Institute of Cardiovascular Research, Xinqiao Hospital, Army Medical University, Chongqing 400037, China.
Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China.
Oxid Med Cell Longev. 2022 Oct 26;2022:7192507. doi: 10.1155/2022/7192507. eCollection 2022.
Vascular calcification (VC) is regarded as a common feature of vascular aging. Klotho deficiency reportedly contributes to VC, which can be ameliorated by restoration of Klotho expression. However, the specific mechanisms involved remain unclear. Here, we investigated the role of autophagy in the process of Klotho-inhibiting VC. The clinical study results indicated that, based on Agatston score, serum Klotho level was negatively associated with aortic calcification. Then, Klotho-deficient mice exhibited aortic VC, which could be alleviated with the supplementation of Klotho protein. Moreover, autophagy increased in the aorta of Klotho-deficient mice and protected against VC. Finally, we found that Klotho ameliorated calcification by promoting autophagy both in the aorta of Klotho-deficient mice and in mouse vascular smooth muscle cells (MOVAS) under calcifying conditions. These findings indicate that Klotho deficiency induces increased autophagy to protect against VC and that Klotho expression further enhances autophagy to ameliorate calcification. This study is beneficial to exploring the underlying mechanisms of Klotho regulating VC, which has important guiding significance for future clinical studies in the treatment of VC.
血管钙化（VC）被认为是血管老化的共同特征。据报道，Klotho 缺乏会导致 VC，而 Klotho 表达的恢复可以改善 VC。然而，具体的机制尚不清楚。在这里，我们研究了自噬在 Klotho 抑制 VC 过程中的作用。临床研究结果表明，根据 Agatston 评分，血清 Klotho 水平与主动脉钙化呈负相关。然后，Klotho 缺陷型小鼠表现出主动脉 VC，而 Klotho 蛋白的补充可以缓解这种情况。此外，自噬在 Klotho 缺陷型小鼠的主动脉中增加，并能防止 VC。最后，我们发现 Klotho 通过促进自噬来改善 Klotho 缺陷型小鼠主动脉和钙化条件下的小鼠血管平滑肌细胞（MOVAS）中的钙化。这些发现表明，Klotho 缺乏会诱导增加的自噬来保护免受 VC，并且 Klotho 表达进一步增强自噬来改善钙化。这项研究有助于探索 Klotho 调节 VC 的潜在机制，对未来治疗 VC 的临床研究具有重要的指导意义。
