Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy
Name:
journal.pone.0189315.pdf
Size:
4.816Mb
Format:
PDF
Description:
Final Published Version
Author
Tripathi, RanjanaSullivan, Ryan
Fan, Tai-Hwang M.
Wang, Dong
Sun, Yao
Reed, Guy L.
Gladysheva, Inna P.

Affiliation
Univ Arizona, Dept Med, Coll Med PhoenixIssue Date
2017-12-14
Metadata
Show full item recordPublisher
PUBLIC LIBRARY SCIENCECitation
Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy 2017, 12 (12):e0189315 PLOS ONEJournal
PLOS ONERights
© 2017 Tripathi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Dilated cardiomyopathy (DCM) is the major cause of heart failure affecting both women and men. Limited clinical studies show conflicting data in sex-related differences in the progression of dilated cardiomyopathy and heart failure (HF) outcomes. We examined the comparative sex-related progression of cardiomyopathy and the development of HF (at 4, 7, 13 weeks of age) in a well-established, transgenic mouse model of DCM that recapitulates the progressive stages of human HF. By 13 weeks of age, female mice with DCM had more severe left ventricular systolic dysfunction, left ventricular dilation and wall thinning (P< 0.001 for all) than age-matched male mice with DCM. Female mice also had greater lung edema (P< 0.001), cardiac fibrosis (P< 0.01) and pleural effusions, which were not rescued by ovariectomy. By comparison to DCM male mice at 13 weeks, these pathological changes in female mice with DCM, were associated with significant increases in plasma active renin (P< 0.01), angiotensin II (P< 0.01) and aldosterone levels (P< 0.001). In comparison to DCM male mice, DCM female mice also showed differential expression of the natriuretic peptide system with lower corin and higher ANP, BNP and cGMP levels at 13 weeks of age. We conclude, that female mice with experimental DCM have an accelerated progression of cardiomyopathy and HF, which was not corrected by early ovariectomy. These alterations are associated with early renin activation with increased angiotensin II and aldosterone levels, and altered expression of the natriuretic peptide system.Note
Open access journal.ISSN
1932-6203Version
Final published versionSponsors
NIH [HL092750, NS089707, HL115036]; Scientist Development Grant from AHA [14SDG20510068]Additional Links
http://dx.plos.org/10.1371/journal.pone.0189315ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0189315