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

Cardiovascular calcification is present in practically all cardiac diseases, which are the top killers in the world today ¹ , and is particularly associated with atherosclerosis ² , aortic stenosis ³ and rheumatic fever ⁴ . If not the direct cause of death, calcification contributes considerably to complications that can lead to heart failure ⁵ . Nonetheless, the origins and mechanisms of cardiovascular calcification are still strongly debated ^3,6–12 . 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 tissue ¹³ . These particles were found even before any sign of cardiac disease was present and were present in all stages of cardiac diseases ¹³ . 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 δ-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 calcification ^7,14 , 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.