Left ventricular hypertrophy induced by abdominal aortic banding and its prevention by angiotensin receptor blocker telmisartan--a proteomic analysis.
Cardiac hypertrophy is frequently caused by pressure overload (i.e., high blood pressure or hypertension) and can lead to heart failure. The major objective of the present study was to investigate the proteomic changes in response to the development of left ventricular hypertrophy (LVH) induced by abdominal aortic banding (AB) and its prevention by antihypertensive treatment with angiotensin II receptor blocker (ARB) telmisartan. One week after AB and Sham surgery, rats were assigned into three groups: SHAM-control, aortic banding without treatment (AB-Ctrl) and aortic banding with telmisartan treatment (AB-Telmi; 5mg/kg/day for 8 weeks). Echocardiography, hemodynamics, and pathology were performed to assess LVH. Left ventricular myocardium was sampled. The analysis of proteomic proteins from myocardium was performed by two-dimensional gel electrophoresis and MALDI-TOF-MS. In AB-Ctrl, heart rate, systolic arterial blood pressure, diastolic blood pressure, left ventricular end systolic pressure, interventricular septal thickness at diastole, posterior wall thickness in diastole, heart weight (HW) and HW/body weight (BW) were increased, indicating that both hypertension and LVH developed. Telmisartan prevented hypertension and LVH. Concurrently, among numerous proteins, there were 17 that were differentially expressed among hypertrophic hearts, normal hearts, and the hearts where hypertrophic response was suppressed by ARB treatment. Primarily, proteins involved in cell structure, metabolism, stress and signal transduction exhibited up-regulations in LVH, providing cellular and molecular mechanism for hypertrophic development. These changes were prevented or greatly attenuated by telmisartan regimen. Interestingly, antioxidative-related heat shock protein 2 was detected neither in SHAM-Ctrl nor in AB-Ctrl, but in AB-Telmi. LVH is accompanied by series changes of protein expression. Both LVH and proteomic changes can be prevented by blockade of renin-angiotensin system with telmisartan. These protein alterations may constitute mechanistic pathways leading to hypertrophy development and experimental targets for novel therapeutic strategy.
Liu
Li
L
Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, China.
Wang
Wen
W
Meng
Xianmin
X
Gao
Jiuming
J
Wu
Haiying
H
Wang
Peihe
P
Wu
Weichun
W
Wang
Linlin
L
Ma
Liyuan
L
Zhang
Weiguo
W
D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000473:pathology; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure; D004452:Echocardiography / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional; D006333:Heart Failure / Q000209:etiology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000077333:Telmisartan
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan