线粒体质量控制网络失衡在肺动脉高压中的 作用机制及治疗前景
Mechanisms and Therapeutic Prospects of Mitochondrial Quality Control Network Imbalance in Pulmonary Arterial Hypertension
DOI: 10.12677/acm.2026.1631154, PDF,   
作者: 单红光, 唐任绮, 平松鹤：绍兴大学医学院，浙江 绍兴；叶 涵：浙江大学医学院，浙江 杭州；何 梦*：绍兴市人民医院呼吸与危重症医学科，浙江 绍兴
关键词: 肺动脉高压；线粒体动力学；线粒体代谢重编程；线粒体自噬；靶向治疗；Pulmonary Arterial Hypertension； Mitochondrial Dynamics； Mitochondrial Metabolic Reprogramming； Mitophagy； Targeted Therapy
摘要: 肺动脉高压(PAH)是以肺血管重构和肺动脉压进行性升高为特征的致命性疾病，其发病机制尚未完全阐明。线粒体作为能量代谢、氧化还原稳态及程序性死亡调控的核心细胞器，在PAH的发生发展中发挥关键调控作用。线粒体动力学失衡(分裂增强、融合受损)、代谢重编程(糖酵解优势)及线粒体自噬调控异常并非孤立事件，而是通过“动力学–代谢–自噬”恶性循环闭环协同重塑肺动脉平滑肌细胞(PASMCs)和肺动脉内皮细胞(PAECs)的增殖、凋亡与代谢表型，驱动血管重构。本文从系统生物学视角，整合线粒体质量控制三大核心机制在PAH中的交互网络，梳理靶向该网络的潜在干预策略及最新临床转化进展，以期为PAH的机制研究和临床精准治疗提供新思路。
Abstract: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by pulmonary vascular remodeling and a progressive increase in pulmonary arterial pressure, the pathogenesis of which has not yet been fully elucidated. Mitochondria, as core organelles regulating energy metabolism, redox homeostasis, and programmed cell death, play a critical regulatory role in the occurrence and development of PAH. The imbalance in mitochondrial dynamics (enhanced fission, impaired fusion), metabolic reprogramming (glycolytic shift), and dysregulated mitophagy are not isolated events. Instead, they synergistically reshape the proliferation, apoptosis, and metabolic phenotypes of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) through a closed-loop “dynamics-metabolism-mitophagy” vicious cycle, driving vascular remodeling. From a systems biology perspective, this article integrates the interactive network of the three core mechanisms of mitochondrial quality control in PAH, reviews potential intervention strategies targeting this network, and discusses the latest advances in clinical translation, aiming to provide new insights into the mechanistic study and precision clinical treatment of PAH.
文章引用：单红光, 唐任绮, 平松鹤, 叶涵, 何梦. 线粒体质量控制网络失衡在肺动脉高压中的 作用机制及治疗前景[J]. 临床医学进展, 2026, 16(3): 3479-3490. https://doi.org/10.12677/acm.2026.1631154

参考文献

[1] Knoepp, F., Abid, S., Houssaini, A., Lipskaia, L., Gökyildirim, M.Y., Born, E., et al. (2025) Piezo1 in PASMCs: Critical for Hypoxia-Induced Pulmonary Hypertension Development. Circulation Research, 136, 1031-1048. [Google Scholar] [CrossRef] [PubMed]
[2] Mocumbi, A., Humbert, M., Saxena, A., Jing, Z., Sliwa, K., Thienemann, F., et al. (2024) Pulmonary Hypertension. Nature Reviews Disease Primers, 10, Article No. 1. [Google Scholar] [CrossRef] [PubMed]
[3] Anand, V., Roy, S.S., Archer, S.L., Weir, E.K., Garg, S.K., Duval, S., et al. (2016) Trends and Outcomes of Pulmonary Arterial Hypertension-Related Hospitalizations in the United States: Analysis of the Nationwide Inpatient Sample Database from 2001 through 2012. JAMA Cardiology, 1, 1021-1029. [Google Scholar] [CrossRef] [PubMed]
[4] Marsboom, G., Toth, P.T., Ryan, J.J., Hong, Z., Wu, X., Fang, Y., et al. (2012) Dynamin-Related Protein 1-Mediated Mitochondrial Mitotic Fission Permits Hyperproliferation of Vascular Smooth Muscle Cells and Offers a Novel Therapeutic Target in Pulmonary Hypertension. Circulation Research, 110, 1484-1497. [Google Scholar] [CrossRef] [PubMed]
[5] Zhang, L., Ma, C., Zhang, C., Ma, M., Zhang, F., Zhang, L., et al. (2016) Reactive Oxygen Species Effect Pasmcs Apoptosis via Regulation of Dynamin-Related Protein 1 in Hypoxic Pulmonary Hypertension. Histochemistry and Cell Biology, 146, 71-84. [Google Scholar] [CrossRef] [PubMed]
[6] Parra, V., Bravo-Sagua, R., Norambuena-Soto, I., Hernández-Fuentes, C.P., Gómez-Contreras, A.G., Verdejo, H.E., et al. (2017) Inhibition of Mitochondrial Fission Prevents Hypoxia-Induced Metabolic Shift and Cellular Proliferation of Pulmonary Arterial Smooth Muscle Cells. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1863, 2891-2903. [Google Scholar] [CrossRef] [PubMed]
[7] Humbert, M., Kovacs, G., Hoeper, M.M., et al. (2023) 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. European Respiratory Journal, 43, 3618-3731.
