AT1 blockade abolishes left ventricular hypertrophy in heterozygous cMyBP-C null mice: role of FHL1

• Published in: Fundamental & clinical pharmacology 2014-06, Vol.28 (3), p.249-256
• Main Authors: Vignier, Nicolas, Le Corvoisier, Philippe, Blard, Charlotte, Sambin, Lucien, Azibani, Feriel, Schlossarek, Saskia, Delcayre, Claude, Carrier, Lucie, Hittinger, Luc, Su, Jin Bo
• Format: Article
• Language: English
• Subjects: Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; AT1 receptor blockade; Biological and medical sciences; Biphenyl Compounds - administration & dosage; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Blood Pressure - drug effects; Cardiology. Vascular system; Carrier Proteins - genetics; Disease Models, Animal; Echocardiography; four-and-a-half LIM domains 1 protein; gene expression; Heart; Heterozygote; hypertrophic cardiomyopathy; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - genetics; Hypertrophy, Left Ventricular - metabolism; Hypertrophy, Left Ventricular - pathology; Intracellular Signaling Peptides and Proteins - metabolism; LIM Domain Proteins - metabolism; Linear Models; Medical sciences; Mice, Knockout; Muscle Proteins - metabolism; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Myocardium - pathology; myosin-binding protein C; Organ Size - drug effects; Pharmacology. Drug treatments; Tetrazoles - administration & dosage; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; the renin-angiotensin system; Ventricular Function, Left
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12031

This research investigated the impact of angiotensin AT1 receptor (Agtr1) blockade on left ventricular (LV) hypertrophy in a mouse model of human hypertrophic cardiomyopathy (HCM), which carries one functional allele of Mybpc3 gene coding cardiac myosin‐binding protein C (cMyBP‐C). Five‐month‐old heterozygous cMyBP‐C knockout (Het‐KO) and wild‐type mice were treated with irbesartan (50 mg/kg/day) or vehicle for 8 weeks. Arterial blood pressure was measured by tail cuff plethysmography. LV dimension and function were accessed by echocardiography. Myocardial gene expression was evaluated using RT‐qPCR. Compared with wild‐type littermates, Het‐KO mice had greater LV/body weight ratio (4.0 ± 0.1 vs. 3.3 ± 0.1 mg/g, P