scholarly journals Cardioprotection against Heart Failure by Shenfu Injection via TGF-β/Smads Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Jingyu Ni ◽  
Yang Shi ◽  
Lan Li ◽  
Jingrui Chen ◽  
Lingyan Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Structure And Function ◽  
Sprague Dawley ◽  
Shenfu Injection ◽  
Sprague Dawley Rats ◽  
And Function

Objective. To explore the potential cardioprotective mechanism of Shenfu injection (SFI) against heart failure (HF) by attenuating myocardial fibrosis and cardiac remodeling.Methods and Results. Four weeks after myocardial infarction (MI), adult male Sprague Dawley rats were randomized for 4-week treatment with Valsartan, SFI, or vehicle. Echocardiography and hemodynamics were applied to evaluate cardiac functions. Myocardia of coronary artery ligated (CAD) rats were observed to investigate changes in cardiac structure and function. Our findings suggest that treatment with SFI could inhibit progression of myocardial fibrosis and attenuate cardiac remodeling. In addition, SFI decreased expression of Smad2 and Smad3, while increasing the expression of Smad7 through regulation of TGF-β/Smads signaling pathway.Conclusion. Treatment with SFI in Sprague Dawley rats improves ventricular structure and function and reduces cardiac fibrosis by ameliorating TGF-β/Smads signaling pathway after ventricular remodeling.

scholarly journals Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5006
Author(s):  
Pema Raj ◽  
Karen Sayfee ◽  
Mihir Parikh ◽  
Liping Yu ◽  
Jeffrey Wigle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Additive Effects ◽  
Sprague Dawley ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Sprague Dawley Rats ◽  
And Function ◽  
Neutrophil Gelatinase

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.

Abstract 3880: GRK2 Inhibition Prevents Development Of Cardiac Insulin Resistance And Impaired Glucose Uptake In Post Ischemic Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michele Ciccarelli ◽  
Giuseppe Rengo ◽  
Kurt Chuprun ◽  
Gaetano Santulli ◽  
Bruno Trimarco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Uptake ◽  
Fluorescent Protein ◽  
Sprague Dawley ◽  
Myocardial Glucose Uptake ◽  
Akt Phosphorylation ◽  
Neonatal Cardiomyocytes ◽  
Sprague Dawley Rats ◽  
Green Fluorescent ◽  
And Function

The beta adrenergic receptor (βAR) kinase, GRK2, is upregulated and participates to the evolution of heart failure (HF) through downregulation and desensitization of βARs. Recent studies showed that this molecule affects insulin signaling and reduce glucose uptake in hepatocytes and adipocytes. We hypothesized that in HF, GRK2 reduces cardiac performance also through inhibition of cardiac glucose metabolism. In 12 week old Sprague/Dawley rats, we measured cardiac glucose uptake by PET 3 days, 3 and 6 weeks after myocardial infarction (MI). Function and cardiac dimensions were measured by echocardiography. We observed that glucose uptake was reduced in animal post-MI at 3 and 6 weeks respect to healthy animals (3 rd week: 1.3±0.22 vs 2.1±0.3; 6 th week: 1±0.1 vs 2.4±0.2, ml/min/g, p<0.05). No difference was observed in glucose uptake acutely after surgery. Echo showed cardiac dilation and reduced function at 6 weeks (LVD: 9.2± 0.3 vs 7.2± 0.4 mm; EF: 42%±1.1 vs 66%±2.2, p<0.05, Sham vs MI). To inhibit GRK2 in the heart during post-ischemic HF, we delivered the GRK2 inhibitor βARKct by adeno-associated type 6 virus (AAV6) to the left ventricle before induction of the MI. As a control we treated rats with AAV6 encoding for the green fluorescent protein (GFP). Cardiac dilation and function were preserved after 6 weeks post MI in AAV6 βARKct respect to AAV6GFP rats (LVD: 7.73 ±0.25 vs 9.9 ±0.8 mm; EF: 55%±2.25 vs 44%±2, p<0.05). Glucose uptake was better preserved in AAV6βARKct rats after 3 and 6 weeks post MI respect to AAV6GFP group (3rd week: 2.3±0.3 vs 1.2±0.2; 6th week: 1.8±0.2 vs 1.1±0.05, ml/min/g, p<0.05). Since Akt mediates most of the anabolic effects of insulin in cells, we evaluated the effects of GRK2 overexpression by adenovirus (ADGRK2) in neonatal cardiomyocytes (NRVMs) on Akt phosphorylation later on insulin stimulation (ins, 10 – 6 M). As control we induced overexpression of GFP by adenovirus (ADGFP). We observed reduced activation of Akt in presence of GRK2 overexpression as compared to the ADGFP treated cells (1.2±0.2- vs. 3.5±0.4- fold activation over basal, p<0.05). Our data show that post MI, impaired glucose extraction precedes development of HF, and that early GRK2 inhibition prevents impaired myocardial glucose uptake and HF development.

