The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease

Abstract

Nearly one-third of deaths in the United States are caused by cardiovascular disease (CVD) each year. In the past, CVD was thought to mainly affect men leading to the exclusion of women and female animals from clinical studies and preclinical research. In light of sexual dimorphisms in CVD, a need exists to examine baseline cardiac differences in humans and the animals used to model CVD. In humans, sex differences are apparent at every level of cardiovascular physiology from action potential duration and mitochondrial energetics to cardiac myocyte and whole heart contractile function. Biological sex is an important modifier of the development of CVD with younger women generally being protected, but this cardioprotection is lost later in life, suggesting a role for estrogen. While endogenous estrogen is most likely a mediator of the observed functional differences in both health and disease, the signaling mechanisms involved are complex and are not yet fully understood. To investigate how sex modulates CVD development, animal models are essential tools and should be useful in the development of therapeutics. This review will focus on describing the cardiovascular sexual dimorphisms that exist both physiologically as well as in common animal models of CVD.

Ergosterol Attenuates LPS-Induced Myocardial Injury by Modulating Oxidative Stress and Apoptosis in Rats

“…Thus, LPS-induced endotoxemia cardiac injury model was used in this study. We also limited our animal model to male rats to avoid the effects of estrogen, which has been shown to protect against ischemic injury and inhibit arteriosclerosis and myocardial hypertrophy [20,21]. This in vivo model has been successfully validated as shown by alterations in the sarcolemmal integrity of myocardial cells during histological examinations and serum elevations of CK-MB and LDH enzymes.…”

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

“…Additionally, for practical reasons, all experiments were performed only in male mice, and there is evidence that HF differentially impacts male and females (Blenck et al. 2016), and that estrogen can modulate the transcriptional activity of MR (Barrett Mueller et al. 2014).…”

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

“…However, the importance of studying the response of both male and female hearts is becoming clear, as sex can clearly influence sensitivity to ischemia [47, 323]. …”