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Oxygen regulation of arterial smooth muscle cell proliferation and survival.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ray, Julie Basu Arab, Sara Deng, Yupu Liu, Peter J. Penn, Linda Courtman, David W. Ward, Michael E. |
| Copyright Year | 2008 |
| Abstract | 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% O(2), proliferation and progression through the G1/S interphase are enhanced. Incubation at 1% O(2) 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% O(2), 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-alpha (HIF-1alpha) are increased to a similar extent in HASMCs incubated at 1 and 3% O(2), 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. |
| Starting Page | 9 |
| Ending Page | 9 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpheart.physiology.org/content/ajpheart/294/2/H839.full.pdf |
| Alternate Webpage(s) | http://ajpheart.physiology.org/content/ajpheart/294/2/h839.full.pdf |
| Alternate Webpage(s) | http://ajpheart.physiology.org/content/early/2007/11/30/ajpheart.00587.2007.full.pdf |
| PubMed reference number | 18055518v1 |
| Volume Number | 294 |
| Issue Number | 2 |
| Journal | American journal of physiology. Heart and circulatory physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenosine Triphosphate Aorta Apoptosis Cell Death Cessation of life Gene Expression Profiling HIF1alpha protein Hypoxia Interphase Leukemia, B-Cell Mesenteric Arteries Mesentery Metabolic Process, Cellular Mitochondrial Membranes Muscle Cells Mutation Myocytes, Smooth Muscle Neoplasms Oxygen Protein p53 Smooth muscle (tissue) TP53 gene Transcription, Genetic Vascular Remodeling Vasculature incubated membrane depolarization mitochondrial depolarization muscle cell proliferation |
| Content Type | Text |
| Resource Type | Article |