Metabolic Syndrome and Chronic Simvastatin Therapy Enhanced Human Cardiomyocyte Stress before and after Ischemia- Reperfusion in Cardio-Pulmonary Bypass Patients

Abstract

The first two authors contributed equally to the work Metabolic syndrome (MetS) is a set of metabolic alterations including high levels of low-density lipoprotein (LDL), which increase the risk of cardiomyopathy often leading to surgery. Despite inducing myopathy, statins are widely used to lower LDL. Cardiopulmonary bypass (Cpb) causes oxidative stress and metabolic injury, altering mitochondrial expression (Grp75) and endoplasmic reticulum (Grp78) chaperones, apoptotic enzymes (Bcl2 family) and increasing cardiomyocyte lipidllipofuscin storage. We believe that cardiomyocytes from patients with MetS may be more sensitive to surgical stress, in particular after simvastatin therapy (MetS+Stat). The study group included ten patients with MetS, ten patients with Mets+Stat and ten healthy subjects. Myocardial biopsies were obtained both before and after-Cpb. Grp75, Grp78, Bax, Bcll, lipids, lipofuscin and fibrosis were evaluated by immunol histochemistry. MetS cardiomyocytes had higher Grp75, Bax, fibrosis and lipofuscin. MetS+Stat had lower Grp75 and higher Grp78 expressions, high Bax, fewer fibrosis and higher lipofuscin content. Cpb did not vary the fibrosis and lipidsllipofuscin content, although it influenced the chaperones and Bax expression in all groups. These changes were more profound in patients with MetS and even more so in patients with MetS+Stat. The results suggest that MetS and MetS+Stat cardiomyocytes were more highly stressed after-Cpb, Interestingly, simvastatin caused high stress even before-Cpb.Metabolic syndrome (MetS) is a cluster ofvarious clinical features. This syndrome increases the risk of metabolic cardiomyopathy and coronary artery disease (CAD). CAD can cause myocardial ischemia requiring surgical myocardial revascularization (1) and causes intrinsic metabolic and structural cardiomyocyte damage. Many drugs are currently used to treat MetS, both to reduce risk factors and to

Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney

“…Extensive evidence supports the efficacy of dietary supplementation with a balanced amino acid mixture enriched in essential amino acids (EAAm) in clinical disorders characterized by deficits of energy production, including ageing, type 2 diabetes, heart failure, alcohol consumption, and renal failure (Cano et al 2006; Valerio et al 2011; Corsetti et al 2012). It is widely accepted that the kidneys play a major role in amino acid metabolism and, partially, in the regulation of amino acid plasma levels.…”

Cardiomyocyte changes in the metabolic syndrome and implications for endogeneous protective strategies

“…Prolonged endoplasmatic reticulum stress may contribute to cardiac myocyte apoptosis during the progression from cardiac hypertrophy to failure [124]. However, chronic statin intake might be hazardous in ischemiareperfusion injury as suggested by Corsetti et al in cardiopulmonary bypass patients [64].…”

“…For example, metabolic syndrome and chronic simvastatin therapy may lead to enhanced human cardiomyocyte stress before and after ischemia reperfusion [64], having important implications for several interventional procedures.…”