According to modern concept of the etiopathogenesis of essential hypertension, immune cells play an important role in its development. Mediators produced by immunocompetent cells participate in the initiation and maintenance of chronic systemic inflammation and promote the development of vascular remodeling which is an important part of the pathogenesis of the disease and target organ damage. The immune mechanisms underlying blood pressure elevation include the activation of innate and adaptive immune cells. Endothelial damage triggers an inflammatory cascade, causing migration of the immune cells to the inflammatory site, mediated by chemokines and adhesion molecules. Macrophage infiltration of perivascular tissue contributes to impaired vasodilation and damage to target organs due to the production of active forms of oxygen. Angiotensin II also causes T cell infiltration of perivascular adipose tissue and adventitia and an increased production of tumor necrosis factor alpha and interferon gamma. In addition, T lymphocytes express the mineralocorticoid receptor involved in the development of systemic hypertension. An important role in the progression of hypertension belongs to interleukin-17, which is involved in blood pressure elevation and vascular remodeling. The review also contains data on the effect of gut microbiota on the regulation of blood pressure and the development of hypertension.
Согласно одной из современных концепций старения и долголетия человека, причиной деградации эндогенных процессов является повышение нестабильности генома с возрастом. К факторам генетической нестабильности относятся транспозоны, или мобильные генетические элементы. В геноме человека широко распространены Alu-ретротранспозоны. Среди членов данного семейства AluYa5 и AluYb8 являются единственными, сохранившими транспозиционную активность. С целью проверки гипотезы о роли активности транспозонов AluYa5 и AluYb8 в старении и долголетии человека проведен сравнительный анализ уровня их экспрессии среди лиц разного возраста. В исследовании приняли участие 75 здоровых жителей Республики Башкортостан в возрасте от 21 до 97 лет. Общая выборка дифференцирована на возрастные группы: среднюю (38 человек, 21-39 лет), старческую (23 человека, 82-89 лет) и группу долгожителей (14 человек, 90-97 лет). Образцы РНК выделяли из лейкоцитов периферической венозной крови стандартным тризольным методом. Количественный анализ содержания AluYa5-РНК и AluYb8-РНК в лейкоцитах крови проводили методом ПЦР в реальном времени. Относительное количество мРНК определяли с помощью ΔΔCt-метода. Сравнение возрастных групп проводили с использованием однофакторного дисперсионного анализа Краскела-Уоллиса. В общей анализируемой выборке показатели относительного уровня экспрессии субсемейств AluYa5 и AluYb8 составили 0,84 и 0,80 отн. ед. соответственно. Согласно сравнительному анализу относительного уровня AluYa5-РНК и AluYb8-РНК в лейкоцитах крови людей, относящихся к трем возрастным группам, не наблюдается статистически значимых различий в экспрессии транспозонов семейств AluYa5 (Н=3,59, p=0,17) и AluYb8 (Н=2,65, p=0,27). После объединения групп лиц старческого возраста и долгожителей и сравнения их с лицами среднего возраста различия в показателях значений медианы также не достигли уровня статистической значимости (p=0,1). При этом у людей в возрасте 82 лет и старше наблюдается более низкий уровень экспрессии Alu-элементов субсемейства AluYa5 (0,75 против 2,69 отн. ед.) и AluYb8 (0,73 против 2,15 отн. ед.). Таким образом, в исследованной выборке не было обнаружено статистически значимых изменений относительного уровня экспрессии субсемейств AluYa5 и AluYb8 с возрастом. According to one of the modern concepts of human aging and longevity, the cause of the degradation of endogenous processes is the increased genome instability with age. Factors of genetic instability include transposons, or mobile genetic elements. Alu-retrotransposons are ubiquitous in the human genome. Among the members of this family, AluYa5 and AluYb8 are the only ones that retained transpositional activity. To test the hypothesis about the role of of AluYa5 and AluYb8 transposons activity in human aging and longevity, we performed the comparative analysis of their expression level among individuals of different ages. The study group included 75 healthy residents of the Republic of Bashkortostan aged between 21 and 97 years. The total sample was divided into the following groups according to age: middle-aged (38 people, 21-39 years old), elderly (23 people, 82-89 years old) and a group of long-livers (14 people, 90-97 years old). RNA samples were isolated from leukocytes of peripheral venous blood by the standard method using Trizol reagent. Quantitative analysis of AluYa5-RNA and AluYb8-RNA in blood leukocytes was performed by real-time PCR. The relative amount of mRNA was determined using the ΔΔCt method. Comparison of age groups was carried out using one-way analysis of variance with the Kruskal-Wallis test. In the total analyzed sample, the expression levels of AluYa5 and AluYb8 were 0.84 and 0.80 rel. units respectively. According to the results of comparative analysis of AluYa5-RNA and AluYb8-RNA in blood leukocytes of people from three age groups, there were no statistically significant differences in the expression of AluYa5 (H = 3.59, p = 0.17) and AluYb8 (H = 2.65, p = 0.27). After combining the groups of elderly people and long-livers and comparing them with middle-aged people, the differences in the median values also did not reach the level of statistical significance (p = 0.1). At the same time, people aged 82 and older demonstrated lower level of expression of AluYa5 subfamily (0.75 versus 2.69 rel. units) and AluYb8 subfamily (0.73 versus 2.15 rel. units). There were no statistically significant changes in the relative expression level of the AluYa5 and AluYb8 subfamilies with age in the study group.
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