Steroidogenic acute regulatory protein/aldosterone synthase mediates angiotensin II-induced cardiac fibrosis and hypertrophy

Autor: Ning-Ping Wang, Feng Bai, Erskine A. James, Katelyn Sturdivant, Wei-Wei Zhang, Rong-Hua Zheng, Himangshu S. Bose, Zhi-Qing Zhao
Rok vydání: 2019
Předmět:
0301 basic medicine
Aldosterone synthase
Male
Cardiac fibrosis
Biopsy
Smad2 Protein
chemistry.chemical_compound
0302 clinical medicine
Adrenal Glands
Myofibroblasts
Aldosterone
biology
Steroidogenic acute regulatory protein
Aldosterone Receptor Antagonist
Angiotensin II
General Medicine
Immunohistochemistry
030220 oncology & carcinogenesis
cardiovascular system
Collagen
Disease Susceptibility
Cardiomyopathies
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Signal Transduction
medicine.medical_specialty
Cardiomegaly
Models
Biological
Receptor
Angiotensin
Type 1
03 medical and health sciences
Internal medicine
Genetics
medicine
Animals
Cytochrome P-450 CYP11B2
Smad3 Protein
Molecular Biology
Angiotensin II receptor type 1
Macrophages
Myocardium
medicine.disease
Phosphoproteins
Fibrosis
Rats
Disease Models
Animal
030104 developmental biology
Endocrinology
chemistry
biology.protein
Telmisartan
Biomarkers
Zdroj: Molecular biology reports. 47(2)
ISSN: 1573-4978
Popis: Aldosterone produced in adrenal glands by angiotensin II (Ang II) is known to elicit myocardial fibrosis and hypertrophy. This study was designed to test the hypothesis that Ang II causes cardiac morphological changes through the steroidogenic acute regulatory protein (StAR)/aldosterone synthase (AS)-dependent aldosterone synthesis primarily initiated in the heart. Sprague-Dawley rats were randomized to following groups: Ang II infusion for a 4-week period, treatment with telmisartan, spironolactone or adrenalectomy during Ang II infusion. Sham-operated rats served as control. Relative to Sham rats, Ang II infusion significantly increased the protein levels of AT1 receptor, StAR, AS and their tissue expression in the adrenal glands and heart. In coincidence with reduced aldosterone level in the heart, telmisartan, an AT1 receptor blocker, significantly down-regulated the protein level and expression of StAR and AS. Ang II induced changes in the expression of AT1/StAR/AS were not altered by an aldosterone receptor antagonist spironolactone. Furthermore, Ang II augmented migration of macrophages, protein level of TGFβ1, phosphorylation of Smad2/3 and proliferation of myofibroblasts, accompanied by enhanced perivascular/interstitial collagen deposition and cardiomyocyte hypertrophy, which all were significantly abrogated by telmisartan or spironolactone. However, adrenalectomy did not fully suppress Ang II-induced cell migration/proliferation and fibrosis/hypertrophy, indicating a role of aldosterone synthesized within the heart in pathogenesis of Ang II induced injury. These results indicate that myocardial fibrosis and hypertrophy stimulated by Ang II is associated with tissue-specific activation of aldosterone synthesis, primarily mediated by AT1/StAR/AS signaling pathways.
Databáze: OpenAIRE
Externí odkaz: