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Objective To investigate the effects of swimming exercise training on left ventricular (LV)remodeling and its possible mechanism in spontaneous hypertensive rats (SHR).Methods Twenty eightweek-old male SHRs were divided into SHR control (SC) group and SHR exercise training (ST) group,with 10 rats in each group.Ten eight-week-old male Wistar rats were used as normal control (WC) group.The ST group was subject to 60-min moderate swimming exercise without loading once daily,6 times a week,for a total of 12 weeks; while the SC and WC group had no special intervention.The blood pressure was examined once weekly.After 12 weeks,the norepinephrine (NE)and serum angiotonin Ⅱ (ANG Ⅱ) levels were determined by ELISA.The LV hypertrophy was assessed by analysing the ratio of LV weights to body weights (LVW/BW) and cardiomyocyte diameter.The collagen deposited in LV was detected by sirius red staining.The expressions of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) in LV were determined by semi-quantitative real time-polymerase chain reaction (RT-PCR) and Western blotting.Results After 12 weeks,the blood pressure,serum NE and ANG Ⅱ levels,LVW/BW ratio,cardiomyocyte diameter and collagen volume fraction (CVF) increased significantly in SC group compared with WC group; while those in ST group decreased significantly.In addition,in ST group the mRNA and protein expressions of TNF-α,IL-6,IL-1 βand TGF-β1 also decreased significantly.Conclusions The swimming exercise could reduce the blood pressure of SHR and improve LV remodeling.This effect was mediated not only by improving the hemodynamics,but also by decreasing sympathetic nerve and renin-angiotensin system (RAS) activities,decreasing the gene expressions of cytokines.The swimming exercise may be an effective strategy for improving LV remodeling in hypertension.
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<p><b>BACKGROUND</b>Hepatocyte growth factor (HGF) inhibits the development of pulmonary artery hypertension (PAH) by reducing pulmonary artery pressure and right ventricle (RV) hypertrophy. However, whether HGF can prevent RV remodeling via inhibiting apoptosis in RV cardiomyocytes and decreasing neurohormonal activation remains unknown.</p><p><b>METHODS</b>The PAH and subsequent RV remodeling in rats were induced by subcutaneous injection of monocrotaline (MCT). The PAH rats were transfected with adenovirus carrying HGF (Ad-HGF) via intratracheal instillation. Three weeks after transfection, the hemodynamics indexes were measured, serum levels for angiotonin II (ANG II) and brain natriuretic peptide (BNP) were determined by ELISA. Histological analysis was used to assess the RV hypertrophy and fibrosis. The cardiomyocyte apoptosis in RV was assayed by TUNEL staining. The mRNA expression of BNP, angiotensin-converting enzyme (ACE), Bax and Bcl-2 in RV was determined by reverse transcriptase polymerase chain reaction (RT-PCR), the protein expression of transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α in RV was determined by Western blotting.</p><p><b>RESULTS</b>HGF treatment significantly decreased the mean PAH, RV systolic pressure, serum ANG II and BNP levels. HGF treatment also significantly decreased the RV hypertrophy, collagen deposition, and the number of apoptotic cardiomyocytes. Moreover, HGF treatmemt significantly decreased the expression of BNP, ACE, Bax, TGF-β1, and TNF-α, while it significantly increased the expression of Bcl-2.</p><p><b>CONCLUSIONS</b>Gene transfer of HGF decreases MCT-induced PAH and improves RV remodeling. This effect is mediated not only by improving the hemodynamics but also by decreasing neurohormonal activation and inhibiting cardiomyocytes apoptosis. HGF gene treatment may be an effective strategy for improving RV remodeling in MCT-induced PAH.</p>
Subject(s)
Animals , Humans , Male , Rats , Apoptosis , Genetics , Physiology , Hepatocyte Growth Factor , Genetics , Physiology , Therapeutic Uses , Hypertension, Pulmonary , Metabolism , Therapeutics , Rats, Sprague-Dawley , Ventricular Remodeling , Genetics , PhysiologyABSTRACT
This study examined the change of p16(INK4a) and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts (hIGF-1-myoblasts) were injected into hind limb muscles of 18 post-infraction rats (experimental group). Primary-myoblasts were injected into 18 post-infraction rats (control group) and 12 non-infarction rats (sham group). Expression of p16(INK4a) and PCNA protein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the sham group, the percentage of p16(INK4a) and PCNA positive cells reached a peak after 1 week in the control group and the experimental group (P0.05). ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group (P<0.01). The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group (P<0.01). The hIGF-1 protein in serum and myocardium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p16(INK4a) and PCNA protein (r=-0.323, P<0.05; r=0.647, P<0.01). It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16(INK4a) protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.
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ObjectiveTo explore the effects of recombinant human growth hormone(rhGH)on myocardial inflammatory cytokine expression and heart function in rats with acute myocardial infarction (AMI). MethodsRats with AMI induced by left anterior descending coronary branch ligation were randomized to rhGH and control groups compared with sham-operated group. The effects of 4 weeks of therapy with GH starting 24 hours after myocardial infarction on myocardial cytokines expression and heart function were studied. Myocardial inflammation was examined by analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function. ResultsThe levels of TNF-α, IL-1β, IL-6 and IL-10 in the infarcted and non-infarcted region of control group were markedly elevated compared to sham-operated group (all P＜0.05). After 4 weeks therapy, rhGH reduced the expression of TNF -α, IL-1β, IL-6 and increased IL-10 expression in the infarcted and non-infarcted region of rhGH group compared to control group (all P＜0. 05 ). Echocardiography showed that rhGH markedly improved left heart function (P＜0. 05 ). ConclusionsEarly rhGH treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One of immunopharmacologic mechanisms underlying the beneficial effects of rhGH on heart function improvement may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.