The study below demonstrates that vascular (and other soft tissue) calficiation depends on overpexression of the enzyme Poly (ADP-ribose) polymerase (PARP). Inhibiting the synthesis/activity of that enzyme prevented vascular calficiation, and as such can be a powerful prevention tool for CVD and in general any ischemic event. The study used minocycline (a tetracycline-family antibiotic) as PARP inhibitor. However, I find this strange and uncalled for, considering the most potent generic PARP inhibitor used clinically is niacinamide. And while minocycline is safe, niacinamide is likely even safer, especially for chronic use considering lack of effects on microbiome. Doses of niacinamide known to inhibit PARP in humans start around 1g, and 80%+ inhibition has been demonstrated in humans with doses of 1g taken 3 times daily. But for the people who want to replicate the study design, the HED of minocycline was 7mg/kg and was taken for 6 weeks.
https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30658-8
“…Biomineralization of the extracellular matrix is an essential, regulated process. Inappropriate mineralization of bone and the vasculature has devastating effects on patient health, yet an integrated understanding of the chemical and cell biological processes that lead to mineral nucleation remains elusive. Here, we report that biomineralization of bone and the vasculature is associated with extracellular poly(ADP-ribose) synthesized by poly(ADP-ribose) polymerases in response to oxidative and/or DNA damage. We use ultrastructural methods to show poly(ADP-ribose) can form both calcified spherical particles, reminiscent of those found in vascular calcification, and biomimetically calcified collagen fibrils similar to bone. Importantly, inhibition of poly(ADP-ribose) biosynthesis in vitro and in vivo inhibits biomineralization, suggesting a therapeutic route for the treatment of vascular calcifications. We conclude that poly(ADP-ribose) plays a central chemical role in both pathological and physiological extracellular matrix calcification.”
