Vascular calcification in diabetes: mechanisms and implications. Snell-Bergeon Janet K,Budoff Matthew J,Hokanson John E Current diabetes reports Cardiovascular disease (CVD) remains the leading cause of death among adults with diabetes, and CVD prevention remains a major challenge. Coronary artery calcium (CAC) score measured by electron beam tomography (EBT) or multi-slice detector computed tomography correlates closely with plaque burden and coronary angiography, and predicts coronary events independently of other risk factors. Further, progression of CAC over several years has been shown to predict increased mortality. Coronary calcification is an active process strongly associated with atherosclerotic plaque evolution and is an accepted surrogate endpoint in studies of patients with diabetes older than 30. In this review, recent findings regarding the mechanisms and implications of vascular calcification in diabetes will be discussed. 10.1007/s11892-013-0379-7

Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arteriosclerosis, thrombosis, and vascular biology This review centers on updating the active research area of vascular calcification. This pathology underlies substantial cardiovascular morbidity and mortality, through adverse mechanical effects on vascular compliance, vasomotion, and, most likely, plaque stability. Biomineralization is a complex, regulated process occurring widely throughout nature. Decades ago, its presence in the vasculature was considered a mere curiosity and an unregulated, dystrophic process that does not involve biological mechanisms. Although it remains controversial whether the process has any adaptive value or past evolutionary advantage, substantial advances have been made in understanding the biological mechanisms driving the process. Different types of calcific vasculopathy, such as inflammatory versus metabolic, have parallel mechanisms in skeletal bone calcification, such as intramembranous and endochondral ossification. Recent work has identified important regulatory roles for inflammation, oxidized lipids, elastin, alkaline phosphatase, osteoprogenitor cells, matrix γ-carboxyglutamic acid protein, transglutaminase, osteoclastic regulatory factors, phosphate regulatory hormones and receptors, apoptosis, prelamin A, autophagy, and microvesicles or microparticles similar to the matrix vesicles of skeletal bone. Recent work has uncovered fascinating interactions between matrix γ-carboxyglutamic acid protein, vitamin K, warfarin, and transport proteins. And, lastly, recent breakthroughs in inherited forms of calcific vasculopathy have identified the genes responsible as well as an unexpected overlap of phenotypes. Until recently, vascular calcification was considered a purely degenerative, unregulated process. Since then, investigative groups around the world have identified a wide range of causative mechanisms and regulatory pathways, and some of the recent developments are highlighted in this review. 10.1161/ATVBAHA.113.302070