ArticleArteriosclerosis, thrombosis, and vascular biology2019
Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- E2F1 Drives Endothelial Arterial Programming in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Cellular senescence in adult pulmonary hypertension: current state and future challenges.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Non-Interferon-Dependent Role of STING Signaling in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Sponge-derived alkaloid AP-7 as a sensitizer to cisplatin in the treatment of multidrug-resistant NSCLC via Chk1-dependent mechanisms.Frontiers in pharmacology · 2024Article
- Exploring the pathogenesis of pulmonary vascular disease.Frontiers in medicine · 2024Review
- Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer.Frontiers in oncology · 2024Review
- Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension.Nature communications · 2023Article
- Frataxin deficiency disrupts mitochondrial respiration and pulmonary endothelial cell function.Vascular pharmacology · 2023Article
- DNA damage response signaling: A common link between cancer and cardiovascular diseases.Cancer medicine · 2023Review
- Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis.Frontiers in immunology · 2023Article
- DNA-PKcs participated in hypoxic pulmonary hypertension.Respiratory research · 2022Article
- CHK yourself, before you wreck yourself: targeting the DNA damage response in secondary pulmonary hypertension.Thorax · 2022Article
- CDC2 Is an Important Driver of Vascular Smooth Muscle Cell Proliferation via FOXM1 and PLK1 in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Frataxin deficiency promotes endothelial senescence in pulmonary hypertension.The Journal of clinical investigation · 2021Article
- lnc-Rps4l-encoded peptide RPS4XL regulates RPS6 phosphorylation and inhibits the proliferation of PASMCs caused by hypoxia.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Implication of EZH2 in the Pro-Proliferative and Apoptosis-Resistant Phenotype of Pulmonary Artery Smooth Muscle Cells in PAH: A Transcriptomic and Proteomic Approach.International journal of molecular sciences · 2021Article
- Preclinical Investigation of Trifluoperazine as a Novel Therapeutic Agent for the Treatment of Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Therapeutic Potential of Regorafenib-A Multikinase Inhibitor in Pulmonary Hypertension.International journal of molecular sciences · 2021Article
- Review
- Selected arylsulphonyl pyrazole derivatives as potential Chk1 kinase ligands-computational investigations.Journal of molecular modeling · 2020Article
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
objectivePulmonary arterial hypertension (PAH) is a debilitating disease associated with progressive vascular remodeling of distal pulmonary arteries leading to elevation of pulmonary artery pressure, right ventricular hypertrophy, and death. Although presenting high levels of DNA damage that normally jeopardize their viability, pulmonary artery smooth muscle cells (PASMCs) from patients with PAH exhibit a cancer-like proproliferative and apoptosis-resistant phenotype accounting for vascular lumen obliteration. In cancer cells, overexpression of the serine/threonine-protein kinase CHK1 (checkpoint kinase 1) is exploited to counteract the excess of DNA damage insults they are exposed to. This study aimed to determine whether PAH-PASMCs have developed an orchestrated response mediated by CHK1 to overcome DNA damage, allowing cell survival and proliferation. Approach and Results: We demonstrated that CHK1 expression is markedly increased in isolated PASMCs and distal PAs from patients with PAH compared with controls, as well as in multiple complementary animal models recapitulating the disease, including monocrotaline rats and the simian immunodeficiency virus-infected macaques. Using a pharmacological and molecular loss of function approach, we showed that CHK1 promotes PAH-PASMCs proliferation and resistance to apoptosis. In addition, we found that inhibition of CHK1 induces downregulation of the DNA repair protein RAD 51 and severe DNA damage. In vivo, we provided evidence that pharmacological inhibition of CHK1 significantly reduces vascular remodeling and improves hemodynamic parameters in 2 experimental rat models of PAH.
conclusionsOur results show that CHK1 exerts a proproliferative function in PAH-PASMCs by mitigating DNA damage and suggest that CHK1 inhibition may, therefore, represent an attractive therapeutic option for patients with PAH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.