The dissertation is devoted to the establishment of histogenetic stages and the corresponding morphological characteristics of the dendritic cells in the coronary arteries wall in experimental atherosclerosis.
Based on the histological, immunohistochemical, biochemical analysis of changes observed in the modeling of atherosclerosis in rats, it was found that the introduction of native human LDL in experimental rats is accompanied by a reaction from the coronary vessels of large, medium and small calibers, in which there are 4 stages: domorphological (4th - 7th week), dolipid (8th - 11th week), stages of lipoidosis (12th - 17th week) and liposclerosis (18th - 20th week).
It is shown that the earliest reaction in modeling of atherosclerosis is found in small caliber vessels. The all period of remodeling of the walls of the vessels was reflected in a significant increase the Wogenworth index: 1.7 times in the coronary arteries of the medium caliber and 2.3 times in the coronary arteries of the small caliber, indicating a gradual decrease in arterial capacity.
It was established that the histogenesis of coronary vascular dendritic cells during atherosclerotic lesions involves the differentiation of immature cells in the mature by changing the shape of the body and cell nucleus, gradually increasing the number of processes, as well as increasing the expression of the S-100 and CD1α. In the wall of the coronary arteries of the control animals and at the premorphological stage of the atherosclerotic process in the animals of the experimental group, were detected immature dendritic cells. Certainly atherosclerotic changes of the coronary vessels contained not only an increased number of immature dendritic cells, but also an increased number of DС at different stages of differentiation.
For the first time, it was proposed to separately the premorphological stage, which was characterized by changes in the histostructure in the coronary arteries of the small caliber and the primary reaction of the DС of conditional type 1 in response to the antigenic loading.
The deviations of the activity of MMP-2 and MMP-9 in the areas of atherosclerotic damage were noticed, reflecting the degree of degradation of the components of the extracellular matrix: the activity of MMP-2 increased from 74.55 ± 0.86 % on the 8th week, which corresponded to the dolipid stage, and gradually reached maximum values of 127.32 ± 0.99 % on the 20th week, which corresponded with the stage of liposclerosis; MMP-9 activity increased to 105.98 ± 0.68 % on the 9th week, which was associated with the dolipid stage, with a subsequent decrease to 86.69 ± 0.54 % on the 16th week, which corresponded to the stage of lipoidosis.
Several associations of morphological, histogenetic and biochemical features, which can be considered as criteria for each of the stages of experimental atherosclerosis, have been established. The criterion of the pre-morphological stage is a set of changes of the wall of coronary vessels of small caliber in the form of perivascular edema, histiocytic infiltration, an increase in the number of immature DC and the appearance of them in the media of the vessel. The dolipid stage is characterized by an increase in the number of mast cells, macrophages and leukocytes, increased the Wogenworth index, a rapid increase in the activity of MMP-2 and the appearance of DC with signs of differentiation. Symptoms of the lipoid stage are the expressive disorganization of the fiber and cellular components of the intima and media of the vessels of different calibres, the appearance of foam cells in the intima, the active migration of smooth myocytes due to the high level of MMP-2, the progression of the ripening of the DC with the parallel increase in the number of immature DC. The criterion of the stage of liposcleropsis is the association of the following signs: the presence of mature DC in the intima and media of vessels of various calibres against the background of high activity of MMP-2 and minimal activity of MMP-9, high the Wogenworth index and expressive amount of foam cells.
