ArticleMolecular biology reports2023
PDK1 upregulates PINK1-mediated pulmonary endothelial cell mitophagy during hypoxia-induced pulmonary vascular remodeling.
Article in Molecular biology reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Mitophagy in cardiovascular diseases: a literature review.Cardiovascular diagnosis and therapy · 2026Review
- SIRT5 Inhibits Mitophagy and Inflammation of Hypoxia-Induced Pulmonary Hypertension by Regulating the Desuccinylation of PDK1.Molecular biotechnology · 2026Article
- Mitochondrial quality control mechanisms as molecular targets for impaired lung development: from fetuses to neonates.Respiratory research · 2025Review
- PINK1/Parkin Deficiency Enhances Vascular Remodeling and Aggravates Hypoxia-induced Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses.Apoptosis : an international journal on programmed cell death · 2025Review
- The Role of Endothelial Cell Mitophagy in Age-Related Cardiovascular Diseases.Aging and disease · 2024Review
- Copper homeostasis dysregulation in respiratory diseases: a review of current knowledge.Frontiers in physiology · 2024Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHypoxic pulmonary hypertension (HPH) is a complication of lung diseases with pulmonary vascular remodeling, although the underlying molecular mechanisms have not been fully elucidated. This study investigated the underlying molecular events by using a rat HPH model and primary pulmonary microvascular endothelial cells (PMVECs). METHODS AND
resultsThis study first established a rat HPH model and cultured PMVECs for transmission electron microscopic analysis and manipulation of 3-phosphoinositide-dependent protein kinase 1 (PDK1) or phosphatase and tensin homolog-induced kinase 1 (PINK1) expression in vitro. After that, the cell viability was assessed and the expression of different proteins was assayed using cell viability and western blot assays, respectively. Reactive oxygen species production, apoptosis, NLR family pyrin domain containing 3 (NLRP3) expression, and the levels of interleukin (IL)-1β, IL-6, and IL-8 were also assessed, while the interaction of PDK1 and PINK1 was determined using co-immunoprecipitation/western blot assays. Hypoxia induced mitophagy in the PMVECs and upregulated PINK1/Parkin expression, whereas knockdown of PINK1 expression under hypoxic conditions inhibited cell proliferation but induced endothelial cell apoptosis in vitro, decreased reactive oxygen species production and NLRP3 expression, and reduced the levels of inflammatory factors in PMVECs. However, hypoxia induced PDK1 expression, whereas knockdown of PDK1 downregulated PINK1 expression. Furthermore, treatment of the model rats with the PDK1 inhibitor dichloroacetate (DCA) was able to decrease PINK1 expression. In addition, the PDK1 and PINK1 proteins could interact with each other in the mitochondria of PMVECs to regulate the cell viability.
conclusionsThis study revealed that PDK1 induced PMVEC proliferation but inhibited their apoptosis to participate in pulmonary vascular remodeling, ultimately leading to HPH through regulation of PINK1-mediated mitophagy signaling. Therefore, PINK1 is a novel therapeutic target for the control of HPH.
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