GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hype...

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Bibliographic Details
Published in:International journal of biological sciences 2021-01, Vol.17 (8), p.2050-2068
Main Authors: Ma, Xiaoxuan, Liu, Zhenghong, Ilyas, Iqra, Little, Peter J, Kamato, Danielle, Sahebka, Amirhossein, Chen, Zhengfang, Luo, Sihui, Zheng, Xueying, Weng, Jianping, Xu, Suowen
Format: Article
Language:English
Subjects:
Agonists
Angina pectoris
Animal models
Arteriosclerosis
Atherosclerosis
Atherosclerosis - drug therapy
Atherosclerosis - metabolism
Blood pressure
Cardiomyocytes
Cardiovascular disease
Cardiovascular diseases
Cardiovascular Diseases - metabolism
Cardiovascular Diseases - prevention & control
Cell culture
Clinical trials
Congestive heart failure
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Disease prevention
Drug therapy
Endothelial cells
Glucagon
Glucagon-like peptide 1
Glucagon-Like Peptide-1 Receptor - agonists
Glucagon-Like Peptide-1 Receptor - metabolism
Glucose
Hemoglobin
Humans
Hypertension
Hypoglycemia
Hypoglycemic Agents - pharmacology
Inflammation
Insulin
Insulin secretion
Ischemia
Kinases
Lipids
Macrophages
Molecular modelling
Monocytes
Mortality
Muscles
Proteins
Receptors
Review
Risk factors
Side effects
Smooth muscle
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Summary:Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.59965