Sex and Ventricular Remodeling

The composite of changes sustained by the left ventricle during pathologic and physiologic stimuli is known as ventricular remodeling. These changes involve alterations to individual cells, the surrounding matrix, and overall ventricular structure and function. Following myocardial infarction, ventricular remodeling involves partial tissue repair and ultimately determines long-term survival. Biological sex contributes to diverging responses in post-infarction ventricular remodeling and survival, with young female animals having less remodeling post-injury compared with male animals, yet women have reduced long-term survival. Over the last two decades, evidence indicates that sex-dependent differences impact most processes that contribute to post-infarction remodeling, including extracellular matrix remodeling, inflammation, and cardiomyocyte homeostasis. In addition, there are differences in the transcriptional landscape and cellular composition of male and female hearts. Despite these well-established sex-dependent differences, mechanistic advancements lag. Furthermore, cardiovascular treatments are not yet optimized based on sex. Sex hormones are proffered as the explanation for differences; however, studies that remove the influence of sex hormones still show sex-dependent changes, which suggests hormone-independent contributors. Outside of pathological remodeling in response to infarction, the female heart often undergoes physiological remodeling that does not occur in males: pregnancy. During pregnancy, rapid remodeling and reversion occur, which creates a unique, natural template to study aspects of sex-dependent differences in ventricular remodeling. Therefore, this review summarizes fundamental differences in the ventricular myocardium between sexes and highlights emerging areas that contribute to sex-dependent changes in ventricular remodeling.