Allicin Improves Hepatic Fibrosis by Regulating Notch 1 Pathway

Aim: To discuss effects and mechanisms of allicin in hepatic fibrosis by vivo study. Materials and methods: Dividing 45 rats into 5 groups. Evaluating pathology and fibrosis by HE and Masson staining, measuring α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression by IHC assay and WB assay; LC 3B protein expression were evaluated by Immunofluorescence. Liver function were measured by Elisa assay. Results: With Allicin supplement, rats’ liver function, pathological and Collagen volume fraction were significantly improved with doses-dependent in liver tissues (P < 0.05, respectively); α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression were significantly suppressed with doses-dependent (P < 0.05, respectively); LC 3B protein expression was significantly increased with doses-dependent (P < 0.05, respectively). Conclusion: Allicin improved hepatic fibrosis by authophagy up regulation via regulation Notrch1/AKT/mTOR pathway by vivo study.

Speckle Tracking Echocardiography Verified the Efficacy of Qianyangyuyin Granules in Alleviating Left Ventricular Remodeling in a Hypertensive Rat Model

Background. Global longitudinal strain (GLS) can be assessed by speckle tracking echocardiography (STE) to express the degree of cardiac fibrosis. Qianyangyuyin (QYYY) granules can effectively improve GLS in hypertensive patients. Using a hypertensive rat model, we carried out speckle tracking echocardiography to validate the effect of QYYY in diminishing LV remodeling. Methods. We randomly divided 16 spontaneously hypertensive rats (SHRs) into SHR, SHR + valsartan (SHR + V), SHR + low-dose QYYY (SHR + QL), and SHR + high-dose QYYY (SHR + QH) groups, with four rats in each group. Another group of 4 Wistar-Kyoto (WKY) rats were selected into a normal control (WKY) group. At the 8th week, conventional echocardiographic parameters were measured by GE Vivid E95 ultrasound (12S probe, 10–12 MHz) and GLS by speckle tracking echocardiography with EchoPAC (version 203) software. HE and Masson’s trichrome staining were performed to detect the cardiomyocyte width and collagen volume fraction after rat sacrifice. Collagen I, α-SMA, S100A4, TGF-β, Smad 3, MYH6, and MYH7 were further analyzed by Western blot. Results. The absolute values of GLS significantly increased in the SHR + QH group compared to the SHR group, while the CVF and CW values significantly decreased. In addition, Collagen I, α-SMA, S100A4, TGF-β, Smad3, MYH7, and MYH7/MYH6 ratio remarkably reduced in the SHR + QH group. The value of GLS could be repetitively measured and positively correlated with the collagen volume fraction of the myocardium and the cardiomyocyte width of the left ventricular free wall. Conclusions. GLS is a reliable indicator to evaluate the therapeutic effect on left ventricular remodeling in hypertension. QYYY granules can inhibit the development of cardiac fibrosis in the hypertensive rat model.

The Effect of Telmisartan on Collagen Percentages by Picrosirius Staining in the Glomerular Renal Organ of 8% NaCl-Induced Rats

Excessive salt consumption is one of the hypertension and kidney disease factors, while telmisartan is one of antihypertensive drugs used in the therapy. Telmisartan not only blocks angiotensin receptor which leads to the decrease of blood pressure, but also activates peroxisome proliferator activated receptor gamma (PPAR-γ) and inhibits transforming growth expression factor of beta-1 (TGFβ-1). Whether telmisartan decreases the kidney collagen volume fraction of excessive NaCl-induced Wistar rats are studied in this experiment. Twenty five male Wistars 2.5-3 months of age and 100-150 g BW rats were used in this research. They were grouped into 5, each consists of 5 rats. Group I (G I) as first negative control did not receive NaCl and telmisartan. G II as second negative control received NaCl but not telmisartan. G III, IV and V received NaCl and telmisartan 3, 6 and 12 mg/kg BW. The treatments were given every day within 8 weeks. At the day of 56 all rats were sacrificed by mean of neck dislocation and operated to take the kidney. The collagen was stained by picrosirius red staining. Data were expressed as mean ± standard deviation. They were analyzed by parametric test (analysis of variance-ANOVA and paired samples t-test) or nonparametric test (Kruskal-Wallis). A value of p0.05 was considered statistically significant. The results showed that intraglomerular and extraglomerular collagen volume fraction were lower in telmisartan-treated Wistar rats group than negative control group (0.05p0.05). In conclusion, intraglomerular and extraglomerular collagen volume fraction were lower in 8% sodium chloride-induced and telmisartan-treated male Wistar rats than the items of negative control group.

