Biomineralization from platelet δ-granules as the origin of cardiovascular calcification in humans and other animals.

Abstract

Cardiovascular calcification is present in practically all cardiac diseases, which are the top killers in the world today1, and is particularly associated with atherosclerosis2, aortic stenosis3 and rheumatic fever4. If not the direct cause of death, calcification contributes considerably to complications that can lead to heart failure5. Nonetheless, the origins and mechanisms of cardiovascular calcification are still strongly debated3,6-12. Just over a decade ago, it has been reported that nano and micron-sized calcified spherical particles, formed from a single crystal of magnesium-containing calcium phosphate, were the first calcified structure that could be detected in cardiovascular tissue13. These particles were found even before any sign of cardiac disease was present and were present in all stages of cardiac diseases13. The ubiquity of these particles suggests their importance for the origins and development of cardiovascular calcific diseases. Here, we show that these particles originate from platelet {delta}-granules and are present in mammals, birds and lizards. Based on our results, we suggest a new mechanism for the origins of these particles, complementing existing models of cardiovascular calcification7,14, and bringing a new, early, and hitherto unaccounted key event in the process of cardiovascular calcification. This new mechanism model, along with a better understanding of the early stages of cardiovascular calcification, could open the path for the development of pharmacological prevention and treatment solutions for several cardiac diseases.