ArticleAmerican journal of respiratory cell and molecular biology2013
Adenosine monophosphate-activated protein kinase is required for pulmonary artery smooth muscle cell survival and the development of hypoxic pulmonary hypertension.
Article in American journal of respiratory cell and molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- Altitude hypoxia and hypoxemia: pathogenesis and management.Signal transduction and targeted therapy · 2026Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Anti-PCSK9 Treatment Attenuates Liver Fibrosis via Inhibiting Hypoxia-Induced Autophagy in Hepatocytes.Inflammation · 2023Article
- A role of TRIM59 in pulmonary hypertension: modulating the protein ubiquitylation modification.Journal of translational medicine · 2023Article
- Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies.The Journal of clinical investigation · 2023Article
- Skeletal and cardiac muscle have different protein turnover responses in a model of right heart failure.GeroScience · 2023Article
- Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK.American journal of physiology. Heart and circulatory physiology · 2023Article
- AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension.International journal of molecular sciences · 2022Review
- AMPK and Pulmonary Hypertension: Crossroads Between Vasoconstriction and Vascular Remodeling.Frontiers in cell and developmental biology · 2021Review
- Metformin prevents the development of monocrotaline-induced pulmonary hypertension by decreasing serum levels of big endothelin-1.Experimental and therapeutic medicine · 2020Article
- Nitric oxide activates AMPK by modulating PDE3A in human pulmonary artery smooth muscle cells.Physiological reports · 2020Article
- Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.Redox biology · 2020Review
- AMPKα2 deficiency exacerbates hypoxia-induced pulmonary hypertension by promoting pulmonary arterial smooth muscle cell proliferation.Journal of physiology and biochemistry · 2020Article
- Sodium Tanshinone II Sulfonate A Ameliorates Hypoxia-Induced Pulmonary Hypertension.Frontiers in pharmacology · 2020Article
- New Insights Into Heat Shock Protein 90 in the Pathogenesis of Pulmonary Arterial Hypertension.Frontiers in physiology · 2020Review
- Protein expression profile changes of lung tissue in patients with pulmonary hypertension.PeerJ · 2020Article
- Smooth muscle cell-specific FoxM1 controls hypoxia-induced pulmonary hypertension.Cellular signalling · 2018Article
- Alpha-enolase regulates the malignant phenotype of pulmonary artery smooth muscle cells via the AMPK-Akt pathway.Nature communications · 2018Article
- Cell death-inducing DFF45-like effector C gene silencing alleviates pulmonary vascular remodeling in a type 2 diabetic rat model.Journal of diabetes investigation · 2018Article
- Models and Molecular Mechanisms of World Health Organization Group 2 to 4 Pulmonary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Human pulmonary artery smooth muscle cells (HPASMCs) express both adenosine monophosphate-activated protein kinase (AMPK) α1 and α2. We investigated the distinct roles of AMPK α1 and α2 in the survival of HPASMCs during hypoxia and hypoxia-induced pulmonary hypertension (PH). The exposure of HPASMCs to hypoxia (3% O2) increased AMPK activation and phosphorylation, and the inhibition of AMPK with Compound C during hypoxia decreased their viability and increased lactate dehydrogenase activity and apoptosis. Although the suppression of either AMPK α1 or α2 expression led to increased cell death, the suppression of AMPK α2 alone increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. It also resulted in the decreased expression of myeloid cell leukemia sequence 1 (MCL-1). The knockdown of MCL-1 or MCL-1 inhibitors increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. On the other hand, the suppression of AMPK α1 expression alone prevented hypoxia-mediated autophagy. The inhibition of autophagy induced cell death in HPASMCs. Our results suggest that AMPK α1 and AMPK α2 play differential roles in the survival of HPASMCs during hypoxia. The activation of AMPK α2 maintains the expression of MCL-1 and prevents apoptosis, whereas the activation of AMPK α1 stimulates autophagy, promoting HPASMC survival. Moreover, treatment with Compound C, which inhibits both isoforms of AMPK, prevented and partly reversed hypoxia-induced PH in mice. Taking these results together, our study suggests that AMPK plays a key role in the pathogenesis of pulmonary arterial hypertension, and AMPK may represent a novel therapeutic target for the treatment of pulmonary arterial hypertension.
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