[8] Young, J.M., Williams, D.R. and Thompson, A.A.R. (2019) Thin Air, Thick Vessels: Historical and Current Perspectives on Hypoxic Pulmonary Hypertension. Frontiers in Medicine (Lausanne), 6, Article No. 93. [Google Scholar] [CrossRef] [PubMed]
[9] Thenappan, T., Ormiston, M.L., Ryan, J.J. and Archer, S.L. (2018) Pulmonary Arterial Hypertension: Pathogenesis and Clinical Management. BMJ, 360, j5492. [Google Scholar] [CrossRef] [PubMed]
[10] 李涵飞, 祝田田, 赵繁荣, 等. 肺动脉高压发病机制及治疗研究进展[J]. 新乡医学院学报, 2025, 42(5): 426-431.
[11] Cuthbertson, I., Morrell, N.W. and Caruso, P. (2023) bmpr2 Mutation and Metabolic Reprogramming in Pulmonary Arterial Hypertension. Circulation Research, 132, 109-126. [Google Scholar] [CrossRef] [PubMed]
[12] Mitra, A., Yi, D., Dai, Z. and de Jesus Perez, V. (2024) Unraveling the Role of HIF and Epigenetic Regulation in Pulmonary Arterial Hypertension: Implications for Clinical Research and Its Therapeutic Approach. Frontiers in Medicine, 11, Article ID: 1460376. [Google Scholar] [CrossRef] [PubMed]
[13] Hu, Y., Chi, L., Kuebler, W.M. and Goldenberg, N.M. (2020) Perivascular Inflammation in Pulmonary Arterial Hypertension. Cells, 9, Article No. 2338. [Google Scholar] [CrossRef] [PubMed]
[14] Vazquez, Z.G.S. and Klinger, J.R. (2020) Guidelines for the Treatment of Pulmonary Arterial Hypertension. Lung, 198, 581-596. [Google Scholar] [CrossRef] [PubMed]
[15] Spiekerkoetter, E., Kawut, S.M. and de Jesus Perez, V.A. (2019) New and Emerging Therapies for Pulmonary Arterial Hypertension. Annual Review of Medicine, 70, 45-59. [Google Scholar] [CrossRef] [PubMed]
[16] Santos-Gallego, C.G. and Badimón, J.J. (2015) Catheter-Based Renal Denervation as a Treatment for Pulmonary Hyper-tension: Hope or Hype? Revista Española de Cardiología, 68, 551-553. [Google Scholar] [CrossRef] 
[17] Meyer, J.N., Leuthner, T.C. and Luz, A.L. (2017) Mitochondrial Fusion, Fission, and Mitochondrial Toxicity. Toxicology, 391, 42-53. [Google Scholar] [CrossRef] [PubMed]
[18] Hall, A.R., Burke, N., Dongworth, R.K. and Hausenloy, D.J. (2014) Mitochondrial Fusion and Fission Proteins: Novel Therapeutic Targets for Combating Cardiovascular Disease. British Journal of Pharmacology, 171, 1890-1906. [Google Scholar] [CrossRef] [PubMed]
[19] Chan, D.C. (2020) Mitochondrial Dynamics and Its Involvement in Disease. Annual Review of Pathology: Mechanisms of Disease, 15, 235-259. [Google Scholar] [CrossRef] [PubMed]
