CALCIFICATION OF ARTERIES IN PATIENTS WITH ATHEROSCLEROSIS: CAUSES AND MECHANISMS OF DEVELOPMENT

Abstract

The paper shows analogies between the mechanisms of calcification of arteries, various tissues and bone mineralization. In calcification the same mechanisms are involved, as at ossification of an organic matrix of a bone, including participation of stem cells. In the arteries and capillaries of various organs found polypotent precursors – mesenchymal stem cells, presumably responsible for the pathological mineralization of the arterial wall. Circulating in the blood and present in the intima of the human atheromatous aorta colony-forming stem cells of the stromal line of differentiation. Adventitia cells or pericytes are considered as a pluripotent mesenchymal reserve for replenishment of some cellular forms of connective tissue. Bone marrow stem cells of the stromal line of differentiation with the presence of pluripotent stromal cells in the blood and granulomas (plaques) and their transformation into bone tissue cells are involved in atherogenesis. Smooth muscle cells (SMCs) and myofibroblasts of the arterial wall adventitia have an osteoblast-like phenotype. Collagen and elastic fibers are involved in the calcification of blood vessels and soft tissues. Calcification of granulomas (plaques) accompanies their inflammatory morphogenesis, accompanied by the development of scar tissue. It often accompanies and completes the inflammation in them. This process is observed with the gradual replacement of the parenchyma of some organs with connective tissue. The mineral phase in bones and soft tissues, represented by calcium (Ca) and phosphate (P), contacts with nucleators - specific areas of collagen fibers. Non-collagen proteins are also involved in arterial calcification. With the progression of atherosclerosis and calcification of granulomas/plaques by cells present in the arterial wall, osteonectin is expressed. Osteopontin content is associated with Ca deposits in them; in particular, it correlates with the Ca level in the coronary arteries. In the processes of ossification and calcification, phosphatases play a certain role. In areas of calcification of granulomas/plaques, osteoprotegerin is found, which inhibits the activity of alkaline phosphatase in the aorta and prevents calcification of the media. Arterial wall calcification and inflammation are inhibited by fetuin-A and matrix γ-carboxyglutaric protein (MGP). The rate of bone formation and tissue calcification depends on the concentration of Ca and P in plasma and extracellular fluid. With their high concentration in the extracellular fluid, the mineral phase appears where it normally does not exist. Lipids are among the initiators of granuloma / plaque calcification in the arteries. The role of inflammation and necrosis in the calcification of the arteries is confirmed by experiments on animals with repeated intravenous injections of adrenaline, which causes focal necrosis of the middle membrane, which then undergoes calcification. In arterial walls, heart muscle, bone and cartilage tissue, osteonectin, osteocalcin, osteopontin, bone sialoprotein are often formed. In general, the mechanisms of arterial and soft tissue calcification are poorly understood. There are no effective remedies for calcification.