《生命科学》 2026, 38(1): 163-181

肺动脉高压血管重构的自噬相关调控通路研究进展

贾成真¹ , 刘永胜² , 肖 娟¹ , 吴佳琦¹ , 范晓航^1,2,*

¹湖北文理学院基础医学院，襄阳 441053 ²湖北文理学院附属医院襄阳市中心医院心内科，心血管疾病 研究所，襄阳 441021

摘　要：

肺动脉高压（pulmonary hypertension，PH）是一种病因复杂的心肺系统疾病，以肺血管重构和肺血管阻力增高为特征，目前无法治愈。越来越多的研究显示PH与自噬失调密切相关，FoxO1、AMPK-mTOR-ULK1、NF-κB、PI3K/AKT/mTOR、ROS、LC3/Beclin-1、HIF-1α/BNIP3、BMPR2以及MAPK等自噬相关通路调控肺动脉平滑肌细胞（pulmonary artery smooth muscle cells，PASMCs）和肺动脉内皮细胞（pulmonary artery endothelial cells，PAECs）增殖或凋亡，进而调控肺血管重构，促进或改善PH。本文主要综述近年来自噬调节PH肺血管重构的相关信号通路。

通讯作者：范晓航 , Email:xiaohang0819@sina.com

Research progress on autophagy-related regulatory pathways of vascular remodeling in pulmonary hypertension

JIA Cheng-Zhen¹ , LIU Yong-Sheng² , XIAO Juan¹ , WU Jia-Qi¹ , FAN Xiao-Hang^1,2,*

¹School of Basic Medicine, Hubei University of Arts and Science, Xiangyang 441053, China ²Institute of Cardiovascular Diseases, Department of Cardiology, Xiang Yang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China

Abstract:

Pulmonary hypertension (PH) is a cardiopulmonary disease with complex etiology, characterized by progressively increasing pulmonary vascular resistance and pulmonary vascular remodeling. Currently, there is no cure for PH, highlighting an urgent clinical need for novel therapeutic targets to intervene in vascular remodeling. Recent research indicates that dysregulation of cellular autophagy plays a pivotal role in the pathogenesis and progression of PH. Autophagy, a highly conserved cellular self-degradation process, precisely regulates the proliferation, apoptosis, migration, and phenotypic switching of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) through multiple signaling pathways, thereby influencing the course of pulmonary vascular remodeling. This review aims to systematically elucidate the autophagy-related signaling pathways involved in pulmonary vascular remodeling. These pathways include, but are not limited to, the FoxO1, AMPK-mTOR-ULK1, NF-κB, PI3K/AKT/mTOR, ROS, LC3/Beclin-1, HIF-1α/BNIP3, BMPR2, and MAPK signaling pathways. These pathways form a complex regulatory network. Among them, the FoxO1 and AMPK-mTOR-ULK1 pathways primarily exert protective effects in pulmonary vascular remodeling. In contrast, the NF-κB, eIF2α, LC3/Beclin-1 pathways, oxidative stress, and BMPR2 mutations predominantly contribute to detrimental effects. The HIF-1α/BNIP3, PI3K/AKT/mTOR, and MAPK pathways can play dual roles, finely tuning abnormal PASMC proliferation, migration, and anti-apoptosis, as well as PAEC dysfunction and apoptosis. This intricate regulation ultimately drives or inhibits remodeling processes such as vascular wall thickening and lumen occlusion. Furthermore, this article reviews therapeutic strategies for PH targeting autophagy. By employing pharmacological interventions to either inhibit or promote cellular autophagy, vascular remodeling can be suppressed, thereby alleviating PH. For example, the mTOR inhibitor rapamycin, chloroquine, and hydroxychloroquine are utilized to inhibit autophagy clinically. In addition to drug-based approaches, gene therapy strategies can also be applied to regulate autophagy. Targeting genes such as miR-210, miR-138-5p, miRNA-205-5p, miR-204, and miR-382-3p can reduce the proliferation, differentiation, and anti-apoptotic activity of PASMCs, decrease medial hypertrophy in the pulmonary vasculature in experimental PH, and consequently attenuate pulmonary vascular remodeling. An in-depth exploration of the regulatory role of autophagy in pulmonary vascular remodeling will contribute to advancing research on the molecular mechanisms of PH and facilitate the development of autophagy-related therapeutics. It is believed that with further investigation into the molecular mechanisms of autophagy in PH, autophagy is likely to become a breakthrough point and a crucial target for the prevention and treatment of PH.

Communication Author：FAN Xiao-Hang , Email:xiaohang0819@sina.com