Left ventricular hypertrophy induced by abdominal aortic banding and its prevention by angiotensin receptor blocker telmisartan—a proteomic analysis

Abstract

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.

Pulmonary Effects of Chronic Elevation in Microvascular Pressure Differ Between Hypertension and Myocardial Infarct Induced Heart Failure

“…These results suggest that the underlying mechanism behind pulmonary remodelling in CHF is regulated by more than chronic Pmv elevation alone. Previous studies utilising banding of the abdominal aorta in the rat as a model for CHF have similarly reported early increases in RV and LV weight and LVEDP, with only small changes in total lung weight up to eight weeks post-banding [17][18][19][20][21]. Between eight and 12 weeks a shift to approximately 40-97% increase in total lung weight is reported [7,[21][22][23][24][25][26].…”

Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium

“…Melting curves were performed for each reaction at the conclusion of the cycling parameters from 60°to 95°C. Fold changes in gene expression were calculated by using the ⌬⌬ (⌬⌬CT) method (20).…”

“…These proteins were myosin 2, ATP synthase subunit delta (mitochondria), heat shock protein ␤7, and stress-70 protein (mitochondria). Several proteomics analyses have identified alterations in metabolic proteins, heat shock proteins, and cell structure proteins as having important roles in modulating the effects of hypertrophy (19,20). Heat shock proteins are cardiac chaperones that increase during the development of cardiac hypertrophy.…”

“…We have demonstrated that changes in cardiomyocyte viability, lack of adaptive capillary growth, fibrosis, and response to metabolic stress are differentially regulated in LV-AOB and RV-PAB (11,13,16,20). However, the mechanisms involved in the compensated phase of LV-AOB and RV-PAB have yet to be clearly elucidated.…”

Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats

“…Valsartan, as an angiotensin receptor blocker, can be used to prevent or reverse cardiac hypertrophy, caused by multiple factors, via multiple signaling pathways [13,14,15,16,17,18]. In this study, we aimed to investigate whether the signaling pathway of Dyrk1A-ASF-CaMKIIδ was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats.…”