Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm.

Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active research. In this review, we describe the morphological changes of the aortic wall in TAA. We outline the genetic disorders associated with aortic enlargement and discuss the potential role of mitochondrial pathology, in particular mitochondrial DNA heteroplasmy, in the disease pathogenesis.

[Inflammatory infiltrates, vasa vasorum, and endothelial NO synthase in the wall of thoracic aortic aneurysm]. / Vospalitel'nye infil'traty, vasa vasorum i NO-sintaza éndoteliia v stenke anevrizmy grudnogo otdela aorty.

OBJECTIVE: To elucidate whether there is a relationship between inflammation of the wall of aortic aneurysm and the number of vasa vasorum in it. MATERIAL AND METHODS: The investigation material was aortic aneurysm wall segments obtained during surgery. Among the patients, there were 20 men and 5 women. The patients' age ranged from 33 to 69 years. The investigation used monoclonal antibodies to macrophages (CD68), T cells (CD3, CD4, and CD8) and antibodies to von Willebrand factor, endothelial NO synthase, and alpha smooth muscle actin. A morphometric study was conducted. RESULTS: Calculation of the number of vasa vasorum (including newly formed vessels) in the adventitia of aortic aneurysm revealed that there was a statistically significant difference between the number of vasa vasorum in patients with an active inflammatory response (Group 1) versus Group 2 patients with a moderate inflammatory process in the aneurysm wall (p≤0.05) and a statistically significant difference between Groups 1 and 3 (without inflammatory infiltrates) (p≤0.05). Endothelial vasa vasorum heterogeneity was found in case of an immune response to NO synthase. At the same time individual vasa vasorium did not contain NO synthase, this enzyme was identified in the endothelium in a number of nearby vessels. CONCLUSION: The increase in the number of vasa vasorum in the aneurysm wall in patients with abundant inflammatory infiltrates is due to the fact that some of the inflammatory cytokines of T-cells and macrophages also contribute to angiogenesis.

[Gigantic aneurysm of the coronary artery]. / Gigantskaia anevrizma koronarnoi arterii.

The paper describes a clinical case of gigantic aneurysm of one of the coronary arteries. It considers the morphological and immunohistochemical characteristics of the wall of the blood vessel with the detected signs of coronaritis. The authors have determined that Kawasaki disease could be retrospectively diagnosed in early childhood.

[The heteroplasmy level of some mutations in gene MT-CYB among women with asymptomatic atherosclerosis].

Atherosclerosis is a polygenic socially significant disease whose risk factors include coronary heart disease, diabetes, hypertension, and myocardial infarction. According to the literature, mutations m.14846G>A (G34S), m.15762G>A (G339Q), m.15084G>A (W113Ter), and m.15059G>A (G190Ter) of cytochrome B gene (MT-CYB) are associated with mitochondrial myopathies, myoglobinuria, and exercise intolerance. Preliminary studies carried out by the authors made it possible to discover an association of certain mitochondrial genome mutations with atherosclerotic lesions of aortic intima in people who died as a result of an accident or sudden death. The most interesting seemed to be the data on the association of mutations m.14846G>A and m.15059G>A of the cytochrome B gene with lipofibrous aortic plaques, because these mutations affect the mitochondrial respiratory chain enzyme. Defects in the given chain may be the reason for the launch of pathogenic mechanisms in the human body. Owing to the fact that mutations in the mitochondrial genome are inherited by the maternal type, it was decided to analyze cytochrome B gene mutations in a sample of female volunteers from Moscow oblast. According to the findings, mutations m.14846G>A and m.15059G>A are highly significantly associated with atherosclerotic lesions of the carotid arteries: m.14846G>A is antiatherogenic and m.15059G>A is proatherogenic.

[Analysis of mitochondrial haplogroups in persons with subclinical atherosclerosis based on high-throughput mtDNA sequencing].

Genetic predisposition plays an important role among other risk factors in multifactorial socially significant diseases such as atherosclerosis and its clinical manifestations. This pilot study was aimed to identify the relationship between the type of mitochondrial haplogroup and the risk of subclinical atherosclerosis in humans. For accurate detection of mitochondrial haplogroups, high-throughput sequencing of the mitochondrial genome using the Roche 454 technology was carried out. The results have shown that in Russian population, the belonging to haplogroup H is associated with an increased risk of atherosclerosis, but belonging to haplogroups T and U--with reduced risk. The data obtained can be used to assess individual risk of atherosclerosis and for further studies on the role of mitochondrial genome mutations in the development of atherosclerosis and its clinical manifestations.