Abstract
Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. However, while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. Then, we discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis.
Highlights
Despite recent advances in medical and interventional therapies, cardiovascular disease (CVD) remains a leading global cause of death in men and women
That HF with preserved ejection fraction (HFpEF) is associated with female sex independent of obesity and diabetes (Lee et al, 2009; Dunlay et al, 2017), it is reasonable to assume that estrogen decline and subsequent cyclic guanosine monophosphate (cGMP) deactivation may contribute to the pathophysiology of HFpEF
Using a novel knock-in mice, whose ERα are replaced with the ERα harboring triple-point KRR mutation, we recently reported that rapid non-nuclear ERα signaling is indispensable for estrogen to provide nitric oxide (NO) that activates soluble guanylate cyclase (sGC) (Figure 1; Fukuma et al, 2020)
Summary
Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. We discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis
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