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Review
. 2019 Feb 4;10(1):7.
doi: 10.1186/s13293-019-0223-0.

Sex-specific influence on cardiac structural remodeling and therapy in cardiovascular disease

Elise L Kessler  1   2 , Mathilde R Rivaud  3   4 , Marc A Vos  3 , Toon A B van Veen  3
Affiliations
Review

Sex-specific influence on cardiac structural remodeling and therapy in cardiovascular disease

Elise L Kessler et al. Biol Sex Differ. .

Abstract

Background: Cardiovascular diseases (CVDs) culminating into heart failure (HF) are major causes of death in men and women. Prevalence and manifestation, however, differ between sexes, since men mainly present with coronary artery disease (CAD) and myocardial infarction (MI), and post-menopausal women predominantly present with hypertension. These discrepancies are probably influenced by underlying genetic and molecular differences in structural remodeling pathways involved in hypertrophy, inflammation, fibrosis, and apoptosis. In general, men mainly develop eccentric forms, while women develop concentric forms of hypertrophy. Besides that, women show less inflammation, fibrosis, and apoptosis upon HF. This seems to emerge, at least partially, from the fact that the underlying pathways might be modulated by estrogen, which changes after menopause due to declining of the estrogen levels.

Conclusion: In this review, sex-dependent alterations in adverse cardiac remodeling are discussed for various CVDs. Moreover, potential therapeutic options, like estrogen treatment, are reviewed.

Keywords: Apoptosis; Cardiovascular disease; Fibrosis; Hypertrophy; Inflammation; Sex.

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The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Generalized development of sex differences in structural cardiac remodeling and possible heart failure (HF) outcomes. Men (blue lines) and women (red lines) often show different structural remodeling after an initial injury (e.g., hypertension and MI.) leading to acute inflammation and different disease outcomes. In general, women tend to develop HF later than men. The older, the more patients suffer from cardiovascular diseases; however, in women this seems to be clearly related to the onset of their menopause. Thickness of lines mirrors the general number of patients suffering from the HF type at that age
Fig. 2
Fig. 2
Molecular signaling of inflammatory pathways involved in structural remodeling. Inflammatory pathways activated upon cardiac injury include the IFN-γ/JAK-STAT pathway (purple), the TLR pathway (green; either in an endosome (left pathway) or on the cell membrane (right pathway)), the TNF-α/MEKK pathway (red), and the TGF-β/BMP/SMAD pathway (blue), triggering secretion of cytokines and chemokines and leading to, e.g., apoptosis and cell proliferation. Crosstalk between the pathways is possible (dashed arrow) and collaboration with the Wnt pathway (light gray) and CaMKII (dark gray) promoting cardiac inflammation. Sex differences in these pathways are discussed in the text, such as the inhibitory effects of estrogen on CaMKII, BNP, and NFκB
See this image and copyright information in PMC

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