A Defective Extracellular Matrix/Kindlin-2/Actin/ERK Mechanosensing Pathway Affects Fibroblast-To-Myofibroblast Transition in the Old Male Heart

Heart failure represents a leading cause of mortality in the elderly population. Although aging features include diastolic dysfunction and interstitial fibrosis in both males and females, it becomes increasingly apparent that aged male and female hearts are phenotypically different. There were fundamental differences in extracellular matrix (ECM) composition and architecture and heart function indices at the baseline, which were further accentuated by Aicar treatment. By combining in vivo, ex vivo, and in vitro strategies, we demonstrated that there are sex-specific features that influence the response to pharmacological intervention in the aging mouse heart