Right ventricular fibrosis is associated with cardiac remodelling after pulmonary valve replacement

ObjectiveThe relationship between right ventricular (RV) fibrosis and right heart reverse remodelling following pulmonary valve replacement (PVR) has not been well studied in adults with repaired tetralogy of Fallot (rTOF). Our aims were to histologically quantify RV fibrosis and to explore the relationship between fibrosis severity and cardiac remodelling post-PVR.MethodsAdults with rTOF and pre-PVR cardiovascular (CMR) imaging were consented to procurement of RV muscle during PVR. Samples were stained with picrosirius red to quantify collagen volume fraction. Clinical data at baseline and at last follow-up were reviewed. Adverse cardiovascular outcomes included death, sustained arrhythmia and heart failure.ResultsFifty-three patients (male 58%, 38±11 years) were studied. Those with severe fibrosis (collagen volume fraction >11.0%, n=13) had longer aortic cross-clamp times at initial repair compared with the remainder of the population (50 vs 33 min, p=0.018) and increased RV mass:volume ratio pre-PVR (0.20 vs 0.18 g/mL, p=0.028). Post-PVR, the severe fibrosis group had increased indexed RV end-systolic volume index (RVESVi) (74 vs 66 mL/m2, p=0.044), decreased RVESVi change (Δ29 vs Δ45 mL/m2, p=0.005), increased RV mass (34 vs 25 g/m2, p=0.023) and larger right atrial (RA) area (21 vs 17 cm2, p=0.021). A trend towards increased heart failure events was observed in the severe fibrosis group (15% vs 0%, p=0.057).ConclusionsSevere RV fibrosis was associated with increased RVESVi, RV mass and RA area post-PVR in rTOF. Further study is required to define the impact of fibrosis and persistent right heart enlargement on clinical outcomes.

Netrin-1 plays a role in the effect of 10 weeks moderate exercise on myocardial fibrosis in rats

This study aimed to determine the effect of Netrin-1 and its receptor on acute myocardial infarction in rats after aerobic exercise.METHODS:Twenty-four rats were randomly divided into three groups: the sham group (n = 8); acute myocardial infarction model group (AMI)(n = 8); and aerobic exercise treatment after acute myocardial infarction group(ET) (n = 8). After 10 weeks, the levels of netrin-1, tumor necrosis factor alpha α(TNF-α), and interleukin 6(IL-6) in the serum were measured. The expression of matrix metalloproteinases 2 and 9(MMP2,9), and their inhibitor, tissue inhibitor of metalloproteinases 2(TIMP2), myocardial netrin-1, Deleted in colorectal cancer(DCC) receptor were evaluated. Histopathological were evaluated. The collagen volume fraction of myocardial tissues was also calculated.RESULTS:Compared to the sham group, the AMI group and ET groups showed increased levels of serum TNF-α, IL-6 and significantly reduced levels of netrin-1. Levels of TNF-α and IL-6 were significantly reduced in the ET group compared to the AMI group, whereas the level of netrin-1 was increased. The expression of myocardial MMP2,9 was significantly increased in the AMI group compared to the sham group, whereas that of myocardial netrin-1, inhibitor of TIMP2 and DCC receptor, was significantly reduced. Compared to AMI group, the ET group showed reduced expression of myocardial MMP2,9 proteins, whereas expression of myocardial netrin-1, inhibitor of TIMP2 and DCC receptor, was significantly increased. The collagen volume fraction of myocardial tissues was significantly increased in the AMI group and ET group compared to the sham group, with the greater increase being noted in the AMI group.CONCLUSIONS: Aerobic exercise could increase levels of serum netrin-1 myocardial netrin-1, and DCC receptor and reduced expression of myocardial MMP2,9 proteins, to improve the degree of fibrosis following myocardial infarction in rats.

Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats

The objective of this study was to investigate the effect a nonselective endothelin-1 (ET-1) receptor antagonist (bosentan) had on the acute myocardial remodeling process including left ventricular (LV) mast cells and matrix metalloproteinase (MMP) activity secondary to volume overload. Additionally, we investigated the overall functional outcome of preventative endothelin receptor antagonism during 14 days of chronic volume overload. LV tissue from sham-operated (Sham), untreated-fistula (Fist), and bosentan (100 mg·kg−1·day−1)-treated animals (Fist + Bos) was analyzed for mast cell density, MMP activity, and myocardial collagen volume fraction at 1 and 5 days after the creation of an aortocaval fistula. When compared with untreated fistulas, bosentan treatment prevented the marked increase in LV mast cell density at 1 day postfistula (3.1 ± 0.3 vs. 1.3 ± 0.3 LV mast cells/mm2, Fist vs. Fist + Bos, P ≤ 0.01). Additionally, the substantial increase in MMP-2 activation in the untreated fistula at 1 day was prevented following bosentan treatment (1.6 ± 0.3 vs. 0.9 ± 0.1 arbitrary activity units, Fist vs. Fist + Bos, P ≤ 0.01). The marked decrease in collagen volume fraction seen in the Fist group (1.4 ± 0.1 vs. 0.8 ± 0.1% myocardial tissue, Sham vs. Fist, P ≤ 0.01) was significantly attenuated following bosentan treatment at both the 1- and 5-day time points. Lastly, a 2-wk preventative treatment with bosentan resulted in significant attenuation of the increase in LV end-systolic and -diastolic volumes compared with those in untreated fistula hearts. In summary, nonselective ET-1 antagonism prevents the acute increases in cardiac mast cell density and MMP activation induced secondary to chronic volume overload. By preventing these events, ET-1 antagonism was efficacious in attenuating ventricular dilatation and limiting the development of structural and functional deficits in the first 2 wk of chronic volume overload. Accordingly, these results are the first to demonstrate that cardiac mast cells are responsive to the endogenous endothelin system in vivo. Another novel finding from this study is that chronic nonspecific endothelin antagonism may inadvertently potentiate ET-1-mediated signaling.

Modulation of cardiac mast cell-mediated extracellular matrix degradation by estrogen

There are fundamental differences between males and females with regard to susceptibility to heart disease. Although numerous animal models of heart failure have demonstrated that premenopausal females are afforded cardioprotection and, therefore, fare better in the face of cardiac disease than their male counterparts, many questions as to how this occurs still exist. Recently, we showed that 1) increased mast cell density is associated with adverse ventricular remodeling and 2) chemically induced mast cell degranulation using compound 48/80 resulted in remarkable changes in matrix metalloproteinase (MMP) activity, cardiac collagen structure, and cardiac diastolic function in normal male rats. With the known gender differences in cardiac disease in mind, we sought to examine the effects of chemically induced cardiac mast cell degranulation in isolated, blood-perfused hearts of intact female rats, ovariectomized female rats, and ovariectomized female rats treated with 17β-estradiol. In response to mast cell degranulation, no significant differences in cardiac function, MMP-2 activity, or collagen volume fraction were observed between intact female rats and ovariectomized female rats treated with estrogen. In the ovariectomized female group, a significant rightward shift in the left ventricular pressure-volume relation, accompanied by a marked 133% increase in active MMP-2 values over that in the intact female group, was noted after treatment with compound 48/80 ( P ≤ 0.05), along with a significant reduction in collagen volume fraction below control (0.46 ± 0.23 vs. 0.73 ± 0.13%, P ≤ 0.05). These findings indicate that estrogen's cardioprotective role can be partially mediated by its effects on cardiac mast cells, MMPs, and the extracellular matrix.