Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.bbadis.2021.166241 Francisco Olivares-Silva 1 , Nicole De Gregorio 2 , Jenaro Espitia-Corredor 3 , Claudio Espinoza 4 , Raúl Vivar 5 , David Silva 2 , José Miguel Osorio 4 , Sergio Lavandero 6 , Concepción Peiró 7 , Carlos Sánchez-Ferrer 7 , Guillermo Díaz-Araya 1
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Aims
Despite the broad pharmacological arsenal to treat hypertension, chronic patients may develop irreversible cardiac remodeling and fibrosis. Angiotensin II, the main peptide responsible for the Renin-Angiotensin-Aldosterone-System, has been closely linked to cardiac remodeling, hypertrophy, fibrosis, and hypertension, and some of these effects are induced by inflammatory mediators. Resolvin-D1 (RvD1) elicits potent anti-inflammatory and pro-resolving effects in various pathological models. In this study, we aimed to examine whether RvD1 ameliorates cardiac remodeling and hypertension triggered by angiotensin II.
Methods and results
Alzet® osmotic mini-pumps filled with angiotensin II (1.5 mg/kg/day) were implanted in male C57BL/6 J mice for 7 or 14 days. RvD1 (3 μg/kg/day, i.p) was administered one day after the surgery and during the complete infusion period. Blood pressure and myocardial functional parameters were assessed by echocardiography. At the end of the experimental procedure, blood and heart tissue were harvested, and plasma and histological parameters were studied. After 7 and 14 days, RvD1 reduced the increase of neutrophil and macrophage infiltration triggered by angiotensin II, and also reduced ICAM-1 and VCAM-1 expression levels. RvD1 also reduced cytokine plasma levels (IL-1β, TNF-α, IL-6, KC, MCP-1), cardiac hypertrophy, interstitial and perivascular fibrosis, and hypertension.
Conclusions
This study unveils novel cardioprotective effects of RvD1 in angiotensin II-induced hypertension and cardiac remodeling by attenuating inflammation and provides insights into a potential clinical application.
中文翻译：
Resolvin-D1 减弱血管紧张素 II 诱导的小鼠心脏炎症与预防心脏重塑和高血压有关
宗旨
尽管治疗高血压有广泛的药理学武器库，但慢性患者可能会发生不可逆的心脏重塑和纤维化。血管紧张素 II 是负责肾素-血管紧张素-醛固酮系统的主要肽，与心脏重塑、肥大、纤维化和高血压密切相关，其中一些作用是由炎症介质诱导的。Resolvin-D1 (RvD1) 在各种病理模型中引起有效的抗炎和促消退作用。在这项研究中，我们旨在检查 RvD1 是否改善由血管紧张素 II 引发的心脏重构和高血压。
方法和结果
将充满血管紧张素 II（1.5 毫克/千克/天）的 Alzet® 渗透微型泵植入雄性 C57BL/6 J 小鼠体内 7 或 14 天。RvD1 (3 μg/kg/day, ip) 在手术后一天和整个输注期间给药。通过超声心动图评估血压和心肌功能参数。在实验过程结束时，采集血液和心脏组织，并研究血浆和组织学参数。7 天和 14 天后，RvD1 减少了血管紧张素 II 引发的中性粒细胞和巨噬细胞浸润的增加，并降低了 ICAM-1 和 VCAM-1 的表达水平。RvD1 还降低细胞因子血浆水平（IL-1β、TNF-α、IL-6、KC、MCP-1）、心脏肥大、间质和血管周围纤维化以及高血压。
结论
该研究通过减轻炎症揭示了 RvD1 在血管紧张素 II 诱导的高血压和心脏重塑中的新心脏保护作用，并提供了对潜在临床应用的见解。
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