Human immunodeficiency virus (HIV) infection is a risk factor of cardiovascular diseases (CVDs). HIV-infected patients exhibit cardiac dysfunction coupled with cardiac fibrosis. However, the reason why HIV could induce cardiac fibrosis remains largely unexplored. HIV-1 trans-activator of transcription (Tat) protein is a regulatory protein, which plays a critical role in the pathogenesis of various HIV-related complications. In the present study, recombinant Tat was administered to mouse myocardium or neonatal mouse cardiac fibroblasts in different doses. Hematoxylin–eosin and Masson’s trichrome staining were performed to observe the histological changes of mice myocardial tissues. EdU staining and MTS assay were used to evaluate the proliferation and viability of neonatal mouse cardiac fibroblasts, respectively. Real-time PCR and western blot analysis were used to detect CTGF, TGF-β1, and collagen I mRNA and protein expression levels, respectively. The results showed that Tat promoted the occurrence of myocardial fibrosis in mice. Also, we found that Tat increased the proliferative ability and the viability of neonatal mouse cardiac fibroblasts. The protein and mRNA expression levels of TGF-β1 and CTGF were significantly upregulated both in Tat-treated mouse myocardium and neonatal mouse cardiac fibroblasts. However, co-administration of TGF-β inhibitor abrogated the enhanced expression of collagen I induced by Tat in neonatal mouse cardiac fibroblasts. In conclusion, Tat contributes to HIV-related cardiac fibrosis through enhanced TGF-β1-CTGF signaling cascade.

人类免疫缺陷病毒（HIV）感染是心血管疾病（CVD）的危险因素。 HIV感染者表现出心脏功能障碍并伴有心脏纤维化。然而，艾滋病毒可能诱发心脏纤维化的原因在很大程度上仍未被探索。 HIV-1转录反式激活蛋白（Tat）是一种调节蛋白，在各种HIV相关并发症的发病机制中发挥着关键作用。在本研究中，将重组Tat以不同剂量施用于小鼠心肌或新生小鼠心脏成纤维细胞。苏木精-伊红和Masson三色染色观察小鼠心肌组织的组织学变化。 EdU染色和MTS测定分别用于评估新生小鼠心脏成纤维细胞的增殖和活力。采用实时PCR和蛋白质印迹分析分别检测CTGF、TGF-β1和I型胶原mRNA和蛋白表达水平。结果表明，Tat促进小鼠心肌纤维化的发生。此外，我们发现 Tat 增加了新生小鼠心脏成纤维细胞的增殖能力和活力。在 Tat 处理的小鼠心肌和新生小鼠心脏成纤维细胞中，TGF-β1 和 CTGF 的蛋白和 mRNA 表达水平显着上调。然而，同时给予 TGF-β 抑制剂可消除 Tat 在新生小鼠心脏成纤维细胞中诱导的 I 型胶原表达增强。总之，Tat 通过增强 TGF-β1-CTGF 信号级联反应导致 HIV 相关的心脏纤维化。