Angiotensin II Is Involved in MLKL Activation During the Development of Heart Failure Following Myocardial Infarction in Rats.

Several reports assume that myocardial necroptotic cell death is induced during the development of chronic heart failure. Although it is well accepted that angiotensin II induces apoptotic cell death of cardiac myocytes, the involvement of angiotensin II in the induction of myocardial necroptosis during the development of heart failure is still unknown. Therefore, we examined the role of angiotensin II in myocardial necroptosis using rat failing hearts following myocardial infarction and cultured cardiomyocytes.

Simvastatin Attenuates Cardiac Fibrosis under Pathophysiological Conditions of Heart Failure with Preserved Left Ventricular Ejection Fraction by Inhibiting TGF-β Signaling.

Introduction: There is still no effective treatment for heart failure with preserved left ventricular ejection fraction (HFpEF), and therapies to improve prognosis are urgently needed. Clinical studies in patients with HFpEF have shown that statins and HMG-CoA reductase inhibitors may reduce their mortality rate. However, the mechanisms underlying the effects of statins on HFpEF remain unknown.

Involvement of Hsp90 in NLRP3 inflammasome activation in the failing heart following myocardial infarction in rats.

The NLR family pyrin domain containing 3 (NLRP3) inflammasome matures interleukin (IL)-1β and induces inflammation. The molecular chaperone heat shock protein 90 (Hsp90) is known to regulate the formation of the NLRP3 inflammasome. However, the pathophysiological role of Hsp90 in the activation of the NLRP3 inflammasome in the failing heart is unclear.

Simvastatin attenuates the c-Raf/Erk and calcineurin-NFATc2 pathways via inhibition of Hsp90 activity during the development of heart failure.

Hsp90 is a molecular chaperone that contributes to the activation and stabilization of client proteins. In our previous studies, we found that inhibition of Hsp90 delayed cardiac remodeling during the development of chronic heart failure in animal models. Simvastatin, an inhibitor of HMG-CoA reductase, has been shown to inhibit Hsp90.