The Role of Natriuretic Peptides in the Regulation of Cardiac Tolerance to Ischemia/Reperfusion and Postinfarction Heart Remodeling

In the past 10 years, mortality from acute myocardial infarction has not decreased despite the widespread introduction of percutaneous coronary intervention. The reason for this situation is the absence in clinical practice of drugs capable of preventing reperfusion injury of the heart with high efficiency. In this regard, noteworthy natriuretic peptides (NPs) which have the infarct-limiting effect, prevent reperfusion cardiac injury, prevent adverse post-infarction remodeling of the heart. Atrial natriuretic peptide does not have the infarct-reducing effect in rats with alloxan-induced diabetes mellitus. NPs have the anti-apoptotic and anti-inflammatory effects. There is indirect evidence that NPs inhibit pyroptosis and autophagy. Published data indicate that NPs inhibit reactive oxygen species production in cardiomyocytes, aorta, heart, kidney and the endothelial cells. NPs can suppress aldosterone, angiotensin II, endothelin-1 synthesize and secretion. NPs inhibit the effects aldosterone, angiotensin II on the post-receptor level through intracellular signaling events. NPs activate guanylyl cyclase, protein kinase G and protein kinase A, and reduce phosphodiesterase 3 activity. NO-synthase and soluble guanylyl cyclase are involved in the cardioprotective effect of NPs. The cardioprotective effect of natriuretic peptides is mediated via activation of kinases (AMPK, PKC, PI3 K, ERK1/2, p70s6 k, Akt) and inhibition of glycogen synthase kinase 3 beta. The cardioprotective effect of NPs is mediated via sarcolemmal K(ATP)channel and mitochondrial K(ATP)channel opening. The cardioprotective effect of brain natriuretic peptide is mediated via MPT pore closing. The anti-fibrotic effect of NPs may be mediated through inhibition TGF-beta 1 expression. Natriuretic peptides can inhibit NF-kappa B activity and activate GATA. Hemeoxygenase-1 and peroxisome proliferator-activated receptor gamma may be involved in the infarct-reducing effect of NPs. NPs exhibit the infarct-limiting effect in patients with acute myocardial infarction. NPs prevent post-infarction remodeling of the heart. To finally resolve the question of the feasibility of using NPs in AMI, a multicenter, randomized, blind, placebo-controlled study is needed to assess the effect of NPs on the mortality of patients after AMI.

Automated summary

Natriuretic peptides have various cardioprotective effects such as preventing reperfusion injury, limiting infarction, anti-apoptotic and anti-inflammatory effects. They regulate multiple signaling pathways, reduce mortality in heart disease patients, but have limited effectiveness in diabetic rats.