AT1 receptor blocker azilsartan medoxomil normalizes plasma miR-146a and miR-342-3p in a murine heart failure model.
Our study measured circulating microRNA (miRNA) levels in the plasma of calsequestrin (CSQ)-tg mouse, a severe heart failure model, and evaluated whether treatment with angiotensin II type 1 receptor blocker, azilsartan medoxomil (AZL-M) influenced their levels using miRNA array analysis. MiR-146a, miR-149, miR-150, and miR-342-3p were reproducibly reduced in the plasma of CSQ-tg mice. Among them, miR-146a and miR-342-3p were significantly restored by AZL-M, which were associated with improvement of survival rate and reduction of congestion. These results suggest that miRNA, especially miR-146a and miR-342-3p, could be used as potential biomarkers for evaluating the efficacy of anti-heart failure drugs.
a Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division , Takeda Pharmaceutical Company Limited , Fujisawa , Japan.
Manami
M
Kaneko
a Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division , Takeda Pharmaceutical Company Limited , Fujisawa , Japan.
Tomoko
T
Satomi
a Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division , Takeda Pharmaceutical Company Limited , Fujisawa , Japan.
Shuji
S
Fujiwara
b Integrated Technology Research Laboratories, Pharmaceutical Research Division , Takeda Pharmaceutical Company Limited , Fujisawa , Japan.
Hidefumi
H
Uchiyama
a Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division , Takeda Pharmaceutical Company Limited , Fujisawa , Japan.
Keiji
K
Kusumoto
a Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division , Takeda Pharmaceutical Company Limited , Fujisawa , Japan.
Tomoyuki
T
Nishimoto
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D002155:Calsequestrin; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000097:blood*; D010069:Oxadiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D015996:Survival Rate
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D002155:Calsequestrin; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C529101:Mirn150 microRNA, mouse; C581863:Mirn342 microRNA, mouse; D010069:Oxadiazoles; C557413:azilsartan medoxomil
Azilsartan medoxomil; calsequestrin-tg mice; heart failure; microRNA; plasma