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Inhibitory effects of candesartan on KCa3.1 potassium channel expression and cell culture and proliferation in peripheral blood CD4+T lymphocytes in Kazakh patients with hypertension from the Xinjiang region
Authors:Hui Li  Jun-Ling Zhao  Su-Xia Han
Affiliation:1. Department of Internal Medicine (VIP) Unit 1, The First Affiliated Hospital of Xinjiang Medical University, Urimuqi, China;2. Graduate School, Xinjang Medical University, Urumqi, China;3. Department of Cardiology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, Research direction: The basic and clinical research of coronary heart disease
Abstract:Background and aim: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China.

Methods: Flow cytometry technology was used for T-lymphocyte subtype analysis. Changes in the messenger RNA and protein expression of the KCa3.1 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and western blots, using CD4+ T-cell samples from hypertensive Kazakh patients divided into candesartan and TRAM-34 treatment groups, and healthy case controls. Peripheral blood CD4+ T lymphocytes were activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and electron microscope photography.

Results: Expression of KCa3.1 was significantly higher in the hypertensive patients than in the controls (p < 0.05). Compared with the healthy group, Kazakh hypertensive patients had a reduced proportion of CD4+ T lymphocytes (p < 0.05).Candesartan and TRAM-34 intervention for 24 h and 48 h inhibited the expression of Kv1.3 and KCa3.1 at mRNA and protein level (p < 0.05).

Conclusions: Increase in functional KCa3.1 channels expressed in CD4+ T lymphocytes of Kazakh patients with hypertension was blocked by candesartan, providing theoretical support for hypertension treatment at the cellular ion channel level. Candesartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and KCa3.1 potassium channel expression in CD4 + T lymphocytes.

Keywords:Xinjiang Kazakh  CD4+T lymphocyte  KCa3.1 Potassium channel  Candesartan  Essential hypertension
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