5359045 Nucleic acid coding for the human angiotensin converting enzyme (ACE), and its uses, especially for the in vitro diagnosis of arterial hypertension

Blood pressure disorder causes serious diseases in the cardiovascular system such as arterial hypertension. According to the World Health Organization, an estimated 1.13 billion people worldwide have hypertension, and most of them (two-thirds) live in low- and middle-income countries. It is poorly controlled and constitutes one of the leading causes of premature death. In Africa, nearly 40% of adults in many countries have high blood pressure, but most wouldn't even know it. In 2019, Algeria announced that 24% of the population suffers from the arterial hypertension and around 72% of those who were tested positive had not received treatment. Among the processes related to hypertension, the angiotensin converting enzyme I (ACE) plays an important role in the regulation of the blood pressure. The talk about the high potential of the hawthorn and rosemary plants to treat hypertension was so spread in the Algerian culture, which prompted to study the molecules of these plants and descript they behavior with the angiotensin-converting enzyme by calculating energy affinity. Using molecular docking approach, identification and evaluation of the inhibitory potential of ACE by selected herbs was attempted. In addition, and in order to identify the most suitable molecules which can be developed to oral drugs considering their adsorption, distribution, metabolism, and excretion (ADME), Lipinski’s rules were applied using free SwissADME tool. Our study provides clearer insight interaction properties of known putative inhibitors of ACE such as Caffeic acid, Quercetin, Luteolin, Eugenol, Rosmaquinone, and Rosmaquinone β, which may be developed into drugs after in-vitro and in-vivo tests and also encourage use of medicinal herbs for treatment of arterial hypertension.

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ASSOCIATION OF BDKRB2 AND ACE GENE POLYMORPHISM WITH ERYTHROCYTE ADRENOREACTIVITY IN YOUNG MEN WITH DIFFERENT MOTOR ACTIVITY

Ulyanovsk Medico-biological Journal ◽

10.34014/2227-1848-2020-1-96-107 ◽

2020 ◽

pp. 96-107

Author(s):

A.Z. Dautova ◽

E.A. Khazhieva ◽

V.G. Shamratova ◽

L.Z. Sadykova

Keyword(s):

Gene Polymorphism ◽

Angiotensin Converting Enzyme ◽

Motor Activity ◽

Receptor Gene ◽

Young Men ◽

Converting Enzyme ◽

Ace Gene ◽

Ace Gene Polymorphism ◽

Physically Inactive

The aim of the paper was to study the association of polymorphic variants of rs4646994 (I/D) of the angiotensin converting enzyme gene (ACE) and rs5810761 (+9/-9) of the bradykinin B2 receptor gene (BDKRB2) with erythrocyte adrenoreactivity (ARE) in athletes and untrained young men. Materials and Methods. The study involved 61 young men (aged 21–23) with different levels of motor activity (MA). ARE was evaluated according to the erythrocyte sedimentation rate (ESR) change under adrenaline in vitro at final concentrations 10-5, 10-6, 10-7, 10-9, 10-11, 10-13 g/ml of venous blood. According to the effect observed and ESR shifts under adrenaline, we distinguished 3 ARE types: antiaggregative (AnAg), areactive (Ar) and aggregative (Ar). Results. The results of comparative and correlation analyses demonstrated that young athletes with +9/-9 (BDKRB2) genotype were characterized by a higher aggregative resistance of erythrocytes to the effects of both physiological (<10-9 g/ml) (physiological adrenaline concentration, PAC) and stressful doses (>10-9 g/ml) of adrenaline (stress adrenaline concentration, SAC), as well as by predominance of AnAg and Ar ARE types. In athletes, among the representatives of different genotypes of АСЕ gene I/D polymorphism, the erythrocyte response to adrenaline did not have any statistically significant differences. In physically inactive students, namely individuals with the D/D genotype, maximal ESR deviation under PAC was less than in those with I/D genotype. Conclusion. Athletes with *-9 allele (+9/-9 genotype) in their genotype can be considered more stress-resistant, which is provided by optimal adaptive and compensatory body mechanisms. Apparently, resistance of cells to the adrenaline contributes much to the work of these mechanisms. As for the ACE gene polymorphism, its effect on the suspension characteristics of erythrocytes is less pronounced not only in physically inactive young men, but in athletes as well. Keywords: erythrocyte adrenoreactivity (ARE), stress tolerance, β2 bradykinin receptor gene (BDKRB2), angiotensin converting enzyme (ACE) gene, motor activity. Цель работы – изучить ассоциацию полиморфных вариантов rs4646994 (I/D) гена ангиотензинпревращающего фермента (АСЕ) и rs5810761 (+9/-9) гена рецептора брадикинина 2 типа (BDKRB2) с адренореактивностью эритроцитов (АРЭ) у спортсменов и юношей, ведущих физически малоактивный образ жизни. Материалы и методы. В исследовании принял участие 61 юноша с разным уровнем двигательной активности (ДА) в возрасте 21–23 лет. Оценку АРЭ проводили по изменению скорости оседания эритроцитов (СОЭ) под действием адреналина in vitro в конечных концентрациях 10-5, 10-6, 10-7, 10-8, 10-9, 10-11, 10-13 г/мл венозной крови. По характеру наблюдаемого эффекта в соответствии с направленностью сдвигов СОЭ в присутствии адреналина мы выделили 3 типа АРЭ: антиагрегационный (АнАг), ареактивный (Ар) и агрегационный (Аг). Результаты. По результатам сравнительного и корреляционного анализа установлено, что юноши-спортсмены с генотипом +9/-9 (BDKRB2) характеризуются более высокой агрегативной устойчивостью эритроцитов к воздействию как физиологических (10-9 г/мл и ниже), так и повышенных (стрессовых) доз (выше 10-8 г/мл крови) адреналина, а также преобладанием АнАг- и Ар-типов АРЭ. У представителей разных генотипов полиморфизма I/D гена АСЕ реакция эритроцитов на адреналин не имела статистически значимых различий в группе спортсменов, тогда как в группе малоактивных студентов у лиц с генотипом D/D максимальное отклонение СОЭ при ФКА было меньше, чем при генотипе I/D. Выводы. Спортсменов, имеющих в своём генотипе аллель *-9 (+9/-9 генотип), можно считать более стрессоустойчивыми, что обеспечивается оптимальными адаптивно-компенсаторными механизмами организма, существенная роль в обеспечении которых, по-видимому, принадлежит устойчивости клеток к действию адреналина. Что касается полиморфизма гена АСЕ, то его влияние на суспензионные характеристики эритроцитов выражено слабее не только у физически малоактивных юношей, но и у спортсменов. Ключевые слова: адренореактивность эритроцитов (АРЭ), стрессоустойчивость, ген рецептора брадикинина β2 (BDKRB2), ген ангиотензинпревращающего фермента (АСЕ), двигательная активность.

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