Mechanotransduction regulates inflammation responses of epicardial adipocytes in cardiovascular diseases

Abstract

Adipose tissue is a crucial regulator in maintaining cardiovascular homeostasis by secreting various bioactive products to mediate the physiological function of the cardiovascular system. Accumulating evidence shows that adipose tissue disorders contribute to several kinds of cardiovascular disease (CVD). Furthermore, the adipose tissue would present various biological effects depending on its tissue localization and metabolic statuses, deciding the individual cardiometabolic risk. Crosstalk between adipose and myocardial tissue is involved in the pathophysiological process of arrhythmogenic right ventricular cardiomyopathy (ARVC), cardiac fibrosis, heart failure, and myocardial infarction/atherosclerosis. The abnormal distribution of adipose tissue in the heart might yield direct and/or indirect effects on cardiac function. Moreover, mechanical transduction is critical for adipocytes in differentiation, proliferation, functional maturity, and homeostasis maintenance. Therefore, understanding the features of mechanotransduction pathways in the cellular ontogeny of adipose tissue is vital for underlining the development of adipocytes involved in cardiovascular disorders, which would preliminarily contribute positive implications on a novel therapeutic invention for cardiovascular diseases. In this review, we aim to clarify the role of mechanical stress in cardiac adipocyte homeostasis and its interplay with maintaining cardiac function.

Mechanobiology of Adipocytes

“…Several mechanoregulatory proteins have roles in adipocyte differentiation and function. Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional cofactors of the Hippo pathway that bind to the transcriptional enhanced associate domain (TEAD) family of transcriptional factors and are key regulators in the differentiation of mesenchymal stem cells (MSCs) [ 51 , 52 , 53 , 54 ]. The phosphorylation of YAP leads to its retention in the cytoplasm and its subsequent degradation, and these events are associated with an adipogenic phenotype ( Figure 2 ).…”

Targeting the Inflammatory Hallmarks of Obesity-Associated Osteoarthritis: Towards Nutraceutical-Oriented Preventive and Complementary Therapeutic Strategies Based on n-3 Polyunsaturated Fatty Acids

“…showed that RvD1 activates anti-inflammatory molecules in synoviocytes by activating Hippo-YAP signalling pathway, thus leading to YAP cytoplasmic sequestration and proteasomal degradation [123]. Notably, this is of great interest in the context of OA, given that the inhibition of YAP has been proposed as a mechanism to prevent OA development [125], and in Ob, given that it is increased in response to these mechanical changes in hypertrophic adipocytes [126].…”

Effects of Mechanical Stress on Endothelial Cells In Situ and In Vitro

“…On the other hand, cytokines and growth factors can influence how cells respond to mechanical stress. By controlling the synthesis and function of mechanosensors, cytoskeletal elements, and integrins, they can modify the receptivity of endothelial cells to mechanical stimuli [237][238][239].…”

“…In hypertension-related endothelial dysfunction, NO bioavailability is reduced, oxidative stress is increased, inflammatory processes are triggered, and the endothelial barrier function is impaired. According to Liu et al [239] and Gallo et al [254], these changes lead to vasoconstriction, increased vascular tone, and decreased vasodilation, contributing to the maintenance of hypertension.…”