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      Shorter Leukocyte Telomere Length coupled with lower expression of Telomerase Genes in patients with Essential Hypertension

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          Abstract

          Background: The essential hypertension (EH) pathophysiology remains poorly understood. Many studies indicate that reduced leukocyte telomere length (LTL) is involved in the EH pathogenesis, however, the direct analysis of arterial telomere length (ATL) from EH patients and normotensive individuals did not show a difference. To address these discrepant observations between LTL and ATL, we performed comprehensive analyses of LTL, telomerase gene expression and their genetic variants in healthy normotensive controls and EH patients.

          Methods: Sex-matched 206 EH patients and equal numbers of healthy controls were recruited. LTL, and the expression of two key telomerase components, telomerase reverse transcriptase (TERT) and internal RNA template (TERC) were determined using qPCR. Genetic variants of rs2736100 at the TERT and rs12696304 at the TERC loci were determined using TaqMan genotyping kits.

          Results: LTL was significantly shorter in EH patients than in their normotensive controls (0.96 ± 0.52 vs 1.19 ± 0.58, P = 0.001). Moreover, TERT and TERC expression in patients' leukocytes were substantially lower compare to that in healthy controls (TERT, 0.98 ± 0.98 vs 1.76 ± 1.75, P = 0.003; TERC, 1.26 ± 1.62 vs 4.69 ± 3.61, P < 0.001). However, there were no differences in the genetic variants of rs2736100 and rs12696304 between patient and control groups.

          Conclusions: EH patients have significantly shorter LTL, which may result from defective TERT and TERC expression in leukocytes. Collectively, lower telomerase expression contributes to shorter LTL observed in EH patients, and telomerase activators may be considered for EH therapy.

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          Most cited references35

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          Telomere diseases.

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            Hypertension and aging.

            Hypertension is a highly prevalent condition with numerous health risks, and the incidence of hypertension is greatest among older adults. Traditional discussions of hypertension have largely focused on the risks for cardiovascular disease and associated events. However, there are a number of collateral effects, including risks for dementia, physical disability, and falls/fractures which are increasingly garnering attention in the hypertension literature. Several key mechanisms--including inflammation, oxidative stress, and endothelial dysfunction--are common to biologic aging and hypertension development and appear to have key mechanistic roles in the development of the cardiovascular and collateral risks of late-life hypertension. The objective of the present review is to highlight the multi-dimensional risks of hypertension among older adults and discuss potential strategies for treatment and future areas of research for improving overall care for older adults with hypertension.
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              Essential hypertension and oxidative stress: New insights.

              Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated, a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents, such as superoxide anion, and antioxidant molecules, and leads to a decrease in nitric oxide bioavailability, which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides, such as angiotensin II, endothelin-1 and urotensin II, act through their receptors to stimulate the production of reactive oxygen species, by activating enzymes like NADPH oxidase and xanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents, including vitamin C and E, N-Acetylcysteine, polyphenols and selenium, among others. These substances have different therapeutic targets, but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2020
                1 August 2020
                : 17
                : 14
                : 2180-2186
                Affiliations
                [1 ]Central Research Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, PR China.
                [2 ]Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, PR China.
                [3 ]Department of Medicine, Division of Hematology, Bioclinicum and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, SE-171 76 Solna, Sweden.
                Author notes
                ✉ Corresponding authors: Fengtao Wei, Department of Cardiology, the Second Hospital, Shandong University, Jinan, 250033, PR China. Phone: +86 17660080369; E-mail: mountain-wave@ 123456126.com , or; Dawei Xu, Department of Medicine, Bioclinicum, Karolinska Institutet and Karolinska University Hospital Solna, SE-171 76 Solna, Sweden. Phone: +46 8 51776552; E-mail: dawei.xu@ 123456ki.se .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijmsv17p2180
                10.7150/ijms.48456
                7484671
                32922179
                24b6a3ad-9d51-48a9-9623-f0577f9b130f
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 20 May 2020
                : 27 July 2020
                Categories
                Research Paper

                Medicine
                age-related disease,hypertension,et-1,telomerase,telomere
                Medicine
                age-related disease, hypertension, et-1, telomerase, telomere

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