HMGCoA reductase inhibition reverses myocardial fibrosis and diastolic dysfunction through AMP-activated protein kinase activation in a mouse model of metabolic syndrome

Abstract

In this model of MS, statin treatment reverses myocardial remodelling and improves ventricular relaxation through AMPK-mediated anti-fibrotic effects.

CTRP3 attenuates post-infarct cardiac fibrosis by targeting Smad3 activation and inhibiting myofibroblast differentiation

“…Considerable pieces of evidence indicate that AMPK responds to different stimuli and suppresses cardiac fibrosis [43][44][45][46]. Metformin-activated AMPK suppresses the phosphorylation and nuclear translocation of Smad3 in response to TGF-β1 and inhibits cardiac fibrosis and collagen synthesis in CFs [46].…”

Molecular and cellular mechanisms of glucagon-like peptide-1 receptor agonist-mediated attenuation of cardiac fibrosis

“…While largescale clinical studies, possibly subject to uncontrolled variables, have yet to confirm the potentially beneficial cardiovascular effects of these agents, 44 pre-clinical studies continue to suggest a cardioprotective/anti-fibrotic role for this class of agents, potentially mediated via glucose lowering, 45 influences on hormones regulating glucose homeostasis 46 and direct effects on the myocardium.…”

Alteration of splice site selection in the LMNA gene and inhibition of progerin production via AMPK activation

“…Of particular interest is the observation by Columbaro et al that the combined use of trichostatin A and mevinolin (lovastatin), a member of the statin class of cholesterol-lowering medications that inhibits HMG-CoA reductase and farnesyltransferase, leads to a significant reduction of progerin levels in cultured HGPS fibroblasts, leading to a rescue of nuclear-shape abnormalities, heterochromatin organization, and a recovery of ribonucleoprotein staining patterns [121]. Similar to trichostatin A and other HDAC inhibitors, mevinolin/lovastatin as well as other members of the statin family (simvastatin, atorvastatin, pitavastatin, fluvastatin, pravastatin, and rosuvastatin) have all been shown to activate AMPK [122][123][124][125][126][127].…”