[20] Feng, W., Wang, J., Yan, X., Zhang, Q., Chai, L., Wang, Q., et al. (2021) ERK/Drp1‐Dependent Mitochondrial Fission Contributes to HMGB1‐Induced Autophagy in Pulmonary Arterial Hypertension. Cell Proliferation, 54, e13048. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, F., Zhen, Y., Si, C., Wang, C., Pan, L., Chen, Y., et al. (2021) WNT5B Promotes Vascular Smooth Muscle Cell Dedifferentiation via Mitochondrial Dynamics Regulation in Chronic Thromboembolic Pulmonary Hypertension. Journal of Cellular Physiology, 237, 789-803. [Google Scholar] [CrossRef] [PubMed]
[22] Xu, W. and Erzurum, S.C. (2011) Endothelial Cell Energy Metabolism, Proliferation, and Apoptosis in Pulmonary Hypertension. Comprehensive Physiology, 1, 357-372. [Google Scholar] [CrossRef] 
[23] Suresh, K., Servinsky, L., Jiang, H., Bigham, Z., Zaldumbide, J., Huetsch, J.C., et al. (2019) Regulation of Mitochondrial Fragmentation in Microvascular Endothelial Cells Isolated from the Su5416/Hypoxia Model of Pulmonary Arterial Hypertension. American Journal of Physiology-Lung Cellular and Molecular Physiology, 317, L639-L652. [Google Scholar] [CrossRef] [PubMed]
[24] Liang, S., Yegambaram, M., Wang, T., Wang, J., Black, S.M. and Tang, H. (2022) Mitochondrial Metabolism, Redox, and Calcium Homeostasis in Pulmonary Arterial Hypertension. Biomedicines, 10, Article No. 341. [Google Scholar] [CrossRef] [PubMed]
[25] Fang, X., Chen, X., Zhong, G., Chen, Q. and Hu, C. (2016) Mitofusin 2 Downregulation Triggers Pulmonary Artery Smooth Muscle Cell Proliferation and Apoptosis Imbalance in Rats with Hypoxic Pulmonary Hypertension via the PI3K/Akt and Mitochondrial Apoptosis Pathways. Journal of Cardiovascular Pharmacology, 67, 164-174. [Google Scholar] [CrossRef] [PubMed]
[26] 温敬利, 李甜甜, 石莉程, 等. 线粒体动力学在肺动脉高压发病机制中的研究进展[J]. 临床肺科杂志, 2022, 27(8): 1233-1237.
[27] Chen, K., Dasgupta, A., Lin, J., Potus, F., Bonnet, S., Iremonger, J., et al. (2018) Epigenetic Dysregulation of the Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increases Mitotic Mitochondrial Fission and Promotes Pulmonary Arterial Hypertension. Circulation, 138, 287-304. [Google Scholar] [CrossRef] [PubMed]
[28] Wang, J., Chen, X., Zhang, H., et al. (2024) DNA Hypomethylation of MiD49/51 Promoters Drives Sustained Mitochondrial Fission in Pulmonary Arterial Hypertension. Clinical Epigenetics, 16, Article No. 45.
