Differential protein expression in hypertrophic heart with and without hypertension in spontaneously hypertensive rats

Abstract

Although cardiac hypertrophy in hypertension has been well recognized, the molecular mechanisms for the development of hypertrophy are still largely unknown. In this study, the protein expression profiles of left ventricular myocardia in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at different ages were analyzed using 2-DE in combination with MALDI-TOF/TOF MS/MS. The results showed that 20 proteins were modulated in the hypertrophic myocardium. Out of these modulated proteins, 13 proteins presented significant changes in SHR at an early stage prior to the development of sustained hypertension, while the changes of the other 7 protein expressions occurred only at a late stage in SHR when the blood pressure was significantly elevated, and were largely reversible by treatment with rennin-angiotensin-aldosterone system inhibitors losartan or enalapril. These data demonstrate that the changes in energy metabolism in the hypertrophied heart favor an increase in glycolysis and a decrease in oxidation of fatty acid and glucose, which occur at an early stage in SHR without hypertension. Our results also provide evidence to support the hypothesis that oxidative stress plays an important role in the development of hypertensive cardiac hypertrophy.

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

“…Unlike other studies where LVH was developed first and then treated, the LVH was not developed in the AB-Telmi group at the time when treatment started, so the proteomic changes in ABTelmi group must have been caused by talmisartan. Four proteins identified were cellular energy and metabolism related, e.g., L-3-hydroxyacyl-coenzyme A dehydrogenase, a protein related to fatty acid oxidation was down-regulated; whereas glyceraldehyde-3-phosphate dehydrogenase, an important enzyme in glycolysis was up-regulated in the hypertrophied hearts, which is consistent with energy metabolism pattern of the embryo heart [4] or the data from spontaneously hypertensive rats [10]. As previously reported, the heart utilizes ATP generated by fatty acid and glucose oxidation.…”

“…↑ represents protein appeared in AB-Telmi group only *P<0.05 vs. AB-Ctrl **P<0.01 vs. AB-Ctrl hypertrophy, the pathway of fatty acid oxidation is impaired, thus glycolysis has to increase [7,10]. Telmisartan promoted the expression of proteins related to fatty acid oxidation and suppressed the expression of those embryonic proteins related to glycolysis.…”

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

“…Examples include a study by Jin et al [58] that examined protein expression changes occurring during development of left ventricular hypertrophy, using 2D gel electrophoresis in combination with matrix assisted laser desorption/ionization – time of flight tandem mass spectrometry (MALDI-TOF/TOF MS/MS) in left ventricular myocardium from SHR and normotensive Wistar Kyoto (WKY) rats. They reported 13 proteins that were differentially expressed in the SHR before the onset of hypertension.…”

Proteomic analysis of left ventricular diastolic dysfunction hearts in renovascular hypertensive rats

“…Adequate energy supplies and the mechanisms to regenerate them must be present for this process to occur at a sufficient rate and extent, any modification of energy supplies and alteration of these steps can surely alter the myocardial diastolic function. By 2-DE analysis, changes in the expression of a variety of proteins involved in energy metabolism during hypertrophy have been described elsewhere [12,28]. The expressions of pyruvate dehydrogenase complex E2 (spot 2), alpha-enolase (spot 6) and triosephosphate isomerase (spot 8), three important enzymes in glycolysis, were found to be significantly upregulated in the present study, which indicates an increased glycolysis processes in diastolic dysfunction and consistent with the fact that the energy substrate switch away from fatty acid utilization to glycolysis in the pathological hypertrophied heart.…”

“…Differentially expressed cardiomyocyte proteins were defined as those proteins that consistently changed in abundance in six independent gels. After then, protein spots were manually excised from the gels, destained, and subjected to in-gel digestion in digestion solution (12.5 μg/mL trypsin in 25 mM NH 4 HCO 3 ) using the method described elsewhere [12].…”