| Objective: Hypertensive left ventricular hypertrophy(LVH) serves as a high risk factor to cardiovascular events. Recently research on hypertensive left ventricular remodeling has involved complicated cellular and molecular mechanism such as inflammation, hyperplasia and apoptosis. Activation of renin-angiotensin-aldosterone system(RAAS) as a significant hormone factor contributes to the induction of LVH. Many experiments on animals have identified that RAAS induces prominently inflammatory damage on heart. Recently it was noted that the expression of a human homologue of Drosophila Toll, a proximal innate immunity transmemebrane signaling protein in the fly, now termed human Toll-like receptor 4(TLR4), appeared to be relatively high in the heart. TLR4 is one member of Toll family, which proved to provide a link between innate immunity and adaptive immunity. In normal murine, rat, and human myocardium, TLR4 expression was diffuse, and presumably cytoplasmic in cardiac myocytes. However, in remodeling murine myocardium remote from sites of ischemic injury and in heart tissue from patients with idiopathic dilated cardiomypathy, focal areas of intense TLR4 staining were observed in juxtaposed regions of two or more adjacent mocytes, this staining was not observed in control myocardium. Increased expression and signaling by TLR4, and perhaps other Toll homologues, may contribute to the activation of innate immunity and inflammatory reaction in injured myocardium. Therefore we presumed that TLR4 was involved in the initiation and development of hypertensive LVH by providing essential signals that permit a cascade of inflammatory response. TLR4 has been shown to induce activation of NFκB, so in this study, in addition to observation of the structure, function and myocardial fibrosis of left ventricle, we characterize the expression of TLR4 and NFκB in the left ventricular myocyte of hypertensive Goldblatt rats in order to preliminarily test our hypothesis.Methods: Sixteen male Sprague-Dawley rats enrolled were randomized to hypertensive group and contral group. Six sham-operated rats served as control group, and the Goldblatt model of renovascular hypertension was induced in the other ten rats. The echocardiogram was applied to observe the structure and function of left ventricle, and the tail cuff blood pressure was measured every week. At week six after the operation, all animals were killed and samples were collected. TLR4 and NFκB were detected in cardiomyocytes of Goldblatt rats and SD rats by immunohistochemistry. Victoria blue-Ponceau staining of cardiac collagen evaluated myocardial fibrosis and echocardiogram demonstrated left ventricular structure and function. Results:⑴Predominantly sarcolemmal staining was observed in cardiac muscle sections from hearts of hypertensive animals, especially focal areas of intense TLR4 staining were found in juxtaposed regions of two or more adjacent myocytes; However in cardiac myocytes of control animals, TLR4 expression was diffuse and presumably cytoplasmic. ⑵Immunohistochemical analysis demonstrate that the expression of TLR4 and NFκB enhanced in the hypertrophic cardiomyocytes from Goldblatt rats(p<0.01)and there is highly positive correlation between the two proteins (r=0.824,p<0.01). ⑶ Considerable correlation is found between blood pressure,LVMI,CVF,PVCA,EF and the expression of TLR4 in myocytes.Conclusions: The expression of TLR4 and NFκB enhanced in the hypertrophic cardiomyocytes in Goldblatt rats. The results provide evidence for a link between the immune receptor TLR4 and left ventricular hypertrophy.
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