Antidiabetic drugs and oxidized low-density lipoprotein: A review of anti-atherosclerotic mechanisms. (October 2021)

• Record Type: Journal Article
• Authors: Ahmadi, Ali; Panahi, Yunes; Johnston, Thomas P.; Sahebkar, Amirhossein
• Is Part Of: Pharmacological research. Volume 172(2021)
• Publication Date: 2021-10
• Subjects: ABCA1 ATP-binding cassette transporter 1 -- ABCG1 ATP-binding cassette sub-family G member 1 -- ACAT1 acetyl-CoA acetyltransferase -- AGEs advanced glycation end products -- Akt protein kinase B -- AMPK AMP-activated protein kinase -- AP-1 activator protein-1 -- CAD coronary artery disease -- CVD cardiovascular disease -- DPP-4 dipeptidyl peptidase-4 -- ECs endothelial cells -- ELAM endothelial-leukocyte adhesion molecule -- eNOS endothelial nitric oxide synthetase -- ERK extracellular-regulated kinases -- ERS endoplasmic reticulum stress -- GIP gastric inhibitory polypeptide -- GLP-1 glucagon-like peptide-1 -- GLP-1RA glucagon-like peptide-1 receptor agonist -- HDL high-density lipoprotein -- ICAM-1 intercellular cell adhesion molecule -- IGF-1 insulin-like growth factor-1 -- IR insulin resistance -- JNK c-Jun N-terminal kinase -- KATP ATP-sensitive potassium channels, LDL, low-density lipoprotein -- LOX-1 lectin-like oxidized receptor-1 -- MAPK mitogen-activated protein kinase -- MCP-1 macrophage chemotactic protein-1 -- MDA-LDL malondialdehyde-low-density lipoprotein -- MI myocardial infarction -- MMP matrix metalloproteinase -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- NLRP3 NLR family pyrin domain-containing 3 -- NO nitric oxide -- oxLDL oxidized low-density lipoprotein -- PCOS polycystic ovary syndrome -- PIO pioglitazone -- PKC protein kinase C -- PPARγ peroxisome proliferator-activated receptor gamma -- PPG postprandial glucose -- RAGE receptor for advanced glycation end products -- ROS reactive oxygen species -- SGLT2 sodium-glucose cotransporter 2 -- SRA scavenger receptor A -- SUs sulfonylureas -- SURs sulfonylurea receptors -- T1DM type 1 diabetes mellitus -- T2DM type 2 diabetes mellitus -- TG triglyceride -- TNF-α Tumor necrosis factor-α -- TZDs thiazolidinediones -- VCAM-1 vascular cell adhesion molecule-1 -- VSMCs vascular smooth muscle cells; Atherosclerosis -- Cardiovascular disease -- Diabetes -- Oxidized LDL; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105819
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Cardiovascular disease is one of the leading causes of mortality globally. Atherosclerosis is an important step towards different types of cardiovascular disease. The role of oxidized low-density lipoprotein (oxLDL) in the initiation and progression of atherosclerosis has been thoroughly investigated in recent years. Moreover, clinical trials have established that diabetic patients are at a greater risk of developing atherosclerotic plaques. Hence, we aimed to review the clinical and experimental impacts of various classes of antidiabetic drugs on the circulating levels of oxLDL. Metformin, pioglitazone, and dipeptidyl peptidase-4 inhibitors were clinically associated with a suppressive effect on oxLDL in patients with impaired glucose tolerance. However, there is an insufficient number of studies that have clinically evaluated the relationship between oxLDL and newer agents such as agonists of glucagon-like peptide 1 receptor or inhibitors of sodium-glucose transport protein 2. Next, we attempted to explore the multitude of mechanisms that antidiabetic agents exert to counter the undesirable effects of oxLDL in macrophages, endothelial cells, and vascular smooth muscle cells. In general, antidiabetic drugs decrease the uptake of oxLDL by vascular cells and reduce subsequent inflammatory signaling, which prevents macrophage adhesion and infiltration. Moreover, these agents suppress the oxLDL-induced transformation of macrophages into foam cells by either inhibiting oxLDL entrance, or by facilitating its efflux. Thus, the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of antidiabetic agents abrogate changes induced by oxLDL, which can be extremely beneficial in controlling atherosclerosis in diabetic patients. Graphical Abstract: ga1