Natural history of calcium deposits in atherosclerosis progression and regression

Abstract

Calcium deposits emerge in young people as granules of microscopic size in atherosclerotic lesions defined histologically are type IV. Granules are found among the vast quantity of extracellular lipid droplets and cell remnants that form the core of this lesion type, and intracellularly within smooth muscle cells that have been disrupted and impaired by the accumulated extracellular material. Extracellular calcium granules are, in part, granules that formed intracellularly and were set free through cell death, and in part they represent extracellular calcification of cell remnants. Extracellular granules combine and grow to form large structures until, in adults past the fourth decade of life, the greater part of a lesion core may be calcified (type VII lesion). Organization of calcium deposits into bone (osseous metaplasia) may occur as a late step. The fate of human lesion components subsequent to therapeutic lowering of high blood cholesterol is not known. In rhesus monkeys, 3 1/2 years of drastic reduction of high blood cholesterol resulted in complete loss of macrophages, macrophage foam cells, and lymphocytes and loss or reduction of extracellular accumulations of lipid and cell remnants from advanced lesions. Calcium deposits, however, remained in the arterial wall and were not visibly changed. Osseous metaplasia of calcium deposits did not occur in monkeys over a 9-year period of lesion progression and regression.