4.6 Article

Using 4-vinylcyclohexene diepoxide as a model of menopause for cardiovascular disease

Journal

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00555.2019

Keywords

4-vinylcyclohexene diepoxide; angiotensin II; cardiac injury; hypertension; menopause

Funding

  1. National Institutes of Health [R01-HL098256, K01-AR052840, K02-HL-105799]
  2. American Heart Association [16GRNT31390006]
  3. Computational and Mathematical Modeling of Biomedical Systems Interdisciplinary Training Grant [GM-004905]
  4. Cardiovascular Sciences Interdisciplinary Training Grants [HL-007249, HL-00795515]
  5. Sarver Heart Center at the University of Arizona
  6. Steven M. Gootter Foundation

Ask authors/readers for more resources

There is a sharp rise in cardiovascular disease (CVD) risk and progression with the onset of menopause. The 4-vinylcyclohexene diepoxide (VCD) model of menopause recapitulates the natural, physiological transition through perimenopause to menopause. We hypothesized that menopausal female mice were more susceptible to CVD than pre- or perimenopausal females. Female mice were treated with VCD or vehicle for 20 consecutive days. Premenopausal, perimenopausal, and menopausal mice were administered angiotensin II (ANG II) or subjected to ischemia-reperfusion (I/R). Menopausal females were more susceptible to pathological ANG II-induced cardiac remodeling and cardiac injury from a myocardial infarction (MI), while perimenopausal, like premenopausal, females remained protected. Specifically, ANG II significantly elevated diastolic (130.9 +/- 6.0 vs. 114.7 +/- 6.2 mmHg) and systolic (156.9 +/- 4.8 vs. 141.7 +/- 5.0 mmHg) blood pressure and normalized cardiac mass (15.9 +/- 1.0 vs. 7.7 +/- 1.5%) to a greater extent in menopausal females compared with controls, whereas perimenopausal females demonstrated a similar elevation of diastolic (93.7 +/- 2.9 vs. 100.5 +/- 4.1 mmHg) and systolic (155.9 +/- 7.3 vs. 152.3 +/- 6.5 mmHg) blood pressure and normalized cardiac mass (8.3 +/- 2.1 vs. 7.5 +/- 1.4%) compared with controls. Similarly, menopausal females demonstrated a threefold increase in fibrosis measured by Picrosirus red staining. Finally, hearts of menopausal females (41 +/- 5%) showed larger infarct sizes following I/R injury than perimenopausal (18.0 +/- 5.6%) and premenopausal (16.2 +/- 3.3, 20.1 +/- 4.8%) groups. Using the VCD model of menopause, we provide evidence that menopausal females were more susceptible to pathological cardiac remodeling. We suggest that the VCD model of menopause may be critical to better elucidate cellular and molecular mechanisms underlying the transition to CVD susceptibility in menopausal women. NEW & NOTEWORTHY Before menopause, women are protected against cardiovascular disease (CVD) compared with age-matched men; this protection is gradually lost after menopause. We present the first evidence that demonstrates menopausal females are more susceptible to pathological cardiac remodeling while perimenopausal and cycling females are not. The VCD model permits appropriate examination of how increased susceptibility to the pathological process of cardiac remodeling accelerates from pre- to perimenopause to menopause.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available