Connexin 50 Mutation Lowers Blood Pressure in Spontaneously Hypertensive Rat

0475945 - ÚMG 2018 RIV CZ eng J - Článek v odborném periodiku
Šeda, Ondřej - Liška, F. - Pravenec, Michal - Vernerová, Z. - Kazdová, L. - Křenová, D. - Zídek, Václav - Šedová, Lucie - Krupková, M. - Křen, V.
Connexin 50 Mutation Lowers Blood Pressure in Spontaneously Hypertensive Rat.
Physiological Research. Roč. 66, č. 1 (2017), s. 15-28. ISSN 0862-8408. E-ISSN 1802-9973
Grant CEP: GA ČR(CZ) GAP301/12/0696
Institucionální podpora: RVO:68378050 ; RVO:67985823
Klíčová slova: Connexin * Hypertension * Transcriptome * Animal models * Insulin resistance
Obor OECD: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (FGU-C)
Impakt faktor: 1.324, rok: 2017

We assessed the effect of the previously uncovered gap junction protein alpha 8 (Gja8) mutation present in spontaneously hypertensive ratdominant cataract (SHR-Dca) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR-Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR-Dca compared with SHR (P< 0.01 and P< 0.05, respectively, repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium, with no differences in expression between strains. SHR-Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basal insulin sensitivity in muscle. There were 21 transcripts common to the sets of 303 transcripts in kidney and 487 in heart showing > 1.2-fold difference in expression between SHR and SHR-Dca. Tumor necrosis factor was the most significant upstream regulator and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR-Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR-Dca strain, decreases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney.
Trvalý link: http://hdl.handle.net/11104/0272534