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作者

Mingjun Zhang Xiaobin Guo Jiaxing Zhang Xiangran Kong Hongyan Zhao Xianfei Guo Chunlin Wang Peng Tian null Keqing Hu

作者单位

¹Department of Cardiology (Chest Pain Center), Central Hospital, Shandong First Medical University, Jinan, Shandong, China

刊名

Scientific Reports

年份

2026

关键词

PHLPP1 Atherosclerosis VSMC Foam cell AMPK Autophagy

摘要

PH domain and leucine-rich repeat protein phosphatase1 is a recently identified serine/threonine protein phosphatase which plays a critical role in metabolic disorders through dephosphorylation of its downstream targets, but the association between PHLPP1 and atherosclerosis as well as vascular smooth muscle cell -derived foam cell formation remains poorly understood. This study investigates the function and mechanisms of PHLPP1 inhibition in atherosclerotic plaque progression and VSMC-derived ...更多

PH domain and leucine-rich repeat protein phosphatase1 is a recently identified serine/threonine protein phosphatase which plays a critical role in metabolic disorders through dephosphorylation of its downstream targets, but the association between PHLPP1 and atherosclerosis as well as vascular smooth muscle cell -derived foam cell formation remains poorly understood. This study investigates the function and mechanisms of PHLPP1 inhibition in atherosclerotic plaque progression and VSMC-derived foam cell formation. In vivo, the expression of PHLPP1 in ApoE mice was knocked down by lentivirus-mediated short hairpin RNA . HE staining, Oil Red O staining, immunohistochemistry and immunofluorescence of aortic sinus sections were performed. Similarly, in vitro, the expression of PHLPP1 was inhibited using PHLPP1-siRNA; and then the primary VSMCs were exposed to 80 µg/ml oxidized low-density lipoprotein for the following experiments. The expression of PHLPP1 was up-regulated in both atherosclerotic plaques and ox-LDL treated primary VSMCs. Furthermore, PHLPP1 inhibition ameliorated the atherosclerotic plaque formation in high-fat diet fed ApoE mice independent of LDL-C levels. Additionally, PHLPP1 knockdown reduced the lipid accumulation and improved the autophagy level in VSMCs mediated by activating AMPK signaling pathway, which could be blocked by 3-MA and compound C . Inhibition of PHLPP1 expression alleviates atherosclerotic plaque progression and ameliorates lipid deposition in VSMCs, an effect associated with enhanced autophagy mediated by increased AMPK phosphorylation in advanced atherosclerosis.收起

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