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.

The role of lipoprotein discolloidosis and physicochemical metamorphosis of cholesterol occurring in the arterial intimal connective tissue in the induction of local manifestation of atherosclerosis – granulomatosis around endogenous foreign bodies is shown.

The paper shows that atherosclerosis results from disturbed cholesterol homeostasis in the body, the development of systemic stromal-vascular lipid-protein dystrophy (or lipidosis, or cholesterolosis) complicated by extracellular focal lipid deposits with a predominant cholesterol in the interstitial tissue of the inner arterial and aortic layer. These deposits are foreign to this body tissue. They induce the development of chronic productive granulomatous inflammation in it – granulomatosis around endogenous foreign bodies. Cholesterol deposition is promoted by a positive cholesterol balance in the body; increased permeability of the endothelium in hemodynamically vulnerable parts of the arteries, where blood components, including LP, infiltrate their wall; a lack of hydrolytic enzymes in the cell lysosomes that could destroy the steroid nucleus of the cholesterol molecule. Being essential for each specific organism (for building membranes, the formation of bile acids, the synthesis of steroid hormones, vitamin D3), cholesterol, if exceeded, can increase the probability of developing atherosclerosis. Genetic mechanisms are implicated in the disturbed lipid protein metabolism in the human body. Hyperlipoproteinemias (HLPs) are known to be the most common metabolic disorders. The dystrophy under consideration results from primary HLP types IIa, IIb, III, IV, V, as well as secondary HLPs in patients with various medical conditions associated with an increase in blood LDL and / or VLDL and/or a decrease in HDL. A reduced cholesterol efflux from peripheral tissues due to a decreased HDL content and the development of lipidosis are seen in diabetes, obesity, physical inactivity, stress, puberty, menopause, hypertriglyceridemia, cigarette smoking, uremia, treatment with anabolic steroids, beta-adrenergic blocking agents, gestagens, and the use of contraceptives. The most pronounced manifestations of dystrophy are characteristic of HLP types IIA, IIb, III, but its moderate development complicated by atherosclerosis also occurs in types IV and V, which are accompanied by increased blood VLDL. Mutations of LDL receptor genes, apoprotein genes lead to the development of stromal vascular dystrophy and atherosclerosis. A number of rare genetic disorders of sterol metabolism accompany impaired metabolism of cholesterol and its esters: hepatic lipase deficiency (with accumulation of VLDL and IDLs); a deficiency in lysosomal hydrolase of cholesterol esters with impaired LDL metabolism (Wolman disease); cholesterol ester accumulation disease; cerebrotendinous xanthomatosis; cerebral cholesterolosis; Toichlander and Hand Schüler Christian syndromes. The main factor contributing to the development of inflammation in the inner vascular wall of arteries and aorta in atherosclerosis is the cyclic hydrocarbonic structure of cholesterol, which cannot be cleaved in the lysosomes of MPs. The leading role of the cyclic hydrocarbonic structure of cholesterol, which is insoluble and indestructible by MPs, in the induction of atherosclerosis-related inflammation is confirmed by the fact of the atherogenic action of cholesterol derivatives having its structure. An important factor in inflammatory morphogenesis is the lipoprotein dyscolloidosis occurring in the arterial intima and the physical and chemical metamorphosis of cholesterol. A colloidal solution, solid crystals of free cholesterol and liquid crystals of cholesterol esters have a pronounced phlogogenic and sclerogenic effect on the interstitial tissue of the arterial intima.

У роботі у вигляді питань та відповідей на них продовжено виклад інформації, яка характеризує атеросклеротичне запалення в інтимі артерій як гранульоматоз, що індукується ендогенними чужорідними (сторонніми) тілами – депозитами холестерину (ХС). Всі численні теорії атеросклерозу (Ат), включаючи концепцію „відповіді на ушкодження“, не можуть пояснити, чому речовини, що мають вуглеводневе кільце холестерину (холестанол, В-ситостерол, кампестерол, стигмастерол, вітамін D, стерини його групи) мають атерогенні властивості. Вони не пояснюють характерну „архітектуру“ атером/бляшок, ідентичну структурі гранульом, індукованих сторонніми тілами. Всупереч уявленням авторів, основним фактором атерогенезу, тригером гранулематозного запалення при атеросклерозі є не структурно пошкоджені („модифіковані“) частинки ліпопротеїнів (ЛП) низької густини (ЛПНГ), а холестерин, що вивільняється з них у судинній стінці. Незалежно від того, в якому фізико-хімічному стані знаходиться, він не може бути зруйнований макрофагами. Зазвичай макрофаги захоплюють чужорідний і свій матеріал, що став чужорідним для тканини, і переробляють його за допомогою лізосомальних ферментів, активних форм кисню. Холестерин, що накопичився позаклітинно, вони зруйнувати не можуть. Той факт, що локальний запальний процес при атеросклерозі, викликається позаклітинним холестерином, підтверджується утворенням гранульом при введенні кристалічного холестерину в тканини тіла експериментальних тварин [3]. Пінисті клітини в основному є макрофагами, які продукують близько 60 біологічно активних речовин. Вони є основним фактором запального процесу, що розвивається в стінці артерій, його організаторами і регуляторами. Як пінисті клітини при атеросклерозі, так і їх аналоги – пилові клітини при пневмоконіозах, відображають незавершеність фагоцитозу і є причиною хронічного запального процесу.

In the literature there are no clinical and morphological data that would prove the participation of hypersensitivity reactions, autoimmune and immunocomplex processes in the development of granulomatosis in the arteries in atherosclerosis. In cholesterol mature macrophage granulomas (plaques), markers of immune inflammation are not detected - epithelioid and giant multinuclear Pirogov-Langhans cells; in xanthogranulomas there are giant multinucleated cells of foreign bodies. Granulomatosis in the arteries is induced by endogenous foreign bodies – lipid foci containing non-antigenic, non-hydrolysable cholesterol by macrophage lysosomal enzymes. The properties of its molecule, crystallization and insolubility in the blood and interstitial fluid are the cause of the unresolved nature of the developing inflammation in the arteries.