Differential Gender-Dependent Patterns of Cardiac Fibrosis and Fibroblast Phenotypes in Aging Mice

Angela Achkar,Nassim Fares,Youakim Saliba

doi:10.1155/2020/8282157

Angela Achkar, Nassim Fares + Show 1 more

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https://doi.org/10.1155/2020/8282157

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Abstract

Aging is characterized by physiological changes within the heart leading to fibrosis and dysfunction even in individuals without underlying pathologies. Gender has been shown to influence the characteristics of cardiac aging; however, gender-dependent cardiac fibrosis occurring with age remains largely not elucidated. Thus, broadening our understanding of this phenomenon proves necessary in order to develop novel anti-fibrotic strategies in the elderly. In this study, we aim to characterize cardiac fibrosis and cardiac fibroblast (CF) populations in aged male and female mice. Echocardiography revealed eccentric hypertrophy with left ventricular dilatation in the aged male versus concentric hypertrophy with left posterior wall thickening in the female, with preserved cardiac function in both groups. Reactive fibrosis was evidenced in the myocardium and epicardium of the aged female mice hearts whereas perivascular and replacement ones where present in the male heart. Collagen I was predominant in the aged male heart whereas collagen III was the main component in the female heart. CFs in the aged male heart were mainly recruited from resident PDGFRα+ populations but not derived from epicardium as evidenced by the absence of epicardial progenitor transcription factors Tcf21, Tbx18 and Wt1. Our results present a paradigm for gender-dependent cardiac fibrosis and the origins of CFs with age. This sets forth to revisit cardiac anti-fibrotic management according to the gender in the elderly and to explore novel therapeutic targets.

Highlights

Aging is an important risk factor for cardiovascular-related morbidity and mortality
Aged heart exhibits myocardial remodelling that includes among others increased apoptosis and oxidative stress, hemodynamic changes, cardiomyocyte senescence and collagen deposition leading to cardiac fibrosis [1, 2]
Fibrotic tissue is stiffer and less compliant [8], resulting in subsequent cardiac dysfunction and heart failure but with normal or nearly normal ejection fraction. This is known as heart failure with preserved ejection fraction (HFpEF), the most common type of heart failure in the elderly [1, 2, 9]

Summary

Introduction

Aging is an important risk factor for cardiovascular-related morbidity and mortality. Fibrotic tissue is stiffer and less compliant [8], resulting in subsequent cardiac dysfunction and heart failure but with normal or nearly normal ejection fraction. This is known as heart failure with preserved ejection fraction (HFpEF), the most common type of heart failure in the elderly [1, 2, 9]. Clinically and in experimental models to influence the characteristics of cardiac remodelling in disease. This was associated in men with greater expression of fibrotic markers such as collagen genes that further contribute to cardiac dysfunction [10, 11]. There is no direct evidence whether age-related cardiac fibrosis is differential between the male and female

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