Study demonstrates how dietary phosphate can increase heart disease risk

High phosphate levels cause a stress signal inside the cells that line blood vessels, leading to the release of microparticles that promote the formation of blood clots.

A new study conducted by researchers at the University of Leicester in England has found that high phosphate levels can cause a stress signal inside the cells that line blood vessels, leading to the release of microparticles that promote the formation of blood clots. The study, “Hyperphosphatemia, Phosphoprotein Phosphatases, and Microparticle Release in Vascular Endothelial Cells,” is published in the Journal of the American Society of Nephrology.

Inorganic phosphate is a nutrient in nearly all diets. Because patients with chronic kidney disease (CKD) lose the ability to excrete excess phosphate in their urine, the nutrient accumulates in their blood and cells. Such “hyperphosphatemia” is thought to be an important contributor to CKD patients’ increased risk of cardiovascular disease.

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To investigate the link between hyperphosphatemia and cardiovascular disease link, a team led by Alan Bevington, BA, DPhil and PhD student Nima Abbasian, BSc, MSc, from the University of Leicester, examined the effects of hyperphosphatemia on the cells that form the lining of blood vessels. The researchers’ experiments revealed a mechanism by which an excess of inorganic phosphate—similar to levels found in the blood of CKD patients—causes a stress signal inside these cells. In cells that are stressed in this way, fragments known as microparticles break off from the cells and can promote the formation of blood clots.

“This is important because blocking of blood vessels by blood clots—a process known as thrombosis—is a common cause of injury and death, occurring in a wide range of human illnesses including CKD,” said Bevington.

While the effects described in this study are especially relevant to patients with kidney dysfunction who lose the ability to excrete excess phosphate in their urine, nearly all modern Western diets are rich in phosphate, so even healthy individuals with normally functioning kidneys may experience some elevation of blood phosphate levels. In addition, there are a number of metabolic disturbances that can raise phosphate levels inside cells. “It’s possible therefore that the results of this study will also be relevant in other situations in addition to CKD,” said Abbasian.

Study co-authors include James Burton, BA, MBChB, MRCP, DM, Karl Herbert, BSc, PhD, Barbara-Emily Tregunna, BSc, MSc, Jeremy Brown, BSc, MSc, Maryam Ghaderi-Najafabadi, BSc, MSc, Nigel Brunskill, MBChB, ECFMG, PhD, FRCP, and Alison Goodall, BSc, PhD.