[29] Li, B., Zhu, Y., Sun, Q., Yu, C., Chen, L., Tian, Y., et al. (2018) Reversal of the Warburg Effect with DCA in PDGF-Treated Human PASMC Is Potentiated by Pyruvate Dehydrogenase Kinase-1 Inhibition Mediated through Blocking Akt/GSK-3β Signalling. International Journal of Molecular Medicine, 42, 1391-1400. [Google Scholar] [CrossRef] [PubMed]
[30] Rafikov, R., Sun, X., Rafikova, O., Louise Meadows, M., Desai, A.A., Khalpey, Z., et al. (2015) Complex I Dysfunction Underlies the Glycolytic Switch in Pulmonary Hypertensive Smooth Muscle Cells. Redox Biology, 6, 278-286. [Google Scholar] [CrossRef] [PubMed]
[31] Michelakis, E.D., Gurtu, V., Webster, L., Barnes, G., Watson, G., Howard, L., et al. (2017) Inhibition of Pyruvate Dehydrogenase Kinase Improves Pulmonary Arterial Hypertension in Genetically Susceptible Patients. Science Translational Medicine, 9, eaao4583. [Google Scholar] [CrossRef] [PubMed]
[32] Korde, A.S., Yadav, V.R., Zheng, Y. and Wang, Y. (2011) Primary Role of Mitochondrial Rieske Iron-Sulfur Protein in Hypoxic ROS Production in Pulmonary Artery Myocytes. Free Radical Biology and Medicine, 50, 945-952. [Google Scholar] [CrossRef] [PubMed]
[33] Rafikova, O., Srivastava, A., Desai, A.A., Rafikov, R. and Tofovic, S.P. (2018) Recurrent Inhibition of Mitochondrial Complex III Induces Chronic Pulmonary Vasoconstriction and Glycolytic Switch in the Rat Lung. Respiratory Research, 19, Article No. 69. [Google Scholar] [CrossRef] [PubMed]
[34] Baertling, F., Al-Murshedi, F., Sánchez-Caballero, L., Al-Senaidi, K., Joshi, N.P., Venselaar, H., et al. (2017) Mutation in Mitochondrial Complex IV Subunit COX5A Causes Pulmonary Arterial Hypertension, Lactic Acidemia, and Failure to Thrive. Human Mutation, 38, 692-703. [Google Scholar] [CrossRef] [PubMed]
[35] 徐燕, 杨朝, 耑冰. 细胞程序性死亡在肺动脉高压中的研究进展: 自噬、焦亡、铁死亡[J]. 临床肺科杂志, 2023, 28(8): 1247-1250.
[36] Dromparis, P., Paulin, R., Stenson, T.H., Haromy, A., Sutendra, G. and Michelakis, E.D. (2013) Attenuating Endoplasmic Reticulum Stress as a Novel Therapeutic Strategy in Pulmonary Hypertension. Circulation, 127, 115-125. [Google Scholar] [CrossRef] [PubMed]
[37] 崔志峰, 孙佳伟, 刘美洋, 等. 线粒体功能障碍在肺动脉高压形成中的作用机制[J]. 实用心脑肺血管病杂志, 2022, 30(7): 24-28.
[38] Egnatchik, R.A., Brittain, E.L., Shah, A.T., Fares, W.H., Ford, H.J., Monahan, K., et al. (2017) Dysfunctional BMPR2 Signaling Drives an Abnormal Endothelial Requirement for Glutamine in Pulmonary Arterial Hypertension. Pulmonary Circulation, 7, 186-199. [Google Scholar] [CrossRef] [PubMed]
[39] Kim, B., Li, J., Jang, C. and Arany, Z. (2017) Glutamine Fuels Proliferation but Not Migration of Endothelial Cells. The EMBO Journal, 36, 2321-2333. [Google Scholar] [CrossRef] [PubMed]
[40] Rhodes, C.J., Ghataorhe, P., Wharton, J., Rue-Albrecht, K.C., Hadinnapola, C., Watson, G., et al. (2017) Plasma Metabolomics Implicates Modified Transfer RNAs and Altered Bioenergetics in the Outcomes of Pulmonary Arterial Hypertension. Circulation, 135, 460-475. [Google Scholar] [CrossRef] [PubMed]
[41] Zhao, Y.D., Chu, L., Lin, K., Granton, E., Yin, L., Peng, J., et al. (2015) A Biochemical Approach to Understand the Pathogenesis of Advanced Pulmonary Arterial Hypertension: Metabolomic Profiles of Arginine, Sphingosine-1-Phosphate, and Heme of Human Lung. PLOS ONE, 10, e0134958. [Google Scholar] [CrossRef] [PubMed]
