| Backgroud and Objectives:Collagen deposition in extracellular matrix, myocardial fibrosis, as well as the reconstruction of left ventricualr(LV) geometry occurred in the development of hypertensive LV dysfunction.Our previous study have found the association of left ventricular dysfunction with myocardial fibrosis and multidimensional deformation in spontaneously hypertensive rats(SHR), but the relationship between global or regional LV function and Galectin-3 and Brain natriuretic peptide(BNP) in myocardium is not clear unstood. This study is to investigate the expression of Galectin-3 and BNP in SHR in myocardium with aging, and their association with decreased LVEF and impaired LV multidimensional strain in SHR.Methods:Based on the previous study, SHR and WKY rats were randomly divided into several groups, 5-8 for each group, they were observed about 4-8 weeks interval, experiments were performed at different weeks(from 12 to 102 weeks). According to the age, left ventricular strain and global function, the rats were divided into 4 groups(12-22 w, 24-36 w, 45-66 w, 75-102w). Observation indexes: â‘ Echocardiographic measurements included relative wall thickness(RWT) and left ventricular mass index(LVMI), left ventricular ejection fraction(LVEF) and Fractional shortening(FS); â‘¡2-dimensional strain echocardiography measurements included end-systolic LV longitudinal strain(SL), radial strain(SR) and circumferential strain(SC); â‘¢histological measurement included the expression of Galectin-3 and BNP, myocardial collagen volume fraction(CVF) and perivascular collagen area(PVCA); â‘£Linear correlation of left ventricular structure, function and systolic strain and Galectin-3, BNP and fibrosis index.Results: Included the previous study, there are 121 rats in the experiment(82 spontaneously hypertensive rats, 39 Wistar-Kyoto rats).(1) The left ventricular structure and function index: â‘ IVST and LVPWT of SHR increased with aging, while IVSTI and LVPWTI was significantly increased during the 75-102 week(p<0.05), and it is higher than the corresponding age in WKY group(p<0.05); LVMI increased with aging, which increased more significantly than the previous week is at 45-66 and 75-102 weeks(p<0.05), it is higher than that of the WKY group at 75-102 weeks(p<0.05), LAD increased significantly at 45-66 and 75-102 weeks; â‘¡ pump index: LVEF in SHR remained stable during 22-66 weeks, which did not appear to reduce until 75-102 weeks(p<0.05), LVEF in SHR is lowered than that of the WKY group at the same time(p<0.05);â‘¢2DSE index: SL of SHR appeared to decrease from 45 weeks(p<0.05), while SR and SC began to decrease after 75 weeks, compared with the WKY group the all strain of SHR decreased significantly after 75 weeks(p<0.05).(2) Histological indicators: â‘ Collagen fiber: CVF and PVCA increased with aging, CVF-endo and PVCA were significantly increased at 45-66 weeks(p<0.05), while CVF-epi appeared significantly increased at 75-102 weeks(p<0.05) and CVF-endo was significantly higher than CVF-epi at the same time(p<0.05); â‘¡Immunohisto-chemical indicators: There is small amount of expression of Galectin-3 in myocardial interstitial of SHR at 12 weeks, which increased with aging. Compared with the WKY group, we began to see the difference at 45-66 weeks, and the difference was more obvious after 75 weeks(p<0.05); There is a small amount of expression of BNP in myocardium of SHR at 12-22 weeks, which is also increased with aging, it increased significantly at 45-66 weeks, while we can see the only difference between the two groups after 75 weeks(p<0.05), the positive expression rate in SHR was significantly higher than that of WKY group at 75 weeks [SHR: 46.7%(7 /15) VS. WKY:22.3%(2/9), p<0.05].(3) Correlation of left ventricular structure, functional and histological indicators: â‘ Galectin-3 was obviously correlated with LVMI, CVF-endo, CVF-epi and PVCA,(r=0.69, r=0.79, r=0.80, r=0.70, all the p=0.00), it is negatively correlated with SC, SR, SL and LVEF(r=-0.56, r=-0.49, r=-0.43, r=-0.62, all the p=0.00). â‘¡ BNP was correlated with LVMI, CVF-endo, CVF-epi and PVCA(r=0.57, r=0.86, r=0.68, r=0.70, all the p=0.00), it is negatively correlated with LVEF and strain(r=-0.70, p=0.00, r=-0.40, p=0.04, r=-0.41, p=0.00, r=-0.50, p=0.00).Conclusions:1. Myocardial interstitial Galectin-3 increases progressively with aging in SHR, especially from the age of 45~66 weeks, indicating its association with the development of left ventricular remodeling, myocardial fibrosis, as well as the order of decreased multidimensional strain in the development of LV dysfunction;2. BNP may occur in myocardium of SHR and WKY after 24 weeks, while strong positive expression or significant increase begins after 75 weeks when adverse global LV dysfunction happened;3. Galectin-3 and BNP may exist in LV myocardium of SHR with aging, but the pathological increase of Galectin-3 appeares earlier, suggesting a closer relationship between Galectin-3 and the development of myocardial fibrosis and cardiac dysfunction. |
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