Fatty acid-binding protein 5 (FABP5) is an important member of the FABP family and plays a vital role in the metabolism of fatty acids. However, few studies have examined the role of FABP5 in pathological cardiac remodeling and heart failure. The aim of this study was to explore the role of FABP5 in transverse aortic constriction (TAC)-induced pathological cardiac remodeling and dysfunction in mice. Quantitative RT-PCR (qRT-PCR) and western blotting (WB) analysis showed that the levels of FABP5 mRNA and protein, respectively, were upregulated in hearts of the TAC model. Ten weeks after TAC in FABP5 knockout and wild type control mice, echocardiography, histopathology, qRT-PCR, and WB demonstrated that FABP5 deficiency aggravated cardiac injury (both cardiac hypertrophy and fibrosis) and dysfunction. In addition, transmission electron microscopy, ATP detection, and WB revealed that TAC caused severe impairment to mitochondria in the hearts of FABP5-deficient mice compared with that in control mice. When FABP5 was downregulated by siRNA in primary mouse cardiac fibroblasts, FABP5 silencing increased oxidative stress, reduced mitochondrial respiration, and increased the expression of myofibroblast activation marker genes in response to treatment with transforming growth factor-β. Our findings demonstrate that FABP5 deficiency aggravates cardiac pathological remodeling and dysfunction by damaging cardiac mitochondrial function.

脂肪酸结合蛋白5（FABP5）是FABP家族的重要成员，在脂肪酸代谢中发挥着至关重要的作用。然而，很少有研究探讨 FABP5 在病理性心脏重塑和心力衰竭中的作用。本研究的目的是探讨 FABP5 在横主动脉缩窄 (TAC) 诱导的小鼠病理性心脏重塑和功能障碍中的作用。定量 RT-PCR (qRT-PCR) 和蛋白质印迹 (WB) 分析表明，TAC 模型心脏中 FABP5 mRNA 和蛋白质水平分别上调。对 FABP5 敲除小鼠和野生型对照小鼠进行 TAC 十周后，超声心动图、组织病理学、qRT-PCR 和 WB 证明 FABP5 缺乏会加重心脏损伤（心脏肥大和纤维化）和功能障碍。此外，透射电子显微镜、ATP 检测和 WB 表明，与对照小鼠相比，TAC 对 FABP5 缺陷小鼠心脏中的线粒体造成严重损害。当 FABP5 在原代小鼠心脏成纤维细胞中被 siRNA 下调时，FABP5 沉默会增加氧化应激，减少线粒体呼吸，并增加肌成纤维细胞活化标记基因的表达，以响应转化生长因子-β 的治疗。我们的研究结果表明，FABP5 缺乏会损害心脏线粒体功能，从而加剧心脏病理重塑和功能障碍。