Department of Cardiovascular Medicine, The First Affliated Hospital of Ningbo University, Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, China.
Department of Cardiology, Wenling First People's Hospital, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenzhou, China.
J Cell Mol Med. 2023 Sep;27(17):2562-2571. doi: 10.1111/jcmm.17854. Epub 2023 Aug 16.
Previous studies have reported that visfatin can regulate macrophage polarisation, which has been demonstrated to participate in cardiac remodelling. The aims of this study were to investigate whether visfatin participates in transverse aortic constriction (TAC)-induced cardiac remodelling by regulating macrophage polarisation. First, TAC surgery and angiotensin II (Ang II) infusion were used to establish a mouse cardiac remodelling model, visfatin expression was measured, and the results showed that TAC surgery or Ang II infusion increased visfatin expression in the serum and heart in mice, and phenylephrine or hydrogen peroxide promoted the release of visfatin from macrophages in vitro. All these effects were dose-dependently reduced by superoxide dismutase. Second, visfatin was administered to TAC mice to observe the effects of visfatin on cardiac remodelling. We found that visfatin increased the cross-sectional area of cardiomyocytes, aggravated cardiac fibrosis, exacerbated cardiac dysfunction, further regulated macrophage polarisation and aggravated oxidative stress in TAC mice. Finally, macrophages were depleted in TAC mice to investigate whether macrophages mediate the regulatory effect of visfatin on cardiac remodelling, and the results showed that the aggravating effects of visfatin on oxidative stress and cardiac remodelling were abrogated. Our study suggests that visfatin enhances cardiac remodelling by promoting macrophage polarisation and enhancing oxidative stress. Visfatin may be a potential target for the prevention and treatment of clinical cardiac remodelling.
先前的研究已经表明内脂素可以调节巨噬细胞极化，而巨噬细胞极化已被证明参与了心脏重构。本研究旨在探讨内脂素是否通过调节巨噬细胞极化参与了主动脉缩窄（TAC）诱导的心脏重构。首先，通过 TAC 手术和血管紧张素 II（Ang II）输注建立了小鼠心脏重构模型，测量了内脂素的表达，结果表明 TAC 手术或 Ang II 输注增加了小鼠血清和心脏中的内脂素表达，苯肾上腺素或过氧化氢促进了巨噬细胞体外分泌内脂素。所有这些作用均被超氧化物歧化酶呈剂量依赖性降低。其次，给 TAC 小鼠注射内脂素，观察内脂素对心脏重构的影响。我们发现内脂素增加了心肌细胞的横截面积，加重了心脏纤维化，加剧了心脏功能障碍，进一步调节了 TAC 小鼠的巨噬细胞极化并加重了氧化应激。最后，在 TAC 小鼠中耗尽巨噬细胞，以探讨巨噬细胞是否介导内脂素对心脏重构的调节作用，结果表明，内脂素对氧化应激和心脏重构的加重作用被消除。我们的研究表明，内脂素通过促进巨噬细胞极化和增强氧化应激来增强心脏重构。内脂素可能是预防和治疗临床心脏重构的潜在靶点。
