王金宇, 赵悦孚, 赵恩麒, 盖祥云*. 低氧诱导钙超载致肺动脉重构的机制J. 药学学报, 2021,56(8): 2164-2168. doi: 10.16438/j.0513-4870.2021-0627
引用本文: 王金宇, 赵悦孚, 赵恩麒, 盖祥云*. 低氧诱导钙超载致肺动脉重构的机制J. 药学学报, 2021,56(8): 2164-2168. doi: 10.16438/j.0513-4870.2021-0627
WANG Jin-yu, ZHAO Yue-fu, ZHAO En-qi, GAI Xiang-yun*. Mechanism of pulmonary artery remodeling induced by calcium overload induced by hypoxiaJ. Acta Pharmaceutica Sinica, 2021,56(8): 2164-2168. doi: 10.16438/j.0513-4870.2021-0627
Citation: WANG Jin-yu, ZHAO Yue-fu, ZHAO En-qi, GAI Xiang-yun*. Mechanism of pulmonary artery remodeling induced by calcium overload induced by hypoxiaJ. Acta Pharmaceutica Sinica, 2021,56(8): 2164-2168. doi: 10.16438/j.0513-4870.2021-0627

低氧诱导钙超载致肺动脉重构的机制

Mechanism of pulmonary artery remodeling induced by calcium overload induced by hypoxia

  • 摘要: 低氧性肺动脉高压(hypoxia pulmonary hypertension,HPH)是一种不可逆的疾病,HPH患者常伴有呼吸困难和乏力头痛,随着病情的发展,右心室逐渐衰竭最终导致死亡。低氧性肺血管重构是HPH的重要病理基础,重构的肺血管会形成永久性增厚。低氧性肺血管重构的机制较为复杂,目前市面上针对肺血管重构治疗药物研究甚少,主要停留在缓解肺血管收缩的层面。研究发现低氧会诱导肺动脉平滑肌细胞(pulmonary artery smooth musclecells,PASMCs)内发生钙超载从而引起PASMCs增殖,其主要机制包括低氧所导致的:①钙泵的异常表达;②肺动脉平滑肌细胞质膜钙通道的异常开放;③细胞钙敏感受体过表达;④钠钙交换蛋白表达异常。本文总结了以上低氧诱发钙超载从而导致肺动脉重构的机制,希望能为治疗HPH提供新的思路。

     

    Abstract: Patients with hypoxia pulmonary hypertension (HPH) are often accompanied by dyspnea, fatigue, and headache. With the development of the disease, the right ventricle gradually collapses and eventually leads to death. Hypoxic pulmonary vascular remodeling is an important pathological basis of HPH, and the remodeled pulmonary vessels will form permanent thickening. The mechanism of hypoxic pulmonary vascular remodeling is relatively complex. At present, there are few studies on drugs for pulmonary vascular remodeling on the market, mainly focusing on the alleviation of pulmonary vasoconstriction. It was found that hypoxia induces calcium overload in pulmonary artery smooth muscle cells (PASMCs), resulting in the proliferation of PASMCs. The main mechanisms include:① abnormal expression of calcium pumps; ② abnormal calcium channels in the plasma membrane of pulmonary artery smooth muscle cells; ③ overexpression of calcium-sensitive receptors in cells; ④ the expression of Na+/Ca2+ exchanger type-1 was abnormal. This review summarized several mechanisms of hypoxia induced calcium overload leading to pulmonary artery remodeling, hoping to provide a new idea for the treatment of HPH.

     

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