(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Myocarditis

Myocarditis, which is commonly known as heart inflammation, is a multifaceted disease that includes at least three phases. The host's immune system is mostly active during the first viral and the second autoimmune phase, when several inflammatory pathways are activated. One of the pivotal transcription factors that regulate immune responses is the nuclear factor kappa B (NF-κB). If, on one side, the acute response to heart injury activates the production of inflammatory cytokines to protect and limit host damage, on the other side sustained and long-term inflammation is one of the leading causes of cardiac hypertrophy and chronic heart failure. An update on the current knowledge of inhibitors and treatments that limit excessive inflammation in experimental and viral autoimmune myocarditis, and therapeutic approaches to cure patients with myocarditis, are described and discussed in this review.

Topics: Adiponectin; Animals; Autoimmune Diseases; Drug Delivery Systems; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Myocarditis; NF-kappa B; Treatment Outcome; Virus Diseases

This study tested the hypothesis that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor affects T cell-mediated autoimmunity through inhibition of nuclear factor-kappaB (NFkappaB) and reduces the severity of experimental autoimmune myocarditis (EAM).. EAM was induced in Lewis rats by immunization with myosin. High-dose or low-dose fluvastatin or vehicle was administered orally for 3 weeks to rats with EAM.. Fluvastatin reduced the pathophysiological severity of myocarditis. Fluvastatin inhibited expression of NFkappaB in the nuclei of myocardium in EAM. Fluvastatin reduced production of Th1-type cytokines, including interferon (IFN)-gamma and interleukin (IL)-2, and inhibited expression of inflammatory cytokine mRNAs in the myocardium. Infiltration of CD4-positive T cells into the myocardium and T cell proliferative responses were suppressed by fluvastatin. Plasma lipid levels did not differ between the groups.. Fluvastatin ameliorates EAM by inhibiting T cell responses and suppressing Th1-type and inflammatory cytokines via inactivation of nuclear factor-kappaB, and this activity is independent of cholesterol reduction.

Topics: Animals; Autoimmune Diseases; Blotting, Western; Cell Nucleus; Cell Proliferation; Fatty Acids, Monounsaturated; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Interferon-gamma; Interleukin-2; Lymphocyte Activation; Models, Animal; Myocarditis; Myocardium; Myosins; NF-kappa B; Rats; Rats, Inbred Lew; T-Lymphocytes