[42] Chen, J., Tang, H., Sysol, J.R., Moreno-Vinasco, L., Shioura, K.M., Chen, T., et al. (2014) The Sphingosine Kinase 1/Sphingosine-1-Phosphate Pathway in Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine, 190, 1032-1043. [Google Scholar] [CrossRef] [PubMed]
[43] Singh, N., Manhas, A., Kaur, G., Jagavelu, K. and Hanif, K. (2016) Inhibition of Fatty Acid Synthase Is Protective in Pulmonary Hypertension. British Journal of Pharmacology, 173, 2030-2045. [Google Scholar] [CrossRef] [PubMed]
[44] Brittain, E.L., Talati, M., Fessel, J.P., Zhu, H., Penner, N., Calcutt, M.W., et al. (2016) Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension. Circulation, 133, 1936-1944. [Google Scholar] [CrossRef] [PubMed]
[45] Chen, C., Luo, F., Wu, P., Huang, Y., Das, A., Chen, S., et al. (2020) Metabolomics Reveals Metabolite Changes of Patients with Pulmonary Arterial Hypertension in China. Journal of Cellular and Molecular Medicine, 24, 2484-2496. [Google Scholar] [CrossRef] [PubMed]
[46] Zheng, H., Zhao, J., Yan, Y., Lian, T., Ye, J., Wang, X., et al. (2018) Metabolic Reprogramming of the Urea Cycle Pathway in Experimental Pulmonary Arterial Hypertension Rats Induced by Monocrotaline. Respiratory Research, 19, Article No. 94. [Google Scholar] [CrossRef] [PubMed]
[47] Ba, H., Guo, Y., Jiang, Y., Li, Y., Dai, X., Liu, Y., et al. (2024) Unveiling the Metabolic Landscape of Pulmonary Hypertension: Insights from Metabolomics. Respiratory Research, 25, Article No. 221. [Google Scholar] [CrossRef] [PubMed]
[48] Vander Heiden, M.G. and DeBerardinis, R.J. (2017) Understanding the Intersections between Metabolism and Cancer Biology. Cell, 168, 657-669. [Google Scholar] [CrossRef] [PubMed]
[49] Patra, K.C. and Hay, N. (2014) The Pentose Phosphate Pathway and Cancer. Trends in Biochemical Sciences, 39, 347-354. [Google Scholar] [CrossRef] [PubMed]
[50] Kassa, B., Kumar, R., Mickael, C., Sanders, L., Vohwinkel, C., Lee, M.H., et al. (2021) Endothelial Cell PHD2-HIF1α-PFKFB3 Contributes to Right Ventricle Vascular Adaptation in Pulmonary Hypertension. American Journal of Physiology-Lung Cellular and Molecular Physiology, 321, L675-L685. [Google Scholar] [CrossRef] [PubMed]
[51] Stine, Z.E., Schug, Z.T., Salvino, J.M. and Dang, C.V. (2021) Targeting Cancer Metabolism in the Era of Precision Oncology. Nature Reviews Drug Discovery, 21, 141-162. [Google Scholar] [CrossRef] [PubMed]
[52] Huang, W., Zheng, R., Gong, L., Zhang, Y., Tan, J., Cao, X., et al. (2025) Roles of Lipid Metabolism in Pulmonary Hypertension: Friend or Foe? Biomolecules, 15, Article No. 1679. [Google Scholar] [CrossRef] 
[53] Drozdov, I. and Molkentin, J.D. (2020) Mitochondrial Calcium in Health and Disease. Nature Reviews Molecular Cell Biology, 21, 22-40.
[54] 张晓静, 李晓燕, 成其发, 等. 线粒体钠钙交换蛋白在心血管疾病发生发展中的作用研究进展[J]. 山东医药, 2022, 62(23): 104-107.
[55] Dixon, S.J., Lemberg, K.M., Lamprecht, M.R., Skouta, R., Zaitsev, E.M., Gleason, C.E., et al. (2012) Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death. Cell, 149, 1060-1072. [Google Scholar] [CrossRef] [PubMed]
[56] Yang, W.S., SriRamaratnam, R., Welsch, M.E., Shimada, K., Skouta, R., Viswanathan, V.S., et al. (2014) Regulation of Ferroptotic Cancer Cell Death by GPX4. Cell, 156, 317-331. [Google Scholar] [CrossRef] [PubMed]
[57] Nie, X., et al. (2022) Ferroptosis: A New Regulatory Mechanism in Cardiovascular Disease. Journal of Cellular and Molecular Medicine, 26, 1353-1362.
