Abstract

Women experience a dramatical raise in cardiovascular events after menopause. The decline in estrogens is pointed to as the major responsible trigger for the increased risk of cardiovascular disease (CVD). Indeed, the menopausal transition associates with heart macro-remodeling, which results from a fine-tuned cell micro-remodeling. The remodeling of cardiomyocytes is a biomolecular response to several physiologic and pathologic stimuli, allowing healthy adaptation in normal conditions or maladaptation in an unfavorable environment, ending in organ architecture disarray. Estrogens largely impinge on cardiomyocyte remodeling, but they cannot fully explain the sex-dimorphism of CVD risk. Albeit cell remodeling and adaptation are under multifactorial regulation, vitamin D emerges to exert significant protective effects, controlling some intracellular paths, often shared with estrogen signaling. In post-menopause, the unfavorable association of hypoestrogenism-D hypovitaminosis may converge towards maladaptive remodeling and contribute to increased CVD risk. The aim of this review is to overview the role of estrogens and vitamin D in female cardiac health, speculating on their potential synergistic effect in cardiomyocyte remodeling, an issue that is not yet fully explored. Further learning the crosstalk between these two steroids in the biomolecular orchestration of cardiac cell fate during adaptation may help the translational approach to future cardioprotective strategies for women health.

Highlights

  • This review aims to offer first an overview on the role of estrogens and vitamin D in cardiovascular female health, focusing on cardiomyocyte remodeling

  • Sex undeniably matters in cardiac health, vitamin D tightly affects heart function in females and males

  • Cardiomyocyte remodeling, the cellular event driving whole organ macro-remodeling is recognized to be sex-dimorphic and affected by vitamin D. Supplementation with both hormones apparently would offer a promising approach in women cardiovascular diseases (CVD) prevention, especially in post-menopause life

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The midlife estrogen withdrawal is recognized as being the main traditional cause of CVD increase and heart failure (HF) in post-menopausal women [3]. The menopausal transition associates with adverse organ macro-remodeling, which is in turn ascribable to cardiac and endothelial cell micro-remodeling (which occurs in a sex-specific mode [4,5]). Those effects largely depend on the presence of estrogen receptors (ER) within the myocardium and endothelium, and encompass many cellular biological functions by genomic and non-genomic mechanisms [6–8]. As for estrogens, whereas vitamin D actions onto vascular cells are quite exhaustively covered in literature, its molecular effect onto cardiomyocytes is still incompletely understood, especially from sex-dependent standpoint. Brief comments on the impact of possible protective interventions, such as a combined supplementation of these hormones or physical activity are mentioned in the conclusive part

Cardiovascular Health: A Sex Hormone Matter
Estrogens and Cardiomyocyte Remodeling
Estrogen Receptors
Sex-Dimorphic Mitochondrial Function
Cardiovascular Health beyond Sex Hormones
Vitamin D and Cardiomyocyte Remodeling
Vitamin and Estrogen
Conclusions
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