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Title: Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy
Authors: Wang, L
Cai, Y 
Jian, L
Cheung, CW
Zhang, L
Xia, Z
Issue Date: 4-Jan-2021
Source: Cardiovascular diabetology, 4 Jan, 2021, v. 20, 2, p. 1-15
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.
Keywords: Diabetic cardiomyopathy
PPARα modulator
Metformin
Glucagon-like peptide 1-receptor agonists
Sodium–glucose co-transporter type 2 inhibitors
Publisher: BioMed Central
Journal: Cardiovascular diabetology 
EISSN: 1475-2840
DOI: 10.1186/s12933-020-01188-0
Rights: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
The following publication Wang, L., Cai, Y., Jian, L. et al. Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy. Cardiovasc Diabetol 20, 2 (2021) is available at https://doi.org/10.1186/s12933-020-01188-0
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