Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-deficient mice.
BACKGROUND
Angiotensin II (AT) is implicated in the development of cardiac remodeling, which leads to heart failure, and pharmacological inhibition of the AT type 1 (AT1) receptor has improved mortality and morbidity in patients of heart failure. The aim of this study was to elucidate the role of the AT1 receptor in disease progression in muscle LIM protein (MLP)-deficient mice, which are susceptible to heart failure because of defective function of mechanosensors in cardiomyocytes.


RESULTS
Hearts from MLP knockout (MLPKO) mice and MLP-AT1a receptor double knockout (DKO) mice were analyzed. MLPKO hearts showed marked chamber dilatation with cardiac fibrosis and reactivation of the fetal gene program. All of these changes were significantly milder in the DKO hearts. Impaired left ventricular (LV) contractility and filling were alleviated in DKO hearts. However, the impaired relaxation and downregulated expression of sarcoplasmic reticulum calcium-ATPase 2 were unchanged in DKO hearts.


CONCLUSIONS
The AT1a receptor is involved in progression of LV remodeling and deterioration of cardiac function in the hearts of MLPKO mice. These results suggest that blockade of the receptor is effective in preventing progression of heart failure in dilated cardiomyopathy.
Yamamoto
Rie
R
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Japan.
Akazawa
Hiroshi
H
Ito
Kaoru
K
Toko
Haruhiro
H
Sano
Masanori
M
Yasuda
Noritaka
N
Qin
Yingjie
Y
Kudo
Yoko
Y
Sugaya
Takeshi
T
Chien
Kenneth R
KR
Komuro
Issei
I
D000818:Animals; D002311:Cardiomyopathy, Dilated; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology*; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D020257:Ventricular Remodeling
D060588:LIM Domain Proteins; D009124:Muscle Proteins; D044140:Receptor, Angiotensin, Type 1; C090114:cysteine and glycine-rich protein 3