Oxygen regulation of arterial smooth muscle cell proliferation and survival
| Autor: | Michael E. Ward, Peter Liu, David W. Courtman, Julie Basu Ray, Linda Z. Penn, Sara Arab, Yupu Deng |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Cell Survival Physiology Blotting Western Myocytes Smooth Muscle Cell Count Biology Muscle Smooth Vascular Membrane Potentials Rats Sprague-Dawley Adenosine Triphosphate Smooth muscle Physiology (medical) In Situ Nick-End Labeling medicine Animals Myocyte Annexin A5 Cells Cultured Cell Proliferation Oligonucleotide Array Sequence Analysis Cell growth Gene Expression Profiling Cell Cycle DNA Hypoxia (medical) Cell cycle Rats Cell biology Oxygen Blot Ki-67 Antigen Apoptosis Caspases Circulatory system Immunology Indicators and Reagents medicine.symptom Cardiology and Cardiovascular Medicine Signal Transduction Thymidine |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 294:H839-H852 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00587.2007 |
| Popis: | The purpose of this study was to determine if hypoxia elicits different proliferative and apoptotic responses in systemic arterial smooth muscle cells incubated under conditions that do or do not result in cellular ATP depletion and whether these effects are relevant to vascular remodeling in vivo. Gene expression profiling was used to identify potential regulatory pathways. In human aortic smooth muscle cells (HASMCs) incubated at 3% O2, proliferation and progression through the G1/S interphase are enhanced. Incubation at 1% O2 reduced proliferation, delayed G1/S transition, increased apoptotic cell death, and is associated with mitochondrial membrane depolarization and reduced cellular ATP levels. In aorta and mesenteric artery from rats exposed to hypoxia (10% O2, 48 h), both proliferation and apoptosis are increased, as are medial nuclear density and smooth muscle cell content. Although nuclear levels of hypoxia-inducible factor 1-α (HIF-1α) are increased to a similar extent in HASMCs incubated at 1 and 3% O2, expression of tumor protein p53, its transcriptional target p21, as well as their regulatory factors and downstream effectors, are differentially affected under these two conditions, suggesting that the bidirectional effects of hypoxia are mediated by this pathway. We conclude that hypoxia induces a state of enhanced cell turnover through increased rates of both smooth muscle cell proliferation and death. This confers the ability to remodel the vasculature in response to changing tissue metabolic needs while avoiding the accumulation of mutations that may lead to malignant transformation or the formation of abnormal vascular structures. |
| Databáze: | OpenAIRE |
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