Rewiring Vascular Metabolism Prevents Sudden Death due to Aortic Ruptures-Brief Report

Abstract

BACKGROUND: The goal of this study was to determine whether boosting mitochondrial respiration prevents the development of fatal aortic ruptures triggered by atherosclerosis and hypertension. METHODS: Ang-II (angiotensin-II) was infused in ApoE (Apolipoprotein E)-deficient mice fed with a western diet to induce acute aortic aneurysms and lethal ruptures. RESULTS: We found decreased mitochondrial respiration and mitochondrial proteins in vascular smooth muscle cells from murine and human aortic aneurysms. Boosting NAD levels with nicotinamide riboside reduced the development of aortic aneurysms and sudden death by aortic ruptures. CONCLUSIONS: Targetable vascular metabolism is a new clinical strategy to prevent fatal aortic ruptures and sudden death in patients with aortic aneurysms. GRAPHIC ABSTRACT: A graphic abstract is available for this article. Key Words: aortic aneurysm ¿ aortic rupture ¿ DNA, mitochondria ¿ glycolysis ¿ mitochondrial respiration ¿ vascular metabolism