Vascular Induction of a Disintegrin and Metalloprotease 17 by Angiotensin II Through Hypoxia Inducible Factor 1α
| Autor: | Tomonori Kobayashi, Takashi Obama, Martine Charbonneau, Katherine J. Elliott, Allison M. Bourne, Takehiko Takayanagi, Satoru Eguchi, Claire M. Dubois |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Myocytes Smooth Muscle ADAM17 Protein Brief Communication Muscle Smooth Vascular Rats Sprague-Dawley Internal medicine Renin–angiotensin system Internal Medicine medicine Disintegrin Animals RNA Messenger Promoter Regions Genetic Cells Cultured Metalloproteinase biology business.industry Angiotensin II Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit ADAM Proteins Up-Regulation Mice Inbred C57BL Endocrinology Hypoxia-inducible factors Cancer research biology.protein medicine.symptom business Signal Transduction |
| Popis: | A disintegrin and metalloprotease 17 (ADAM17) is a membrane-spanning metalloprotease overexpressed in various cardiovascular diseases such as hypertension and atherosclerosis. However, little is known regarding the regulation of ADAM17 expression in the cardiovascular system. Here, we test our hypothesis that angiotensin II induces ADAM17 expression in the vasculature.Cultured vascular smooth muscle cells were stimulated with 100 nM angiotensin II. Mice were infused with 1 μg/kg/minute angiotensin II for 2 weeks. ADAM17 expression was evaluated by a promoter-reporter construct, quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry.In vascular smooth muscle cells, angiotensin II increased ADAM17 protein expression, mRNA, and promoter activity. We determined that the angiotensin II response involves hypoxia inducible factor 1α and a hypoxia responsive element. In angiotensin II-infused mice, marked induction of ADAM17 and hypoxia inducible factor 1α was seen in vasculatures in heart and kidney, as well as in aortae, by immunohistochemistry.Angiotensin II induces ADAM17 expression in the vasculatures through a hypoxia inducible factor 1α-dependent transcriptional upregulation, potentially contributing to end-organ damage in the cardiovascular system. |
| Databáze: | OpenAIRE |
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