Statins work lipid-lowering medicines with a good safety profile that have become, over the years, the first-line therapy for patients with dyslipidemia and a real cornerstone of cardiovascular (CV) preventive therapy
November 28, 2020
Statins work lipid-lowering medicines with a good safety profile that have become, over the years, the first-line therapy for patients with dyslipidemia and a real cornerstone of cardiovascular (CV) preventive therapy. even report IL-1 secretion to rise after treatment with statins, with a potential impact on the inflammatory microenvironment and glycemic control. Here, we will summarize evidence of the role of statins in the prevention and treatment of myocardial infarction and diabetic cardiomyopathy. In accordance with the dual lipid-lowering and anti-inflammatory effect of these drugs and in light of the important results achieved by IL-1 inhibition through canakinumab in CV secondary prevention, we will dissect the current evidence linking statins with IL-1 and outline the possible benefits of a potential double treatment with statins and canakinumab. and proven to inhibit the production of cholesterol molecules . Further experiments showed that statins occupy a portion of the rate-controlling enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGR) by binding its active site with very high affinity, thus displacing the natural substrate, HMG-CoA, and inhibiting its function . Furthermore, the statin-related reduction of circulatory lipoprotein induces the hepatic expression of low-density lipoprotein (LDL) receptor (LDLR) and LDL clearance from the bloodstream, thus accounting for a further decrease in circulating cholesterol levels . Thanks to this dual mechanism of action and a good safety profile, both natural and synthetic statins became, over the years, the first-line therapy for dyslipidemia patients and a real cornerstone of cardiovascular (CV) preventive therapy. Soon after first trials with statins were published, evidence suggested that those compounds might have putative, non-lipid-related effects. Both Cholesterol and Recurrent Events (CARE) and Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trials showed that their overall cardiovascular benefit was disproportionate towards the magnitude of lipid decrease [4,5]. Furthermore, the speed where statins exercised their protecting role was quicker than that acquired with additional lipid-lowering interventions such Cspg2 as for example ileal bypass . These EVP-6124 hydrochloride pleiotropic results have been linked to statins inhibitory influence on the activation of different intracellular signaling mediators downstream the mevalonate pathways (i.e., Rho, Ras, and Rac protein) alongside immediate stimulatory results on peroxisome proliferator-activated (PPAR)- and – . Swelling and Lipids are carefully interconnected and donate to the pathogenesis of all CV disease [8,9]. Among those, myocardial infarction continuously prices being among the most essential factors behind mortality and morbidity world-wide, while diabetic cardiomyopathy can be an growing disease whose occurrence is set to increase within the next years following a increased prevalence from the diabetic human population. Even though the part of circulating lipoproteins in the dedication of the average person CV risk have already been appreciated since in the past, recently, experimental and medical observations support a job for systemic inflammation . Inflammatory cytokines and cells have already been determined in human being atherosclerotic vessels, and their powerful regulation plays a significant part in cardiac redesigning [11,12]. Observational research reported a lower life expectancy CV risk in individuals becoming treated with anti-inflammatory EVP-6124 hydrochloride real estate agents for immunological disease (e.g., rheumatoid arthritis), supporting the concept of inflammation as a valuable target for CV EVP-6124 hydrochloride prevention . However, not all anti-inflammatory drugs provided efficacy in reducing CV risk as different trials designed to test this hypothesis gave negative results (i.e., Cardiovascular Inflammation Reduction Trial [CIRT] testing methotrexate), and non-steroidal anti-inflammatory agents are even associated with an increased CV morbidity [14,15]. Of importance, in 2017, the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) trial showed the efficacy of IL-1 neutralization in patients with established coronary heart disease, highlighting this cytokine and its pathway as effective targets, as well as suggesting that specific interaction with inflammatory mediators might be a better strategy than providing anti-inflammation in a global fashion [16,17]. In this review article, we aim to summarize evidence of the role of statin treatment in myocardial infarction and prevention of myocardial remodeling in patients with diabetes mellitus..