Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy

Ranjana Tripathi, Ryan Sullivan, Tai-Hwang Fan, Dong Wang, Yao Sun, Guy L. Reed, Inna P. Gladysheva

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0189315
JournalPloS one
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

renin
cardiomyopathy
Dilated Cardiomyopathy
heart failure
Renin
Heart Failure
Chemical activation
Mortality
mice
Natriuretic Peptides
Aldosterone
Angiotensin II
fibrosis
Fibrosis
natriuretic peptides
Atrial Natriuretic Factor
Ovariectomy
aldosterone
Cardiomyopathies
ovariectomy

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy. / Tripathi, Ranjana; Sullivan, Ryan; Fan, Tai-Hwang; Wang, Dong; Sun, Yao; Reed, Guy L.; Gladysheva, Inna P.

In: PloS one, Vol. 12, No. 12, e0189315, 01.12.2017.

Research output: Contribution to journalArticle

Tripathi, Ranjana ; Sullivan, Ryan ; Fan, Tai-Hwang ; Wang, Dong ; Sun, Yao ; Reed, Guy L. ; Gladysheva, Inna P. / Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy. In: PloS one. 2017 ; Vol. 12, No. 12.
@article{0566597585674148a5286882ae67a74e,
title = "Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy",
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.",
author = "Ranjana Tripathi and Ryan Sullivan and Tai-Hwang Fan and Dong Wang and Yao Sun and Reed, {Guy L.} and Gladysheva, {Inna P.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0189315",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy

AU - Tripathi, Ranjana

AU - Sullivan, Ryan

AU - Fan, Tai-Hwang

AU - Wang, Dong

AU - Sun, Yao

AU - Reed, Guy L.

AU - Gladysheva, Inna P.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85038633255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038633255&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0189315

DO - 10.1371/journal.pone.0189315

M3 - Article

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0189315

ER -