Department of Cardiology, First Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China.
Department of General Surgery, First Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China.
Mol Med Rep. 2019 Jan;19(1):651-659. doi: 10.3892/mmr.2018.9693. Epub 2018 Nov 26.
The present study investigated the potential role of UbiA prenyltransferase domain-containing 1 (UBIAD1) in the pathogenesis of hypertensive cardiac hypertrophy. Spontaneously hypertensive rats (SHRs) and Wistar‑Kyoto (WKY) rats at 8, 16 and 28 weeks of age were used. Blood pressure was measured using a non‑invasive tail cut‑off system. Cardiac functional index was assessed by arterial catheterization. Myocardial structure and cell apoptosis were evaluated by hematoxylin and eosin staining, and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assays, respectively. Myocardial expression of UBIAD1, coenzyme Q10 (CoQ10), endothelial nitric oxide synthase (eNOS) and atrial natriuretic peptide were evaluated by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. Circulating and myocardial expression of nitric oxide (NO) were measured using the Griess method. SHRs exhibited increased blood pressure and cardiomyocyte apoptosis, as well as cardiac hypertrophy, compared with age‑matched WKY rats. Myocardial expression of UBIAD1 was significantly decreased in SHRs in an age‑dependent manner. Similarly, myocardial CoQ10 and eNOS expression were significantly reduced in SHR compared to age‑matched WKY rats, and these expression levels additionally decreased further with aging. Serum and myocardial NO expression was additionally decreased in SHRs. Decreased UBIAD1 expression in SHR hearts was associated with decreased levels of CoQ10, eNOS and NO. Given the well‑established role of UBIAD1 in the regulation of NO signaling, reduced expression of UBIAD1 in SHR hearts potentially contributed to the pathogenesis of hypertensive cardiac hypertrophy. Therefore, UBIAD1 may represent a potential therapeutic target for clinical treatment of hypertensive cardiac hypertrophy.
本研究探讨了泛醌 A prenyltransferase 结构域包含蛋白 1（UBIAD1）在高血压性心肌肥厚发病机制中的潜在作用。使用 8、16 和 28 周龄的自发性高血压大鼠（SHR）和 Wistar-Kyoto（WKY）大鼠。采用非侵入性尾切断系统测量血压。通过动脉导管插入术评估心功能指数。通过苏木精和伊红染色和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法分别评估心肌结构和细胞凋亡。通过免疫组织化学、蛋白质印迹和逆转录定量聚合酶链反应评估心肌 UBIAD1、辅酶 Q10（CoQ10）、内皮型一氧化氮合酶（eNOS）和心钠肽的表达。使用格里斯法测量循环和心肌中一氧化氮（NO）的表达。与年龄匹配的 WKY 大鼠相比，SHR 表现出血压升高和心肌细胞凋亡以及心脏肥厚。UBIAD1 的心肌表达在 SHR 中呈年龄依赖性显著降低。同样，与年龄匹配的 WKY 大鼠相比，SHR 的心肌 CoQ10 和 eNOS 表达明显降低，并且随着年龄的增长，这些表达水平进一步降低。SHR 中的血清和心肌 NO 表达也降低。SHR 心脏中 UBIAD1 表达的降低与 CoQ10、eNOS 和 NO 水平的降低有关。鉴于 UBIAD1 在调节 NO 信号中的作用已得到充分证实，SHR 心脏中 UBIAD1 表达的降低可能导致高血压性心肌肥厚的发病机制。因此，UBIAD1 可能成为高血压性心肌肥厚临床治疗的潜在治疗靶点。
