Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.
Drug Des Devel Ther. 2023 Oct 11;17:3073-3083. doi: 10.2147/DDDT.S421894. eCollection 2023.
Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear.
Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis.
17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68 macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue.
17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.
炎症反应增加导致压力超负荷引起的心肌重构。17(R)-Resolvin D1（17(R)-RvD1）是一种源自二十二碳六烯酸的强效脂质介质，具有抗炎和促解决特性。然而，17(R)-RvD1与压力超负荷引起的心肌肥厚之间的关联尚不清楚。
进行横主动脉缩窄（TAC）手术建立心肌肥厚模型。C57BL/6J 小鼠随机分为 Sham、TAC 和 TAC+17(R)-RvD1 组。在 TAC 手术前注射 17(R)-RvD1（2μg/kg，腹腔注射），手术后每隔一天注射一次，共 4 周。Sham 组和 TAC 组的小鼠均注射等量生理盐水。然后评估心功能并收集心脏组织进行生物学分析。
17(R)-RvD1 治疗减轻了 TAC 引起的左心室直径增加和左心室收缩力下降，减轻了心肌细胞横截面积增加，并下调了肥厚基因的表达。此外，17(R)-RvD1 减轻了心肌纤维化，表现为 LV 胶原体积减少和纤维化基因表达降低。此外，17(R)-RvD1 改善了心脏组织中的炎症反应，表现为 CD68 巨噬细胞浸润减少和促炎细胞因子（包括 TNF-α、IL-1β 和 IL-6）产生减少。17(R)-RvD1 治疗显著抑制了 TAC 手术后 NLRP3 炎性小体的激活，这可能是心脏组织炎症减轻的原因。
17(R)-RvD1 减轻了压力超负荷引起的心肌肥厚和纤维化，其可能的机制与抑制 NLRP3 炎性小体有关。17(R)-RvD1 可作为治疗心肌肥厚的潜在药物。
