9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice.
9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice.
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9-PAHSA 通过促进自噬通量和减少 Db/Db 小鼠心肌肥厚来改善心血管并发症
DOI：
10.3389/fphar.2021.754387
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发表时间：
2021
影响因子：
5.6
通讯作者：
Guo JC
中科院分区：
文献类型：
--
作者：
Wang YM;Mi SL;Jin H;Guo QL;Yu ZY;Wang JT;Zhang XM;Zhang Q;Wang NN;Huang YY;Zhou HG;Guo JC
动脉粥样硬化性心血管疾病是糖尿病常见的严重并发症。糖尿病性心血管疾病（DCVD）的有效和安全的治疗策略是一个巨大的需求。9-PAHSA是一种新的内源性脂肪酸，据报道可降低血糖水平和减轻炎症。本研究旨在评价9-PAHSA对DCVD的影响，并探讨其可能的作用机制。首先，采用HPLC-MS/MS法检测人血清9-PAHSA水平。然后合成并纯化9-PAHSA。将合成的9-PAHSA以50 mg/kg灌胃给db/db小鼠4周。超声评价颈动脉斑块和心脏结构。采用免疫印迹、电镜和iTRAQ检测心肌自噬。结果表明，2型糖尿病（T2 DM）患者血清9-PAHSA水平明显低于非糖尿病患者。给药9-PAHSA 2周可降低血糖水平。超声观察到9-PAHSA连续给药4周可改善db/db小鼠颈动脉血管钙化，减轻心肌肥厚和功能障碍。电镜观察显示9-PAHSA连续处理可显著增加db/db小鼠心肌细胞内自溶酶体的数量，同时显著减少心肌细胞内油脂的含量。此外，iTRAQ分析显示，继续9-PAHSA处理上调BAG 3和HSPB 8。Western blot分析证实9-PAHSA下调糖尿病心肌Akt/mTOR，激活PI 3 KIII/BECN 1复合物。因此，9-PAHSA通过改善颈动脉血管钙化、促进自噬通量和减少心肌肥大而有益于糖尿病小鼠的DCVD。
Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.
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影响因子：
3.7
作者：
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DOI：
10.1016/j.ecl.2013.09.007
发表时间：
2014-03-01
影响因子：
4.5
作者：
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影响因子：
4.5
作者：
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