[58] Wang, D., Zhu, Z., Lin, D., Zheng, S., Chuang, K., Gui, L., et al. (2021) Magnesium Supplementation Attenuates Pulmonary Hypertension via Regulation of Magnesium Transporters. Hypertension, 77, 617-631. [Google Scholar] [CrossRef] [PubMed]
[59] Wolf, F.I. and Trapani, V. (2007) Cell (Patho)physiology of Magnesium. Clinical Science, 114, 27-35. [Google Scholar] [CrossRef] [PubMed]
[60] Tangvoraphonkchai, K. and Davenport, A. (2018) Magnesium and Cardiovascular Disease. Advances in Chronic Kidney Disease, 25, 251-260. [Google Scholar] [CrossRef] [PubMed]
[61] Pelczyńska, M., Moszak, M. and Bogdański, P. (2022) The Role of Magnesium in the Pathogenesis of Metabolic Disorders. Nutrients, 14, Article No. 1714. [Google Scholar] [CrossRef] [PubMed]
[62] Zhao, L., Oliver, E., Maratou, K., Atanur, S.S., Dubois, O.D., Cotroneo, E., et al. (2015) The Zinc Transporter ZIP12 Regulates the Pulmonary Vascular Response to Chronic Hypoxia. Nature, 524, 356-360. [Google Scholar] [CrossRef] [PubMed]
[63] Kambe, T., Tsuji, T., Hashimoto, A. and Itsumura, N. (2015) The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism. Physiological Reviews, 95, 749-784. [Google Scholar] [CrossRef] [PubMed]
[64] Ye, C., Lian, G., Wang, T., Chen, A., Chen, W., Gong, J., et al. (2022) The Zinc Transporter ZIP12 Regulates Monocrotaline-Induced Proliferation and Migration of Pulmonary Arterial Smooth Muscle Cells via the AKT/ERK Signaling Pathways. BMC Pulmonary Medicine, 22, Article No. 111. [Google Scholar] [CrossRef] [PubMed]
[65] Durcan, T.M. and Fon, E.A. (2015) The Three P’s of Mitophagy: PARKIN, PINK1, and Post-Translational Modifications. Genes & Development, 29, 989-999. [Google Scholar] [CrossRef] [PubMed]
[66] 陈辛玲, 王生兰. 细胞自噬过程、通路、调控及其与肺动脉高压的多重相关性[J]. 中国组织工程研究, 2021, 25(21): 3414-3420.
[67] 曹琼雯, 赵明旺, 王凤儒. 基于PINK1/Parkin介导的线粒体自噬探讨中西医防治MIRI的研究进展[J]. 中国实验方剂学杂志, 2025: 1-16.
[68] 杨姿. 靶向自噬途径对肺动脉高压的治疗作用与机制研究[D]: [硕士学位论文]. 广州: 广州医科大学, 2023.
[69] Liu, X., et al. (2020) Mitochondrial Dynamics in Pulmonary Arterial Hypertension: Mechanisms and Therapeutic Opportunities. Pharmacology & Therapeutics, 213, Article ID: 107576.
[70] Li, C., et al. (2022) BNIP3-Mediated Mitophagy Protects against Pulmonary Arterial Smooth Muscle Cell Proliferation via Maintaining Mitochondrial Homeostasis. Cell Death Discovery, 8, 462.
[71] 朱宇帆, 白茜文, 易舒婷, 等. 巨噬细胞在肺动脉高压发病中的机制及研究进展[J]. 广州医科大学学报, 2021, 49(4): 101-105.
[72] Sun, Y., et al. (2022) BNIP3-Mediated Mitophagy Exacerbates Endothelial Dysfunction in Pulmonary Arterial Hypertension via Excessive Mitochondrial Clearance. Cell Death & Disease, 13, 78.
[73] Wang, X., et al. (2023) FUNDC1 Silencing Protects against Endothelial Dysfunction in Pulmonary Arterial Hypertension by Balancing Mitophagy. Free Radical Biology and Medicine, 195, Article ID: 113248.
[74] Chen, S., et al. (2023) Ginsenoside Rg3 Ameliorates Hypoxic Pulmonary Arterial Hypertension by Promoting FUNDC1-Mediated Mitophagy. Phytomedicine, 114, Article ID: 155388.
[75] Li, X., et al. (2021) Drp1 Inhibition Restores Mitophagy and Attenuates Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension. Antioxidants & Redox Signaling, 35, 1133-1149.
[76] Wang, Y., et al. (2018) Mfn2 Regulates Mitophagy through Interacting with Parkin in Pulmonary Arterial Smooth Muscle Cells. American Journal of Physiology. Lung Cellular and Molecular Physiology, 315, L1120-L1132.
[77] 刘思宇, 王岚, 李为民. BMPR2基因突变与线粒体功能异常在肺动脉高压中的交互作用[J]. 中国呼吸与危重监护杂志, 2023, 22(2): 155-160.
