The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets

The vascular endothelial growth factor (VEGF) family, the crucial regulator of angiogenesis, lymphangiogenesis, lipid metabolism and inflammation, is involved in the development of atherosclerosis and further CVDs (cardiovascular diseases). This review discusses the general regulation and functions of VEGFs, their role in lipid metabolism and atherosclerosis development and progression. These functions present the great potential of applying the VEGF family as a target in the treatment of atherosclerosis and related CVDs. In addition, we discuss several modern anti-atherosclerosis VEGFs-targeted experimental procedures, drugs and natural compounds, which could significantly improve the efficiency of atherosclerosis and related CVDs’ treatment.

Prospects of using cilostazol in combined treatment of patients with obliterating atherosclerosis of lower limb arteries

Despite intensive study of pathophysiology, of molecular and cell mechanisms of progression of atherosclerosis, development and introduction of a wide range of new conservative and surgical treatment methods, until now the diseases of lower limb arteries (DLLA) are one of the most urgent problems of the modern vascular surgery and medicine in general. Intensive development of roentgen-endovascular methods of treatment for the diseases of lower limb arteries has led to a considerable revision of the tactics of management of this category of patients in the recent years. Despite the achievements of roentgen-endovascular surgery, frequency of obstructions after surgical revascularization of limbs remains high, both in early and late postoperative periods. It should also be noted that despite the intensive development of methods of therapy of patients with DLLA, frequency of limbs amputation in this category of patients remains high. One of the urgent problems of management of patients with DLLA after endovascular treatment is the problem of restenosis. In the recent years, new efficient methods of pharmacotherapy of DLLA have been developed and introduced into clinical practice, which allows significant improvement of medical prognosis in this category of patients and improvement of the outcomes. It should be noted that standard approaches to antithrombotic therapy in patients after endovascular surgeries based on use of antiaggregant drugs, can only decrease the rate of thrombotic complications, but not of restenosis, which, from the point of view of pathophysiology, is mainly hyperproliferative condition. Among promising approaches to treatment of restenosis, there is use of cilostazol, efficiency of which after endovascular surgeries on coronary and peripheral arteries has been proven in a number of studies.

Geneti c Traits of Brachiocephalic Atherosclerosis

Background. According to the World Health Organization, the atherosclerosis development depends on the quality of life and lifestyle (60 %), genetic (20 %), environmental factors (10 %) and quality of medical aid (5 %). The routes to defeat atherosclerosis generally and certain systemic enzyme disorders in particular pertain in research into the population genetic predispositions to this pathology.Materials and methods. A comparative study of genetic predispositions to malignant brachiocephalic atherosclerosis analysed the renin—angiotensin system gene association in 60 patients. Th e renin—angiotensin system allelic and polymorphic loci haplotype frequencies have been determined.Results and discussion. Patients with atherosclerotic brachiocephalic vascular lesions revealed a statistically significant frequency of the AGT gene’s allele C involved in coronary heart disease development.Conclusion. Th e study suggests a putative involvement of the angiotensinogen system genes in mediating the development of brachiocephalic atherosclerosis and coronary heart disease

Functional Active Genomics of Isoprene Biogenesis and resistance to cardiovascular diseases

The pathologic development of the atherosclerotic process is often associated with the metabolism of saturated and unsaturated fatty acid. Substitution of the saturated fatty acids in nutrition for polyunsaturated fatty acids is traditionally associated with the lowering of risk of coronary breaches rise. Understanding the molecular mechanisms of the atherosclerosis development and progress is very important for early diagnostic and effective medical treatment of the above-mentioned disease. After a thorough analysis of the data available on the pathological atherosclerotic process, we have come to the conclusion that this disease begins from vascular smooth muscle cell (VSMC) impaired function. In the basis of the atherosclerosis development lies isoprenes biogenesis breach, caused by cholesterol and the products of its metabolism. Atherosclerosis is a chronic inflammatory disease of the media wall of large- and medium-sized arteries. And endothelium injury is a consequence of the pathologic process progressing in myocytes. Metabolic problems have become so relevant that it is time to form a metabolic policy. Real target programs for the prevention of the development of metabolic diseases and their diagnostics in the early stages of development should be developed. But in order to achieve this goal, it is necessary to know the real molecular mechanism of development of the early stages of metabolic diseases. It is necessary to recognize that the research work on the metabolic problem was carried out mainly in the plane of the functionally-energy parameter and captures only the consequences of the pathological process. And the very reason and early stages of metabolic diseases remained hidden from us, as they are depending on the pathology in the plane Regulatory, Information, Coordination and Functional active bioenergy system.

