Inhibition of mitochondrial phosphate carrier prevents high phosphate-induced superoxide generation and vascular calcification

Abstract

Vascular disease: Phosphate transport protein implicated in blood vessel stiffening Drugs that block the transport of phosphate ions into mitochondria, the ‘powerhouses’ of the cell, could prevent life-threatening stiffening of blood vessel walls. Using smooth muscle cells taken from rat aortas, Kyu-Sang Park of Yonsei University Wonju College of Medicine, South Korea, and colleagues showed how mitochondrial uptake of phosphate via phosphate transport proteins triggered toxic metabolite generation, increased activity of bone formation genes and other reactions that collectively drive the deposition of minerals, leading to vascular stiffening. Suppression of the proteins’ activity, either using drug-like compounds or by genetic means, reduced these pathological changes in mice. The findings highlight the therapeutic potential of such an approach in people with elevated serum phosphate leading to calcium build-up within their vessel walls, a major risk factor for cardiovascular disease.