Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats

Autor: Carlos M. Ferrario, Sarfaraz Ahmad, Jaqueline da Silva, Marina Lin, Mark C. Chappell, Jewell A. Jessup, Zhuo Zhao, Leanne Groban, Lindsay M. MacNamara, Hao Wang
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Angiotensinogen
Gene Expression
lcsh:Medicine
030204 cardiovascular system & hematology
Proto-Oncogene Mas
Receptors
G-Protein-Coupled
Renin-Angiotensin System
chemistry.chemical_compound
Mice
Random Allocation
0302 clinical medicine
Gene expression
Renin
Mast Cells
Receptor
lcsh:Science
0303 health sciences
Multidisciplinary
Aldosterone
Estradiol
Chemistry
Reverse Transcriptase Polymerase Chain Reaction
Mast cell
Immunohistochemistry
medicine.anatomical_structure
Matrix Metalloproteinase 9
Female
Rats
Transgenic
hormones
hormone substitutes
and hormone antagonists
Research Article
medicine.medical_specialty
medicine.drug_class
Ovariectomy
Blotting
Western
Receptor
Angiotensin
Type 1
03 medical and health sciences
Chymases
Internal medicine
Proto-Oncogene Proteins
Renin–angiotensin system
medicine
Animals
030304 developmental biology
Myocardium
lcsh:R
Chymase
Estrogens
medicine.disease
Peptide Fragments
Rats
Endocrinology
Estrogen
Rats
Inbred Lew
Heart failure
lcsh:Q
Angiotensin I
Zdroj: PLoS ONE, Vol 8, Iss 10, p e76992 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS) is involved in the development and progression of cardiac hypertrophy, remodeling, and heart failure. Estrogen attenuates the effects of an activated circulating RAS; however, its role in regulating the cardiac RAS is unclear. Bilateral oophorectomy (OVX; n = 17) or sham-operation (Sham; n = 13) was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, the rats were randomized and received either 17 β-estradiol (E2, 36 µg/pellet, 60-day release, n = 8) or vehicle (OVX-V, n = 9) for 4 weeks. The rats were sacrificed, and blood and hearts were used to determine protein and/or gene expression of circulating and tissue RAS components. E2 treatment minimized the rise in circulating angiotensin (Ang) II and aldosterone produced by loss of ovarian estrogens. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1-7) content, chymase gene expression, and mast cell number. Neither OVX nor OVX+E2 altered cardiac expression or activity of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R). E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1-7) mas receptor, in comparison to sham-operated and OVX littermates. E2 treatment appears to inhibit upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly by reducing chymase-dependent Ang II formation. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats.
Databáze: OpenAIRE
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