这篇叙述性综述探讨了EAT在心血管疾病中所提出的病理生理作用。糖尿病与心脏能量利用紊乱有关，这会促进心肌内脂肪堆积和结构重塑。纤维脂肪浸润与心肌细胞钙处理和复极化异常有关，增加了后去极化的可能性。炎症表型还会促进连接蛋白（Cx）蛋白的侧向化，破坏单向传导。这些变化与传导异质性有关，共同为心房颤动（AF）创造了条件。EAT也与冠状动脉疾病（CAD）密切相关；血管周围脂肪产生的炎症脂肪因子可通过“由外及内”机制调节管腔内稳态。EAT也是交感神经递质的重要来源，可促进进行性舒张功能障碍并最终导致心力衰竭。对患有心血管疾病的糖尿病/肥胖患者中EAT行为的进一步研究，可能有助于阐明发病机制并发现潜在的治疗靶点。
