Ketone Bodies in Cardiovascular Disease: The Vasculature as a Therapeutic Target

Evidence for the potential of ketone bodies (KBs) in the treatment of cardiovascular disease is growing rapidly. In addition to serving as sources of myocardial fuel, KBs exert an array of pleiotropic activities via multiple mechanisms. The vasculature is emerging as a key target of KBs. Recent small clinical studies have shown that the administration of exogenous KBs to patients with heart failure is associated with a marked reduction in systemic vascular resistance and improvement in myocardial function. Exogenous KBs have also been shown to increase coronary blood flow; decrease pulmonary vascular resistance; promote endothelial function and angiogenesis; increase skeletal muscle oxygenation and capillarization; and inhibit atherosclerosis, vascular calcification, and senescence. These vasculo-protective properties likely contribute to the beneficial effects of exogenous KBs observed in heart failure, pulmonary hypertension, and myocardial ischemia/infarction, and suggest potential wide applications in several other cardiovascular diseases and related conditions. In this review, we will discuss the salutary vascular effects of KBs and their cardioprotective roles.