Figure 2.

Role of system-wide endothelial dysfunction in HFpEF pathophysiology. Comorbidities induce systemic inflammation, creating oxidative stress in endothelial cells system-wide. Reduced NO bioavailability through reduction of NO to ONOO⁻ causes endothelial dysfunction. In different vascular beds, endothelial dysfunction has heterogeneous effects, which manifest as the cardinal HFpEF symptom of exercise intolerance. COPD=chronic obstructive pulmonary disease, CRP=C-reactive protein, ED=endothelial dysfunction, IL-6=interleukin-6, NO=nitric oxide, ONOO⁻=peroxynitrite, ROS=reactive oxygen species, RV=right ventricle, TNFα=tumor necrosis factor alpha.