Endothelial-cell-mediated mechanism of coronary microvascular dysfunction leading to heart failure with preserved ejection fraction.

Although the prevalence of heart failure with preserved ejection fraction (HFpEF) is growing worldwide, its complex pathophysiology has yet to be fully elucidated, and multiple hypotheses have all failed to produce a viable target for therapeutic action or provide effective treatment. Cardiac remodeling has long been considered an important mechanism of HFpEF. Strong evidence has been reported over the past years that coronary microvascular dysfunction (CMD), manifesting as structural and functional abnormalities of coronary microvasculature, also contributes to the evolution of HFpEF. However, the mechanisms of CMD are still not well understood and need to be studied further. Coronary microvascular endothelial cells (CMECs) are one of the most abundant cell types in the heart by number and active players in cardiac physiology and pathology. CMECs are not only important cellular mediators of cardiac vascularization but also play an important role in disease pathophysiology by participating in the inception and progression of cardiac remodeling. CMECs are also actively involved in the pathogenesis of CMD. Numerous studies have confirmed that CMD is closely related to cardiac remodeling. ECs may serve a critical function in mediating the connection between CMD and HFpEF. It follows that CMECs participate in the mechanism of CMD leading to HFpEF. In this review article, we focus on the role of CMD in the pathogenesis of HFpEF resulting from cardiac remodeling and highlight the subsequent complexity of the EC-mediated correlation between CMD and HFpEF.