# Diabetes‐induced vascular calcification is associated with low pyrophosphate and its oral supplementation prevents calcification in diabetic mice

## TL;DR

Diabetes can cause dangerous blood vessel calcification, but giving pyrophosphate orally can prevent it in mice.

## Contribution

This study shows that low pyrophosphate levels in diabetes contribute to calcification, and oral supplementation can prevent it.

## Key findings

- Diabetic patients and mice had reduced plasma pyrophosphate levels.
- Oral pyrophosphate treatment prevented vascular calcification in diabetic mice.
- TNAP inhibition restored pyrophosphate levels and reduced calcification.

## Abstract

The predominant cause of death among diabetic patients comes from cardiovascular complications, including vascular calcification. The objectives of this study were to improve the understanding of the molecular mechanisms involved in diabetes‐related calcification and to test potential preventive therapies. We found that levels of plasma pyrophosphate—a potent inhibitor of calcification—were decreased in type 1 and type 2 diabetic patients with cardiovascular symptoms. To further investigate vascular calcification, we developed a diabetic mouse model that showed increased aorta and renal calcification compared to control. Alkaline phosphatase activity was also increased in the circulation of diabetic mice, which resulted in a significant decrease in plasma pyrophosphate. Oral treatment with pyrophosphate prevented diabetes‐induced calcification in mice, providing a direct translational value for clinical applications.

Induction of diabetes in three different mouse strains uniformly resulted in an increase in TNAP activity and a reduction in pyrophosphate (PPi) in the circulation. Inhibition of TNAP restored plasma PPi. Diabetes‐induced calcification in the media layer of the aorta was detected only in the Abcc6−/− strain, which is predisposed to ectopic calcification. Orally given PPi rescued the calcification phenotype.