[78] 钟睿, 赵丹麦, 王晓天, 等. 中医药调控线粒体动力学治疗糖尿病肾病[J/OL]. 中医学报, 2025: 1-12.
https://link.cnki.net/urlid/41.1411.R.20250225.1900.058, 2025-02-26.
[79] Zhou, X., et al. (2024) The Double-Edged Sword of Mitophagy in Cardiovascular Diseases: Therapeutic Opportunities and Challenges. Journal of Molecular and Cellular Cardiology, 190, Article ID: 105272.
[80] 黄国阳, 徐晨宇, 刘璋璐, 等. 线粒体自噬在低氧性肺动脉高压中的作用及研究进展[J]. 心脏杂志, 2025, 37(2): 198-203.
[81] Zhang, H., et al. (2024) Mito-Rapa: A Mitochondria-Targeted Rapamycin Derivative for Selective Activation of Mitophagy in Pulmonary Arterial Hypertension. Acta Pharmaceutica Sinica B, 14, 1623-1636.
[82] 张超, 易健, 丁蓉珍, 等. 肺心汤通过调控AMPK/mTOR信号通路抑制自噬对低氧性肺动脉高压大鼠的保护作用[J]. 湖南中医药大学学报, 2024, 44(5): 744-753.
[83] Wang, J., et al. (2023) Combination Therapy of Mdivi-1 and PINK1 Activator Improves Mitophagy Efficiency in Pulmonary Arterial Hypertension. Journal of Cardiovascular Pharmacology, 82, 241-252.
[84] Zhang, L.M., Ji, L., Tang, X.H., et al. (2015) Inhibition to DRP1 Translocation Can Mitigate p38 MAPK-Signaling Pathway Activation in GMC Induced by Hyperglycemia. Renal Failure, 37, 743-750.
[85] Smith, A.M. and Murphy, M.P. (2020) Mitochondrial Targeting of Small Molecules for Reducing Off-Target Effects in Metabolic Disease. Antioxidants & Redox Signaling, 32, 1089-1102.
[86] Yan, L., Luo, X., Hang, C., Wang, Y., Zhang, Z., Xu, S., et al. (2024) Unraveling the Mfn2-Warburg Effect Nexus: A Therapeutic Strategy to Combat Pulmonary Arterial Hypertension Arising from Catch-Up Growth after IUGR. Respiratory Research, 25, Article No. 328. [Google Scholar] [CrossRef] [PubMed]
[87] Li, L., Wang, X., Wang, L., Qu, L., Zhu, X., Li, M., et al. (2015) Mammalian Target of Rapamycin Overexpression Antagonizes Chronic Hypoxia-Triggered Pulmonary Arterial Hypertension via the Autophagic Pathway. International Journal of Molecular Medicine, 36, 316-322. [Google Scholar] [CrossRef] [PubMed]
[88] Zhu, Y., Bai, X., Yi, S., et al. (2021) Mechanisms and Research Progress of Macrophages in the Pathogenesis of Pulmonary Hypertension. Journal of Guangzhou Medical University, 49, 120-126.
[89] Sharma, S., Aldhahri, A., Ratajczak, P., et al. (2021) Mitochondrial-Targeted Antioxidant MitoQ Reverses Mechano-Hypoxia Induced Endothelial Dysfunction in a Large Animal Model of Increased Pulmonary Blood Flow. American Journal of Physiology-Lung Cellular and Molecular Physiology, 321, L176-L186.
[90] Jorna, L.M., Nakládal, D., van Heuveln, J.N., van der Feen, D.E., Hagdorn, Q.A.J., Bossers, G.P.L., et al. (2025) SUL-150 Limits Vascular Remodeling and Ventricular Failure in Pulmonary Arterial Hypertension. International Journal of Molecular Sciences, 26, 7181. [Google Scholar] [CrossRef] [PubMed]
[91] Liao, Z. and He, Y. (2025) Exploring the Interplay between Mitochondria and Endoplasmic Reticulum in Pulmonary Arterial Hypertension. Frontiers in Cardiovascular Medicine, 12, Article ID: 1623775. [Google Scholar] [CrossRef] 
[92] Xia, N., Li, Y., Zhang, L., et al. (2025) Empagliflozin Improves Mitochondrial Biogenesis and Ameliorates Experimental Pulmonary Vascular Remodeling, but May Not Benefit Patients with Pulmonary Arterial Hypertension.

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