To further support the importance of the vasculature to HFpEF pathophysiology, several biomarkers related with vascular function are altered during HFpEF: reduced NO bioavailability (potent vasodilator), higher levels of endotelin-1 (a potent vasoconstrictor) and increased levels of plasminogen activator inhibitor-1 (PAI-1), a described risk factor for atherosclerosis, among others (52). The gene discussed is SERPINE1; the disease is atherosclerosis.