stilbenes and Myocarditis

A complex set of metabolic and inflammatory processes are involved in the development of cardiac hypertrophy. Accumulating evidence indicates an important role for Sirt1 in cardiac function, whereas peroxisome proliferator-activated receptor-α (PPARα) is a master controller of cardiac lipid metabolism and plays a protective role on cardiac hypertrophy. The objective of the present study was to explore the relationships between Sirt1 and PPARα in the control of hypertrophy, metabolism, and inflammation processes in the heart.. Neonatal cardiomyocytes (NCMs) were used for studies in vitro. Both the activation of Sirt1 with resveratrol (RSV) and overexpression of Sirt1 inhibited phenylephrine (PE)-induced NCM hypertrophy and prevented PE-induced down-regulation of fatty acid oxidation genes. Sirt1 also inhibited the PE-induced increase in mRNA levels of the pro-inflammatory cytokine monocyte chemoattractant protein-1 in NCMs and blocked the enhanced nuclear factor-κB (NF-κB) activity associated with exposure to PE. Importantly, inhibition of PPARα suppressed the beneficial effects of Sirt1 on hypertrophy, fatty acid metabolism, and inflammation. Co-immunoprecipitation studies revealed that overexpression of Sirt1 enhanced PPARα binding to the p65 subunit of NF-κB and led to p65-deacetylation in NCMs. Moreover, Sirt1 overexpression led to the deacetylation of the PPARα co-activator PGC-1α. Consistent with these observations in vitro, isoproterenol-induced cardiac hypertrophy, metabolic dysregulation, and inflammation in vivo were prevented by RSV in wild-type mice but not in PPARα-null mice.. Collectively, these findings reveal a major involvement of the Sirt1-PPARα interaction in the protective role of Sirt1 against cardiac hypertrophy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiomegaly; Cardiotonic Agents; Cells, Cultured; Energy Metabolism; Fatty Acids; Gene Expression; Lipid Metabolism; Mice; Mice, Mutant Strains; Myocarditis; Myocytes, Cardiac; NF-kappa B; Oxidation-Reduction; PPAR alpha; Rats; Rats, Sprague-Dawley; Resveratrol; Sirtuin 1; Stilbenes

Topics: Animals; Cardiomegaly; Heart; Myocarditis; Myocytes, Cardiac; Rats; Resveratrol; Stilbenes; TOR Serine-Threonine Kinases; Triiodothyronine

Some research has shown that resveratrol can ameliorate myocardial injury and improve cardiac function in mice with acute viral myocarditis (VMC), and can inhibit cardiac fibroblast proliferation and myofibroblast differentiation in vitro. This study was designed to investigate whether resveratrol has similar effects in the mouse model of chronic VMC.. One hundred mice were inoculated with 0.3 mL of Coxsackievirus B3 1*106 TCID50. Thirty days later, the survivors (n=62) were used as a model of chronic VMC, and were randomly assigned to 4 groups: untreated VMC, and low- (10 mg/kg), middle- (100 mg/kg) and high-dose (1 000 mg/kg) resveratrol-treated VMC (once daily, for 30 days). Ten mice which received neither Coxsackievirus B3 nor resveratrol treatment served as the control group. After 30 days of resveratrol treatment, the mice were sacrificed. Serum concentrations of collagenous pre-peptides (PINP, PICP and PIIINP) were assessed using ELISA. Hematoxylin-eosin staining, picrosirius red staining and circularly polarized light were used to examine the histochemistry of myocardial collagen.. The myocardial collagen volume fraction in the high-dose (0.74+/-0.19) and the middle-dose (1.07+/-0.12) resveratrol-treated VMC groups was significantly lower than that in the untreated VMC (2.33+/-0.18) and the low-dose resveratrol-treated VMC (2.17+/-0.19) groups (P<0.05). Compared with the untreated VMC group, serum concentrations of PICP and PIIINP in the high-dose and the middle-dose resveratrol-treated VMC groups were significantly reduced (P<0.05), while PINP concentrations increased significantly (P<0.05).. Resveratrol can inhibit hyperplasia of myocardial collagen in the mouse model of chronic VMC, acting as an effective anti-fibrotic agent in the myocardium.

Topics: Animals; Chronic Disease; Collagen Type I; Collagen Type II; Coxsackievirus Infections; Enterovirus B, Human; Fibrosis; Male; Mice; Mice, Inbred BALB C; Myocarditis; Myocardium; Peptide Fragments; Procollagen; Resveratrol; Stilbenes

Myosin-induced autoimmune myocarditis of rats is a model of human dilated cardiomyopathy. Resveratrol is a natural polyphenol found in grapes and wine that is reported to have cardioprotective and immunomodulatory effects.. To examine the effect of resveratrol on myocarditis, vehicle or resveratrol (50 mg/kg per day) was administered to cardiac myosin immunized rats 1 day before the immunization. At 14 days after immunization, resveratrol had preserved cardiac function of myosin-immunized rats according to echocardiographic analysis. The heart weight/tibial length ratio of vehicle-treated myosin-immunized rats was increased by 1.8-fold compared with unimmunized rats, and resveratrol attenuated the heart weight increase. Resveratrol significantly decreased cellular infiltration, fibrosis, and expression of inflammatory cytokines in the myocardium. Expressions of antioxidant genes were increased in myosin-immunized hearts, and resveratrol decreased those expressions. Resveratrol also attenuated myocarditis 21 days after immunization. SIRT1, a potential effector of resveratrol, was increased in the myocardium of myosin-immunized rats compared with unimmunized rats. The SIRT1 protein was localized mainly in infiltrating mononuclear cells.. Resveratrol significantly ameliorated myocardial injury and preserved cardiac function in a rat model of autoimmune myocarditis. Resveratrol may be a therapeutic modality for myocarditis.

Topics: Animals; Autoimmune Diseases; Cardiomegaly; Cardiomyopathy, Dilated; Cardiotonic Agents; Chemotaxis, Leukocyte; Disease Models, Animal; Electrocardiography; Female; Inflammation; Leukocytes, Mononuclear; Myocarditis; Myosins; Rats; Rats, Inbred Lew; Resveratrol; Sirtuin 1; Sirtuins; Stilbenes