title: Nebivolol induces distinct changes in profibrosis microRNA expression compared with atenolol, in salt-sensitive hypertensive rats.
abstract: Nebivolol is a selective β1-blocker with nitric oxide-enhancing effects. MicroRNAs are small noncoding RNA molecules that downregulate gene expression. We compared the effects of nebivolol and atenolol, a first generation β1-selective blocker, on left ventricular hypertrophy, fibrosis, and function and microRNA expression in a rodent model of hypertension. Dahl salt-sensitive rats received either low-salt chow (control) or AIN-76A high-salt (8% NaCl) diet and randomized to vehicle (high-salt), nebivolol (20 mg/kg per day), or atenolol (50 mg/kg per day) for 8 weeks. High-salt induced left ventricular hypertrophy and fibrosis and decreased the expression of miR-27a, -29a, and -133a. Nebovolol attenuated deterioration of left ventricular systolic function, remodeling, and fibrosis more than atenolol, despite similar effects on heart rate and blood pressure. Nebivolol, but not atenolol, prevented the decrease in miR-27a and -29a induced by high-salt. Nebivolol and atenolol equally attenuated the decrease in miR-133a. In vitro overexpression of miR-27a,-29a, and -133a inhibited cardiomyocyte hypertrophy and reduced collagen expression. Both miR-27a and -29a target Sp1, and miR-133a targets Cdc42. Pharmacological inhibition of Sp1 and Cdc42 decreased myocardial fibrosis and hypertrophy. Our data support a differential microRNAs expression profile in salt-induced hypertension. Nebivolol substantially attenuated cardiac remodeling, hypertrophy, and fibrosis more than atenolol. These effects are related to attenuation of the hypertension-induced decrease in miR-27a and -29a (with a subsequent decrease in Sp1 expression) and miR-133a (with a subsequent decrease in Cdc42).
authors: State Key Laboratory of Space Medicine Fundamentals and Application, Astronaut Research and Training Center of China, Beijing, People’s Republic of China.
authors: Hongmei
authors: H
authors: Ye
authors: Shukuan
authors: S
authors: Ling
authors: Alexander C
authors: AC
authors: Castillo
authors: Bejoy
authors: B
authors: Thomas
authors: Bo
authors: B
authors: Long
authors: Jinqiao
authors: J
authors: Qian
authors: Jose R
authors: JR
authors: Perez-Polo
authors: Yumei
authors: Y
authors: Ye
authors: Xiaoping
authors: X
authors: Chen
authors: Yochai
authors: Y
authors: Birnbaum
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000494:pharmacology*; D005355:Fibrosis; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D000068577:Nebivolol; D010865:Pilot Projects; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D007136:Immunoglobulins; C548234:MIRN133 microRNA, human; C531388:MIRN27 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C090698:SP1 antigen; D000068577:Nebivolol; D001262:Atenolol; D020764:cdc42 GTP-Binding Protein