title: MiR-19a overexpression contributes to heart failure through targeting ADRB1.
abstract: Beta1-adrenoreceptor (β1-AR) predominantly exists in the heart and β1-AR reduction is closely related to severity of heart failure (HF). In this study, our research focused on the miRNAs that may repress β1-AR directly, and aim to find out new markers and target molecules for HF. We first did Argonaute2 AGO2 knock down experiments and confirmed that endogenous adrenoceptor beta 1 (ADRB1) expression was suppressed by miRNAs. To further identify which miRNA suppress ADRB1 expression directly, we constructed the ADRB1 3'UTR reporter plasmid and selected sixteen candidate miRNAs. Confirmed by dual-luciferase assay and western blot, we found that miR-19a suppressed ADRB1 expression by directly targeting 3'UTR. Further expressions detection the levels of miR-19a, BNP and cAMP in 32 plasma samples of HF patients helped us to construct positive correlations between the expression levels of miR-19a and BNP or cAMP, hints miR-19a may be used as a biomarker in HF patients indicating cardiac function. In conclusion, this study confirmed miR-19a suppressed ADRB1 expression by directly targeting 3'UTR of ADRB1 and found an positive correlation between plasma miR-19a and BNP or cAMP levels in HF patients, which may contributes to fully understand the HF pathogenesis and develops new therapy for HF.
authors.affiliation: Department of Health & Heart Center, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Cardiovascular, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Health & Heart Center, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
keywords: 3’ untranslated region; ADRB1; Heart failure; miRNA