Anti-inflammatory Effect of B-Type Natriuretic Peptide Postconditioning During Myocardial Ischemia–Reperfusion: Involvement of PI3K/Akt Signaling Pathway

Abstract

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia-reperfusion (I/R) injury. B-type natriuretic peptide (BNP) postconditioning has been reported to reduce myocardial I/R injury. The present study investigated whether postconditioning of BNP could reduce myocardial I/R injury by inhibiting HMGB1 expression and the potential mechanisms in rats. The left anterior descending coronary arteries of rats were occluded to induce ischemia for 30 min and reopened to imitate reperfusion for 4 h. The rats were treated with BNP (0.03 μg/kg min, i.v.) 15 min before reperfusion until the end of the procedure, with or without treatment of LY294002 (an inhibitor of phosphoinositide 3-kinase (PI3K), 0.3 mg/kg, i.v.), which was injected 20 min before reperfusion. Lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and infarct size were measured. Phospho-Akt, total Akt, and HMGB1 expression were assessed by immunoblotting. The results showed that treatment of BNP postconditioning could significantly decrease the infarct size and the levels of LDH and CK after 4-h reperfusion (all p<0.05). BNP postconditioning could also significantly inhibit the increases of TNF-α and IL-6 (both p<0.05). In addition, BNP postconditioning could significantly inhibit HMGB1 expression induced by I/R (p<0.05). Administration of LY294002 abolished the effects of BNP postconditioning on myocardial I/R injury and the expressions of phospho-Akt and HMGB1 (all p<0.05). The present study suggests that postconditioning of BNP could protect against myocardial I/R injury which may be associated with inhibiting HMGB1 expression, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of BNP postconditioning.

Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice

“…In the later stages of IRI, the role of macrophages transforms into an anti-inflammatory one, as they repair renal damage (Duffield, 2011;Huen and Cantley, 2015). It has been previously shown that BNP can inhibit cardiac inflammation induced by IRI (Hu et al, 2014). We also observed macrophage infiltration at an early stage of IRI (24 h after reperfusion) and noticed a pro-inflammatory phenotype of the macrophages (Kinsey, 2014;Huen and Cantley, 2015).…”

“…BNP belongs to the natriuretic peptide family and is synthesized and secreted mainly by cardiac myocytes, where it is used as a hemodynamic parameter that can reflect left ventricular dysfunction and decompensated heart failure (Jaffe et al, 2006). Many studies have demonstrated that BNP functions as an anti-inflammatory, antioxidant and anti-apoptotic factor that can protect the heart from IRI (Hu et al, 2014). However, whether BNP can also protect the kidney from damage is unclear.…”

Protective effect of glycyrrhizin on myocardial ischemia/reperfusion injury-induced oxidative stress, inducible nitric oxide synthase and inflammatory reactions through high-mobility group box 1 and mitogen-activated protein kinase expression

“…For patients with acute or chronic coronary artery diseases, both IFN-γ and TNF-α are significantly increased. Intervention of TNF-α may improve myocardial ischemia, with the time of intervention being either before reperfusion or at the beginning of reperfusion (31). Intervention at the beginning of reperfusion was discovered to have an influential role in the recovery of myocardium (31).…”

“…Intervention of TNF-α may improve myocardial ischemia, with the time of intervention being either before reperfusion or at the beginning of reperfusion (31). Intervention at the beginning of reperfusion was discovered to have an influential role in the recovery of myocardium (31). It is therefore feasible to consider the inflammatory factor TNF-α, as a useful treatment at the beginning of reperfusion (29).…”

The multifaceted role of natriuretic peptides in metabolic syndrome

“…There are many reports that have been published regarding anti-inflammatory and anticancer activity of natriuretic peptides [114–116]. The NPR-A has been reported to be expressed in various types of cancer, such as lung cancer, ovarian cancer, gastric cancer and prostate cancer [117–119].…”