Journal of the American Heart Association
September 24, 2026 · via Europe PMC
Ovariectomy and Chemical Ovarian Failure Exacerbate Atherosclerosis Without Impairing Recovery From Hindlimb Ischemia.
Buck MY, Pass CG, Choi J, Moparthy D, Law NH, Ryan TE.
AI summary — for doctors, generated from the abstract only
In a mouse study, both surgical and chemical induction of menopause-like ovarian failure significantly worsened plaque buildup in arteries, even though cholesterol levels and body weight remained unchanged, supporting the importance of including menopause models in preclinical heart disease research.
What was studied
A laboratory study in female mice with a genetically induced high-cholesterol condition, comparing atherosclerosis development and recovery from induced leg artery blockage (hindlimb ischemia) between normally cycling control mice, mice with chemically induced ovarian failure, and mice with surgically removed ovaries (ovariectomy).
Key findings
- Both chemical ovarian failure and ovariectomy reduced uterus mass (confirming ovarian failure) without affecting body weight, body composition, or circulating cholesterol levels compared with control mice.
- Despite similar metabolic and cholesterol profiles, atherosclerotic plaque areas were 1.5 to 1.7 times greater in both ovarian failure and ovariectomy mice compared with control mice.
- Recovery of blood flow and muscle function after induced leg artery blockage was similar across all groups, though muscle oxygenation was reduced in both ovarian failure and ovariectomy groups.
Clinical relevance
These findings support the biological plausibility of menopause as an independent driver of increased atherosclerosis risk in women, separate from changes in cholesterol or body weight, and suggest that future preclinical cardiovascular disease research should incorporate menopause models to improve how well animal study findings translate to real-world outcomes in women.
Who should care
Limitations
This is a basic laboratory animal study, so findings require confirmation in human studies before direct clinical application; the specific mechanisms linking ovarian failure to increased atherosclerosis independent of cholesterol changes were not fully elucidated in this study.
In a mouse study, both surgical and chemically induced menopause significantly worsened artery plaque buildup without changing cholesterol levels, supporting the idea that menopause itself, not just its metabolic side effects, directly drives increased heart disease risk in women.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
Peripheral artery disease is a major manifestation of atherosclerotic cardiovascular disease (ASCVD) that affects both men and women. In women, menopause increases the ASCVD risk. However, preclinical ASCVD research has historically been conducted predominantly in men, with relatively few studies focused on women and even fewer incorporating menopause models that more closely reflect human ASCVD pathobiology. Herein, we tested whether the chemical 4-vinylcyclohexene diepoxide (4-VCD)-induced ovarian failure or ovariectomy would drive atherosclerotic development and worsen ischemic limb pathophysiology.
Methods
Female C57BL/6J mice were injected with adeno-associated virus-mediated encoding a gain-of-function mutant PCSK9 (proprotein convertase subtilisin/kexin type 9) and fed an atherogenic diet for 23 weeks. Based on the baseline body weight, mice were randomly assigned to normally cycling controls, 4-VCD, or ovariectomy groups. Three weeks after the conformation of ovarian failure (4-VCD) or surgical ovarian removal (ovariectomy), hindlimb ischemia was induced via femoral artery ligation, and limb perfusion recovery and limb muscle performance were assessed.
Results
Both 4-VCD treatment and ovariectomy reduced uterus mass, without affecting body weight or composition, or circulating cholesterol levels compared with control mice. Despite the similar metabolic and cholesterol profiles, atherosclerotic lesion areas were 1.5 to 1.7-fold greater in 4-VCD and ovariectomy mice than control mice. Perfusion recovery following hindlimb ischemia and plantar flexor muscle function in the ischemic limb were similar across groups, though muscle oxygenation was reduced in 4-VCD and ovariectomy groups.
Conclusions
Ovarian failure and removal exacerbated atherosclerotic development but had minimal impacts on perfusion recovery and limb function following hindlimb ischemia. These findings confirm the inclusion of menopausal models, whether through ovarian failure or ovariectomy, should be carefully considered to improve translatability of preclinical ASCVD studies, especially for women's health.
DOI
10.1161/jaha.126.053158
PMID
42786647
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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