Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy

Abstract

The prevalence of cardiomyopathy is higher in diabetic patients than those without diabetes. Diabetic cardiomyopathy (DCM) is defined as a clinical condition of abnormal myocardial structure and performance in diabetic patients without other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease. Multiple molecular events contribute to the development of DCM, which include the alterations in energy metabolism (fatty acid, glucose, ketone and branched chain amino acids) and the abnormalities of subcellular components in the heart, such as impaired insulin signaling, increased oxidative stress, calcium mishandling and inflammation. There are no specific drugs in treating DCM despite of decades of basic and clinical investigations. This is, in part, due to the lack of our understanding as to how heart failure initiates and develops, especially in diabetic patients without an underlying ischemic cause. Some of the traditional anti-diabetic or lipid-lowering agents aimed at shifting the balance of cardiac metabolism from utilizing fat to glucose have been shown inadequately targeting multiple aspects of the conditions. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, plays an important role in mediating DCM-related molecular events. Pharmacological targeting of PPARα activation has been demonstrated to be one of the important strategies for patients with diabetes, metabolic syndrome, and atherosclerotic cardiovascular diseases. The aim of this review is to provide a contemporary view of PPARα in association with the underlying pathophysiological changes in DCM. We discuss the PPARα-related drugs in clinical applications and facts related to the drugs that may be considered as risky (such as fenofibrate, bezafibrate, clofibrate) or safe (pemafibrate, metformin and glucagon-like peptide 1-receptor agonists) or having the potential (sodium–glucose co-transporter 2 inhibitor) in treating DCM.

Plasma Lipidomics Identifies Unique Lipid Signatures and Potential Biomarkers for Patients With Aortic Dissection

“…LPCs can be acylated and deacylated by lysophospholipid acyltransferases and phospholipases to generate PCs and release FAs, respectively, thus affecting the pathogenesis of AD. Additionally, LPCs can acts as the ligands to activate peroxisome proliferator-activated receptors, which are commonly used as the targets for treating metabolic diseases, such as diabetes and cardiovascular diseases (32,33). The decreases in LPCs in patients with AD in this study were consistent with their mediatory roles in the expression of peroxisome proliferatoractivated receptors (31).…”

SGLT1 Knockdown Attenuates Cardiac Fibroblast Activation in Diabetic Cardiac Fibrosis

“…Diabetic cardiomyopathy (DCM) is a myocardial disease that is specific to patients with diabetes and is independent of various types of heart diseases, including hypertension, coronary, and valvular ( Bugger and Abel, 2014 ; Seferovic and Paulus, 2015 ). Cardiac fibrosis caused by abnormal glucose metabolism and microangiopathy are the main pathological features of DCM, leading to impairment of cardiac function and eventual progression to heart failure ( Wang et al, 2021 ). The activation of cardiac fibroblasts (CFs) and degeneration of cardiomyocytes provide the biological basis for cardiac remodeling and the pathophysiological basis of DCM formation ( Zhang et al, 2020 ).…”

Activation of PPARα by Fenofibrate Attenuates the Effect of Local Heart High Dose Irradiation on the Mouse Cardiac Proteome

“…The beneficial effects of PPAR ligands have been demonstrated on various cardiovascular risk factors [ 42 , 43 , 44 , 45 ]. Agonist activation of PPARα has been shown to protect against acute myocardial ischemia [ 46 ], myocardial remodeling and hypertension [ 47 ], hypertrophy [ 48 ], diabetic cardiomyopathy [ 49 ], atherogenesis [ 50 ] and vascular injury [ 44 ]. The outcome profiles of clinical trials using different PPARα agonists were not consistently similar.…”