High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging

Endoglin is a 180 kDa transmembrane glycoprotein that was demonstrated to be present in two different endoglin forms, namely membrane endoglin (Eng) and soluble endoglin (sEng). Increased sEng levels in the circulation have been detected in atherosclerosis, arterial hypertension, and type II diabetes mellitus. Moreover, sEng was shown to aggravate endothelial dysfunction when combined with a high-fat diet, suggesting it might be a risk factor for the development of endothelial dysfunction in combination with other risk factors. Therefore, this study hypothesized that high sEng levels exposure for 12 months combined with aging (an essential risk factor of atherosclerosis development) would aggravate vascular function in mouse aorta. Male transgenic mice with high levels of human sEng in plasma (Sol-Eng+) and their age-matched male transgenic littermates that do not develop high soluble endoglin (Control) on a chow diet were used. The aging process was initiated to contribute to endothelial dysfunction/atherosclerosis development, and it lasted 12 months. Wire myograph analysis showed impairment contractility in the Sol-Eng+ group when compared to the control group after KCl and PGF2α administration. Endothelium-dependent responsiveness to Ach was not significantly different between these groups. Western blot analysis revealed significantly decreased protein expression of Eng, p-eNOS, and ID1 expression in the Sol-Eng+ group compared to the control group suggesting reduced Eng signaling. In conclusion, we demonstrated for the first time that long-term exposure to high levels of sEng during aging results in alteration of vasoconstriction properties of the aorta, reduced eNOS phosphorylation, decreased Eng expression, and altered Eng signaling. These findings suggest that sEng can be considered a risk factor for the development of vascular dysfunction during aging and a potential therapeutical target for pharmacological intervention.

GPR55 Antagonist CID16020046 Protects against Atherosclerosis Development in Mice by Inhibiting Monocyte Adhesion and Mac-1 Expression

GPR55 recognizes several lipid molecules such as lysophosphatidylinositol. GPR55 expression was reported in human monocytes. However, its role in monocyte adhesion and atherosclerosis development has not been studied. The role of GPR55 in monocyte adhesion and atherosclerosis development was investigated in human THP-1 monocytes and ApoE−/− mice using O-1602 (a potent agonist of GPR55) and CID16020046 (a specific GPR55 antagonist). O-1602 treatment significantly increased monocyte adhesion to human umbilical vein endothelial cells, and the O-1602-induced adhesion was inhibited by treatment with CID16020046. O-1602 induced the expression of Mac-1 adhesion molecules, whereas CID16020046 inhibited this induction. Analysis of the promoter region of Mac-1 elucidated the binding sites of AP-1 and NF-κB between nucleotides −750 and −503 as GPR55 responsive elements. O-1602 induction of Mac-1 was found to be dependent on the signaling components of GPR55, that is, Gq protein, Ca2+, CaMKK, and PI3K. In Apo−/− mice, administration of CID16020046 ameliorated high-fat diet-induced atherosclerosis development. These results suggest that high-fat diet-induced GPR55 activation leads to the adhesion of monocytes to endothelial cells via induction of Mac-1, and CID16020046 blockage of GPR55 could suppress monocyte adhesion to vascular endothelial cells through suppression of Mac-1 expression, leading to protection against the development of atherosclerosis.

Atherosclerosis pathogenesis from the perspective of microvascular dysfunction

The article discusses different points of view on atherosclerosis development. The facts confirming the lipid hypothesis are presented. Attention is drawn to the possible participation of vasa vasorum in the development of atherosclerosis.

Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis

Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.