Alamandine alleviated heart failure and fibrosis in myocardial infarction mice

Abstract

Alamandine (Ala) is the newest identified peptide of the renin-angiotensin system and has protective effect on myocyte hypertrophy. However, it is still unclear whether Ala can alleviate heart failure (HF). The aim of this study was to explore the effects of Ala on HF and the related cardiac fibrosis, and to probe the mechanism. HF model was induced by myocardial infarction (MI) in mice. Four weeks after MI, Ala was administrated by intraperitoneal injection for two weeks. Ala injection significantly improved cardiac dysfunction of MI mice in vivo. The cardiac fibrosis and the related biomarkers were attenuated after Ala administration in HF mice in vivo. The increases of collagen I, alpha-smooth muscle actin and transforming growth factor-beta induced by oxygen–glucose deprivation (OGD) in neonatal rat cardiac fibroblasts (NRCFs) were inhibited by Ala treatment in vitro. The biomarkers of apoptosis were elevated in NRCFs induced by OGD, which were attenuated after treating with Ala in vitro. The enhancement of oxidative stress in the heart of MI mice or in the NRCFs treated with OGD was suppressed by treating with Ala in vivo and in vitro. These effects of Ala were reversed by tBHP, an exogenous inducer of oxidative stress in vitro. These results demonstrated that Ala could alleviate cardiac dysfunction and attenuate cardiac fibrosis via inhibition of oxidative stress.

Evidence that the monoamine oxidase B (MAO-B) plays a central role in the inotropic dysfunction induced by genetic deletion of the Mas-related-G protein-coupled receptor D (MrgD) in mice

“…It is worthy to highlight that the treatment of cardiomyocytes derived from the hypertensive rat TGR (mREN2)27 with alamandine promoted the opposite effects, enhancing contractility, promoting the phosphorylation of PLN on Thr-17 and a higher Ca 2+ transient and accelerated Ca 2+ reuptake 65 . In addition, the alamandine treatment of failing hearts due to myocardial infarction reduced oxidative stress and reverted the cardiac damage caused by ischemia/reperfusion, increasing ejection fraction and fractional shortening 66 .…”

Progress in the treatment of diabetic cardiomyopathy, a systematic review

“…116 A study finds that Alamandine, the newest identified peptide of the renin-angiotensin system, attenuates myocardial oxidative stress and inflammatory responses and prevents myocardial lesions in a DM mouse model. 117 Captopril, an ACEI inhibitor, improved end-diastolic pressure elevation and inhibited myocardial fibrosis in spontaneous DM rats after treatment for 4 months, thus playing a preventive role in DCM. 118 Although ACEIs are generally well-tolerated and have no significant immediate side effects, some studies suggest that reducing Ang II production may lead to adverse effects such as hypotension, acute renal failure, and hyperkalemia.…”

“…Experimental studies suggest that RAAS inhibitors may prevent DCM by inhibiting cardiac‐specific NF‐κB signaling 116 . A study finds that Alamandine, the newest identified peptide of the renin‐angiotensin system, attenuates myocardial oxidative stress and inflammatory responses and prevents myocardial lesions in a DM mouse model 117 . Captopril, an ACEI inhibitor, improved end‐diastolic pressure elevation and inhibited myocardial fibrosis in spontaneous DM rats after treatment for 4 months, thus playing a preventive role in DCM 118 …”

Counter-regulatory RAS peptides: new therapy targets for inflammation and fibrotic diseases?

“…In a rat model of cardiac ischemia-reperfusion injury, the administration of this peptide reduced the presence of fibrotic markers, increasing the phosphorylation levels of ERK and JNK, while NF-κB decreased ( Song et al, 2019 ). Another mechanism associated with the effects of alamandine was observed in liver and lung, where the peptide attenuated the presence of fibrosis by attenuating autophagy activated by ROS-dependent reactive oxygen species ( Huang et al, 2020 ; Gong et al, 2022 ; Zhao et al, 2022 ). ( Figure 3 ).…”