Updates on the endothelial glycocalyx in heart failure with preserved ejection fraction

The endothelial glycocalyx (GCX) is a specialized form of extracellular matrix with a dynamic synthesis and degradation balance. It plays a pivotal role in regulating cell signaling, sensing the extracellular environment, and maintaining vascular permeability. In the setting of heart failure (HF), particularly in HF with preserved ejection fraction (HFpEF), systemic endothelial GCX degradation may represent an early pathophysiological mechanism. Indeed, HFpEF results from comorbidities-related proinflammatory states leading to endothelial dysfunction and subsequent myocardial hypertrophy, fibrosis, and stiffening. Endothelial GCX degradation is mainly triggered by matrix metalloproteinases, specific degradation enzymes (heparanase, hyaluronidase), or reactive oxygen species (ROS). Preservation or restoration of endothelial GCX function via GCX components' injection, enzyme inhibitors, anticoagulants, or dietary supplements has increasingly emerged as a promising approach to limit HFpEF progression. This review provides an overview of GCX degradation markers in HFpEF and summarizes current knowledge on the possible GCX's role in HFpEF pathophysiology.