TY - JOUR
T1 - Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy
AU - von Lueder, Thomas G
AU - Wang, Bing Hui
AU - Kompa, Andrew Richard
AU - Huang, Li
AU - Webb, Randy
AU - Jordaan, Pierre
AU - Atar, Dan
AU - Krum, Henry
PY - 2015
Y1 - 2015
N2 - Background-Angiotensin-receptor neprilysin inhibitors (ARNi), beyond blocking angiotensin II (AngII)-signalling, augment natriuretic peptides by inhibiting their breakdown
by neprilysin (NEP). The myocardial effects of ARNi have been little studied until recently. We hypothesized that LCZ696 attenuates left ventricular (LV) remodeling after experimental myocardial infarction (MI), and that this may be contributed to by inhibition of hypertrophy and fibrosis in cardiac cells.
Methods and Results?One week after MI, adult male Sprague-Dawley rats were randomized to treatment for four weeks with LCZ696 (68 mg/kg body weight PO; MI-ARNi,
n=11) or vehicle (MI-Vhc, n=6). Five weeks after MI, MI-ARNi versus MI-Vhc demonstrated lower LV end-diastolic diameter (LVEDD, by echocardiography; 9.7?0.2 vs
10.5?0.3 mm), higher LV ejection fraction (LVEF, 60?2 vs 47?5 ), diastolic wall strain (0.23?0.02 vs 0.13?0.02), and circular strain (CS, -9.8?0.5 vs -7.3?0.5 ; all P
AB - Background-Angiotensin-receptor neprilysin inhibitors (ARNi), beyond blocking angiotensin II (AngII)-signalling, augment natriuretic peptides by inhibiting their breakdown
by neprilysin (NEP). The myocardial effects of ARNi have been little studied until recently. We hypothesized that LCZ696 attenuates left ventricular (LV) remodeling after experimental myocardial infarction (MI), and that this may be contributed to by inhibition of hypertrophy and fibrosis in cardiac cells.
Methods and Results?One week after MI, adult male Sprague-Dawley rats were randomized to treatment for four weeks with LCZ696 (68 mg/kg body weight PO; MI-ARNi,
n=11) or vehicle (MI-Vhc, n=6). Five weeks after MI, MI-ARNi versus MI-Vhc demonstrated lower LV end-diastolic diameter (LVEDD, by echocardiography; 9.7?0.2 vs
10.5?0.3 mm), higher LV ejection fraction (LVEF, 60?2 vs 47?5 ), diastolic wall strain (0.23?0.02 vs 0.13?0.02), and circular strain (CS, -9.8?0.5 vs -7.3?0.5 ; all P
UR - http://circheartfailure.ahajournals.org/content/8/1/71.full.pdf+html
U2 - 10.1161/CIRCHEARTFAILURE.114.001785
DO - 10.1161/CIRCHEARTFAILURE.114.001785
M3 - Article
SN - 1941-3289
VL - 8
SP - 71
EP - 78
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 1
ER -