Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
FASEB J. 2018 Jul;32(7):3717-3729. doi: 10.1096/fj.201701173RR. Epub 2018 Feb 13.
Resolvins are innate, immune responsive, bioactive mediators generated after myocardial infarction (MI) to resolve inflammation. The MI-induced bidirectional interaction between progressive left ventricle (LV) remodeling and kidney dysfunction is known to advance cardiorenal syndrome (CRS). Whether resolvins limit MI-induced cardiorenal inflammation is unclear. Thus, to define the role of exogenous resolvin D (RvD)-1 in post-MI CRS, we subjected 8- to 12-wk-old male C57BL/6 mice to coronary artery ligation. RvD1 was injected 3 h after MI. MI mice with no treatment served as MI controls (d 1 and 5). Mice with no surgery served as naive controls. In the injected mice, RvD1 promoted neutrophil (CD11b/Ly6G) egress from the infarcted LV, compared with the MI control group at d 5, indicative of neutrophil clearance and thereby resolved inflammation. Further, RvD1-injected mice showed higher reparative macrophages (F4/80/Ly6C/CD206) in the infarcted LV than did MI control mice at d 5 after MI. RvD1 suppressed the miRNA storm at d 1 and limited the MI-induced edematous milieu in a remote area of the LV compared with the MI control at d 5 after MI. Also, RvD1 preserved the nephrin expression that was diffuse in the glomerular membrane at d 5 and 28 in MI controls, indicating renal injury. RvD1 attenuated MI-induced renal inflammation, decreasing neutrophil gelatinase-associated lipocalin and proinflammatory cytokines and chemokines in the kidney compared with the MI control. In summary, RvD1 clears MI-induced inflammation by increasing resolving leukocytes and facilitates renoprotective mechanisms to limit CRS in acute and chronic heart failure.-Halade, G. V., Kain, V., Serhan, C. N. Immune responsive resolvin D1 programs myocardial infarction-induced cardiorenal syndrome in heart failure.
解析素是先天的、免疫反应的、生物活性介质，在心肌梗死 (MI) 后产生以解决炎症。已知 MI 引起的进行性左心室 (LV) 重塑和肾功能障碍之间的双向相互作用会导致心肾综合征 (CRS)。解析素是否限制 MI 引起的心肌肾炎症尚不清楚。因此，为了确定外源性解析素 D (RvD)-1 在 MI 后 CRS 中的作用，我们将 8-12 周龄的雄性 C57BL/6 小鼠进行冠状动脉结扎。MI 后 3 小时注射 RvD1。未治疗的 MI 小鼠作为 MI 对照组 (d1 和 d5)。未行手术的小鼠作为幼稚对照组。在注射小鼠中，与 MI 对照组相比，RvD1 促进中性粒细胞 (CD11b/Ly6G) 从梗死的 LV 中迁出，这表明中性粒细胞清除和炎症得到解决。此外，与 MI 对照组相比，RvD1 注射小鼠在 MI 后第 5 天的梗死 LV 中显示出更高的修复性巨噬细胞 (F4/80/Ly6C/CD206)。与 MI 对照组相比，RvD1 在 MI 后第 1 天抑制 miRNA 风暴，并在 LV 的远处区域限制 MI 诱导的水肿环境。此外，RvD1 在 MI 对照组弥漫在肾小球膜中的肾磷蛋白表达在 MI 后第 5 天和第 28 天得到保留，表明肾损伤。RvD1 减轻 MI 诱导的肾脏炎症，减少肾脏中的中性粒细胞明胶酶相关脂质运载蛋白和促炎细胞因子和趋化因子，与 MI 对照组相比。总之，RvD1 通过增加解决白细胞来清除 MI 诱导的炎症，并促进肾保护机制以限制急性和慢性心力衰竭中的 CRS。
