ArticleCirculation research2004
Human cytomegalovirus causes endothelial injury through the ataxia telangiectasia mutant and p53 DNA damage signaling pathways.
Article in Circulation research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages.Science advances · 2026Article
- Human cytomegalovirus UL78 is a nuclear-localized GPCR necessary for efficient reactivation from latent infection in CD34Journal of virology · 2025Article
- Molecular mechanisms of HCMV-driven vascular remodeling and its significance in cardiovascular diseases.Archives of microbiology · 2025Review
- The Interplay Between Immunity, Inflammation and Endothelial Dysfunction.International journal of molecular sciences · 2025Review
- Review
- DNA damage response(DDR): a link between cellular senescence and human cytomegalovirus.Virology journal · 2023Review
- Cordycepin Induces Apoptosis through JNK-Mediated Caspase Activation in Human OEC-M1 Oral Cancer Cells.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Vitamin D3 Suppresses Human Cytomegalovirus-Induced Vascular Endothelial ApoptosisFrontiers in microbiology · 2022Article
- Role of JNK activation in paclitaxel-induced apoptosis in human head and neck squamous cell carcinoma.Oncology letters · 2021Article
- Apoptosis Disorder, a Key Pathogenesis of HCMV-Related Diseases.International journal of molecular sciences · 2021Review
- Infection of a Single Cell Line with Distinct Strains of Human Cytomegalovirus Can Result in Large Variations in Virion Production and Facilitate Efficient Screening of Virus Protein Function.Journal of virology · 2015Article
- Protective roles of Gadd45 and MDM2 in blueberry anthocyanins mediated DNA repair of fragmented and non-fragmented DNA damage in UV-irradiated HepG2 cells.International journal of molecular sciences · 2013Article
- Live or let die: manipulation of cellular suicide programs by murine cytomegalovirus.Medical microbiology and immunology · 2012Review
- RNA interference-mediated targeting of human cytomegalovirus immediate-early or early gene products inhibits viral replication with differential effects on cellular functions.Journal of virology · 2012Article
- Expression of the RAE-1 family of stimulatory NK-cell ligands requires activation of the PI3K pathway during viral infection and transformation.PLoS pathogens · 2011Article
- PKCζ mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation.The Journal of cell biology · 2011Article
- An E2F1-mediated DNA damage response contributes to the replication of human cytomegalovirus.PLoS pathogens · 2011Article
- Socioeconomic disparities in the seroprevalence of cytomegalovirus infection in the US population: NHANES III.Epidemiology and infection · 2009Article
- Biomarkers related to aging in human populations.Advances in clinical chemistry · 2008Review
- HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia.BMC microbiology · 2007Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Atherosclerosis is the leading cause of death in the United States, and human cytomegalovirus (HCMV), a member of the herpes virus family, may play a role in the development of the disease. We previously showed that HCMV regulated endothelial apoptosis. In this study, we investigated the induction of apoptosis and signal transduction pathways regulating this process in HCMV-infected endothelial cells. As observed previously, HCMV induced a typical cytopathic effect in human aortic endothelial cells (HAECs), ie, the formation of single nucleated or multinucleated giant cells. Although infected HAECs were resistant to apoptosis at earlier stages of infection, they became apoptotic with prolonged infection as demonstrated by positive staining using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). This apoptotic process was mediated by the caspase-dependent mitochondrial apoptotic pathway as indicated by increased expression and cleavage of caspases 3 and 9 as well as increased expressions of pro-apoptotic molecules Bax and Bak. Blocking caspases 3 or 9 significantly inhibited the HCMV-induced apoptosis. Further exploration of the upstream pathway demonstrated upregulation of the tumor suppressor p53 gene and activation of the ataxia telangiectasia mutant (ATM) pathway in the infected cells. Blocking p53 inhibited HCMV-stimulated Bax and Bak expression as well as caspase-3 activation and blocking the ATM pathway inhibited HCMV-stimulated p53 activation. Although early infection may render cells antiapoptotic, prolonged infection, however, induced endothelial apoptosis through ATM and p53-dependent activation of the mitochondrial death pathway. This proapoptotic effect may be relevant to endothelial dysfunction and HCMV-associated vascular diseases.
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Registered trials
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