Between Inflammation and Autophagy: The Role of Leptin-Adiponectin Axis in Cardiac Remodeling

Abstract

Cardiac remodeling is the process by which the heart adapts to stressful stimuli, such as hypertension and ischemia/reperfusion; it ultimately leads to heart failure upon longterm exposure. Autophagy, a cellular catabolic process that was originally considered as a mechanism of cell death in response to detrimental stimuli, is thought to be one of the main mechanisms that controls cardiac remodeling and induces heart failure. Dysregulation of the adipokines leptin and adiponectin, which plays essential roles in lipid and glucose metabolism, and in the pathophysiology of the neuroendocrine and cardiovascular systems, has been shown to affect the autophagic response in the heart and to contribute to accelerate cardiac remodeling. The obesity-associated protein leptin is a pro-inflammatory, tumor-promoting adipocytokine whose elevated levels in obesity are associated with acute cardiovascular events, and obesity-related hypertension. Adiponectin exerts anti-inflammatory and antitumor effects, and its reduced levels in obesity correlate with the pathogenesis of obesityassociated cardiovascular diseases. Leptin-and adiponectin-induced changes in autophagic flux have been linked to cardiac remodeling and heart failure. In this review, we describe the different molecular mechanisms of hyperleptinemia-and hypoadiponectinemia-mediated pathogenesis of cardiac remodeling and the involvement of autophagy in this process. A better understanding of the roles of leptin, adiponectin, and autophagy in cardiac functions and remodeling, and the exact signal transduction pathways by which they contribute to cardiac diseases may well lead to discovery of new therapeutic agents for the treatment of cardiovascular remodeling.

Anthropometric measures and the risk of developing atrial fibrillation: a Swedish Cohort Study

“…As previously mentioned, obesity is also associated with increased pericardial tissue, which is a risk for structural changes within the heart that alter the cardiac electrical circuits, causing AF [ 30 ]. In addition, obesity–related hypertension as well as various obesity-related hormones, such as leptin, adiponectin and tumor necrosis factor α [ 31 ] could also be common links between obesity, cardiac remodeling and increased risk of AF [ 32 ].…”

PCSK9 and Other Metabolic Targets to Counteract Ischemia/Reperfusion Injury in Acute Myocardial Infarction and Visceral Vascular Surgery

“…Adipose tissue constitutes a central node in the inter-organ crosstalk network and mediates the regulation of multiple organs and tissues through adipokines (also called adipocytokines), which are biologically active molecules causing pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation [79,80]. Adipokines play an important role in regulating vascular tone [81]. For instance, the adipokines adiponectin, visfatin, omentin, and the unidentified adipocyte-derived relaxing factor (ADRF) exert vasorelaxing effects on the vascular wall [82].…”

“…Upon binding to T-cadherin, adiponectin has been shown to reduce ROS production, TNF-α levels, and to protect against myocardial I/R injury [84] by activating AMPK and COX-2, respectively, with anti-apoptotic and anti-inflammatory actions [81,85].…”

“…Leptin in a healthy state controls blood pressure by regulating sympathetic activitydependent vasoconstriction and the endothelial release of nitric oxide (NO), as well as Ang II-dependent vasoconstriction [83]. The physiological activity of leptin strongly depends on its binding to obesity receptors [81] as well as circulating leptin levels, which are positively correlated with circulating levels of PCSK9 in healthy individuals [86].…”

Aldehyde Dehydrogenase 2 (ALDH2) Elicits Protection against Pulmonary Hypertension via Inhibition of ERK1/2-Mediated Autophagy

“…Autophagy functions as a fundamental process in sustaining cellular homeostasis, and its dysregulation is associated with various cardiopulmonary diseases, including load-induced cardiac remodeling, ischemic cardiac remodeling, chronic obstructive pulmonary disease, and PH [ 21 ]. Nevertheless, the argument remains whether autophagy serves as a protecting or worsening process because both excessive and insufficient autophagy contributes to cell death [ 22 , 23 ]. Although some studies have reported that autophagy inhibition via deletion of the autophagic protein LC3B enhances hypoxia-induced PASMC proliferation [ 24 ], other studies have found that its pharmacological inhibition suppresses PASMC proliferation [ 25 ].…”