Aldosterone Enhances Ischemia-Induced Neovascularization Through Angiotensin II–Dependent Pathway
| Autor: | Jean-Sébastien Silvestre, Marie-Lory Ambroisine, Claude Delcayre, Bernard I. Levy, Micheline Duriez, Frédéric Michel |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty medicine.drug_class Neovascularization Physiologic Renin-Angiotensin System Neovascularization Mice chemistry.chemical_compound Mineralocorticoid receptor Ischemia Physiology (medical) Internal medicine Renin–angiotensin system Animals Medicine RNA Messenger Aldosterone Skin Angiotensin II receptor type 1 business.industry Angiotensin II Mice Inbred C57BL Radiography Endocrinology Valsartan chemistry Regional Blood Flow Mineralocorticoid Blood Vessels Angiogenesis Inducing Agents medicine.symptom Cardiology and Cardiovascular Medicine business Signal Transduction medicine.drug |
| Zdroj: | Circulation. 109:1933-1937 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000127112.36796.9b |
| Popis: | Background— We analyzed the role of aldosterone in ischemia-induced neovascularization and the involvement of angiotensin II (Ang II) signaling in this effect. Methods and Results— Ischemia was induced by right femoral artery ligature in mice treated or not with aldosterone (4.5 μg/day), aldosterone plus spironolactone (aldosterone receptor blocker; 20 mg/kg per day), or aldosterone plus valsartan (angiotensin type 1 [AT 1 ] receptor blocker; 20 mg/kg per day). After 21 days, neovascularization was evaluated by microangiography, capillary density measurement, and laser-Doppler perfusion imaging. Protein level of vascular endothelial growth factor (VEGF) was determined by Western blot analysis in hindlimbs. mRNA levels of renin–angiotensin system components were also assessed by semiquantitative reverse transcription–polymerase chain reaction. Angiographic score, capillary number, and foot perfusion were improved in ischemic/nonischemic leg ratio by 1.4-, 1.5-, and 1.4-fold, respectively, in aldosterone-treated mice compared with controls ( P P P 1 receptor blockade completely abrogated the aldosterone proangiogenic effect, emphasizing the involvement of Ang II–related pathway in aldosterone-induced vessel growth. In this view, angiotensinogen mRNA content was 2.2-fold increased in aldosterone-treated mice in reference to controls ( P 1 receptor subtype was unaffected. Aldosterone treatment also decreased AT 2 mRNA content by 2-fold ( P Conclusions— This study shows for the first time that aldosterone increases neovascularization in the setting of ischemia through activation of Ang II signaling. |
| Databáze: | OpenAIRE |
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