Angiogenesis of atherosclerotic plaques in patients with metabolic syndrome. In memoriam V. Anestiaids

Abstract

This article is the result of our long-term studies in the area of atherogenesis and continuing to date search for answers to unresolved issues, in cooperation with the Angiogenesis Research Center, the Victor Babes University of Medicine and Pharmacy (Timisoara, Romania). The results of these studies were presented at many national and international symposia and congresses. Numerous studies have demonstrated that endothelial damage is a precursory symptom of atherosclerosis, which leads to an increase of vascular permeability, activation of mast cells and migration of leukocytes, lymphocytes, macrophages, adhesion of platelets, proliferation of vascular smooth muscle cells and eventual vasospasm and pro-infl ammatory condition. All of the above listed components can be rightfully considered active pathogenetic participants in atherosclerosis and a result of aggregation of all risk factors that accompany a wide variety of cardiovascular diseases, such as coronary heart disease, hypertension, diabetes, dyslipidemia etc. The infl ux of monocytes and mast cells during the early stages of atherosclerosis leads to the most pronounced manifestations of vascular inflammation, especially in patients with metabolic disorders [1]. Angiogenesis is a very important pathogenetic element of atherosclerosis in stages of complicated plaques, along with mast cells and macrophages. CD-105 is a sensitive marker of newly formed endothelial cells, an effective index of activation and proliferation of microvessels, not only in aggressive forms of cancer, but also in atherosclerotic plaques of the affected vessels. The plaque neovascularization process often begins in intima, progresses and leads to further destabilization of atherosclerotic plaques (intramural hemorrhage, ruptures etc.). Also, anti- MCT (mast cell tryptase) and CD-68 demonstrate clearly the important pathogenetic stages and patterns of atherosclerosis development and its complications in patients with metabolic disorders. In our study, we analyzed the histotopographic distribution of newly formed blood vessels as a feature of angiogenesis, the extent of mast cell degranulation, the expression of macrophages in different types of plaques, as well as various arterial vessels in patients with atherosclerosis and metabolic syndrome, complicated by atherosclerosis. We have tried to analyze the importance of mast cells and macrophages, the patterns of development of atherosclerosis stages, along with diagnostic and prognostic features. The study included 34 patients, who died of atherosclerosis (no. =17) and atherosclerotic complications of metabolic syndrome (no. =17). Fragments of their cerebral (middle cerebral arteries), carotid, coronary arteries, aorta (thoracic and abdominal segments), renal, iliac and vertebral arteries were collected for research at autopsy. The fragments were processed using standard techniques. The type definition of plaques was based on morphological classification, as well as on macroscopic and histological images of hematoxylin-eosin stained sections and on histochemical methods – silver and orcein impregnation. To determine the expression of mast cells in the affected vessels, we have used anti-MCT immunohistochemical stain. Macrophages were identified using the CD-68 specific marker and the newly formed vessels – respectively, by using CD-105 (Endoglin), which is specific. The evaluation of the results was based on determining the density and intensity of the final reaction, reflected in the quantitative ratio of different zones of atheromatous plaques. Positively stained mast cells, macrophages and newly formed vessels were found in many types of atherosclerotic plaques, especially in adventitia and in the immediate vicinity of plaques and in subendothelial layers. We found a statistical correlation between the plaque type and clinical data. The immunohistochemical method is effective for determining mast cells, macrophages, and newly formed vessels of atherosclerotic plaques, directly reflecting many important pathogenetic elements of atherogenesis in patients with metabolic syndrome