Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H352-H363. doi: 10.1152/ajpheart.00328.2020. Epub 2020 Oct 30.
Alamandine is the newest identified peptide of the renin-angiotensin system (RAS) and has protective effects in the cardiovascular system. Although the involvement of classical RAS components in the genesis and progression of cardiac remodeling is well known, less is known about the effects of alamandine. Therefore, in the present study we investigated the effects of alamandine on cardiac remodeling induced by transverse aortic constriction (TAC) in mice. Male mice (C57BL/6), 10-12 wk of age, were divided into three groups: sham operated, TAC, and TAC + ALA (30 µg/kg/day alamandine for 14 days). The TAC surgery was performed under ketamine and xylazine anesthesia. At the end of treatment, the animals were submitted to echocardiographic examination and subsequently euthanized for tissue collection. TAC induced myocyte hypertrophy, collagen deposition, and the expression of matrix metalloproteinase (MMP)-2 and transforming growth factor (TGF)-β in the left ventricle. These markers of cardiac remodeling were reduced by oral treatment with alamandine. Western blotting analysis showed that alamandine prevents the increase in ERK1/2 phosphorylation and reverts the decrease in 5'-adenosine monophosphate-activated protein kinase (AMPK)α phosphorylation induced by TAC. Although both TAC and TAC + ALA increased SERCA2 expression, the phosphorylation of phospholamban in the Thr17 residue was increased solely in the alamandine-treated group. The echocardiographic data showed that there are no functional or morphological alterations after 2 wk of TAC. Alamandine treatment prevents myocyte hypertrophy and cardiac fibrosis induced by TAC. Our results reinforce the cardioprotective role of alamandine and highlight its therapeutic potential for treating heart diseases related to pressure overload conditions. Alamandine is the newest identified component of the renin-angiotensin system protective arm. Considering the beneficial effects already described so far, alamandine is a promising target for cardiovascular disease treatment. We demonstrated for the first time that alamandine improves many aspects of cardiac remodeling induced by pressure overload, including cell hypertrophy, fibrosis, and oxidative stress markers.
阿马林丁是肾素-血管紧张素系统（RAS）中最新鉴定的肽，在心血管系统中具有保护作用。尽管经典 RAS 成分在心脏重构的发生和进展中的作用已被充分认识，但对阿马林丁的作用知之甚少。因此，在本研究中，我们研究了阿马林丁对小鼠主动脉缩窄（TAC）诱导的心脏重构的影响。雄性小鼠（C57BL/6），10-12 周龄，分为三组：假手术组、TAC 组和 TAC+ALA 组（TAC 术后每天给予 30μg/kg 阿马林丁，共 14 天）。TAC 手术在氯胺酮和甲苯噻嗪麻醉下进行。治疗结束时，对动物进行超声心动图检查，随后处死采集组织。TAC 诱导心肌细胞肥大、胶原沉积以及左心室基质金属蛋白酶（MMP）-2 和转化生长因子（TGF）-β的表达。口服阿马林丁可减轻这些心脏重构标志物。Western 印迹分析显示，阿马林丁可防止 ERK1/2 磷酸化增加，并逆转 TAC 诱导的 5'-腺苷一磷酸激活蛋白激酶（AMPK）α磷酸化减少。虽然 TAC 和 TAC+ALA 均增加 SERCA2 的表达，但仅在阿马林丁处理组中，磷酸化酶 17 位苏氨酸的磷蛋白（phospholamban）增加。超声心动图数据显示，TAC 后 2 周无功能或形态改变。阿马林丁治疗可预防 TAC 诱导的心肌细胞肥大和心肌纤维化。我们的结果强化了阿马林丁的心脏保护作用，并强调了其在治疗与压力超负荷相关的心脏疾病方面的治疗潜力。阿马林丁是肾素-血管紧张素系统保护臂中最新鉴定的成分。考虑到迄今为止已描述的有益作用，阿马林丁是心血管疾病治疗的有希望的靶点。我们首次证明，阿马林丁可改善压力超负荷诱导的心脏重构的许多方面，包括细胞肥大、纤维化和氧化应激标志物。