scholarly journals The protective effects of liguzinediol on congestive heart failure induced by myocardial infarction and its relative mechanism

2020 ◽  
Author(s):  
Qi Chen ◽  
Dini Zhang ◽  
Yunhui Bi ◽  
Weiwei Zhang ◽  
Yuhan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Myocardial Cell ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cardiac Functions ◽  
Tgf Β1

Abstract Background : Heart failure (HF) is one of the most common causes of cardiovascular diseases in the world. Currently, the drugs used to treat HF in the clinic may cause serious side effects. Liguzinediol, 2, 5-dimethyl-3, 6-dimethyl-pyrazine, is a compound synthesized after the structural modification of ligustrazine (one active ingredient of Szechwan Lovage Rhizome ). We aimed to observe the effects of liguzinediol on preventing HF and explore the related mechanisms. Methods : The ligation of left anterior descending coronary artery was operated to established the myocardial infarction (MI) model in Sprague–Dawley rats. Cardiac functions were recorded by echocardiography and hemodynamics. The changes in the Renin-Angiotensin-Aldosterone System (RAAS), inflammation, and oxidative stress were detected by radioimmunoassay and Elisa kits. Western blot and real-time PCR were applied to determine the expressions of the TGF-β1/Smads pathway. Results : Firstly, liguzinediol enhanced the systolic and diastolic functions of the heart in MI rats. Liguzinediol improved ventricular remodeling by reducing myocardial cell necrosis, as well as reducing collagen deposition and myocardial fibrosis. Then, liguzinediol suppressed the activation of RAAS, inhibited the synthesis of pro-inflammation factors, and reduced oxidative stress. In the end, liguzinediol also down-regulated the expressions of the TGF-β1/Smads pathway. Conclusions : Liguzinediol could alleviate HF caused by MI in rats, and the protective effect was associated with the regulation of the TGF-β1/Smads pathway.

Abstract 193: Multiple Prior Live Births Are Associated With Cardiac Remodeling and Heart Failure in Women

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Amy Sarma ◽  
Samantha Paniagua ◽  
Elizabeth Liu ◽  
Emily Lau ◽  
Martin Larson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Structure And Function ◽  
Cardiovascular Health Study ◽  
Cardiac Structure ◽  
Live Births ◽  
Nulliparous Women ◽  
Increased Risk ◽  
Cardiac Structure And Function ◽  
And Function

Introduction: Greater parity has been associated with increased risk of cardiovascular disease, though effects on cardiac remodeling and heart failure risk remain unclear. Hypothesis: We hypothesized that multiple prior live births are associated with (1) structural and functional cardiac remodeling and (2) risk of future heart failure. Methods: We examined the association of number of live births and echocardiographic measures of cardiac structure and function in women participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure (HFpEF, HFrEF) using Cox models in a pooled analysis of n=10,431 participants of FHS, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis. Results: Among n=3931 FHS participants (mean age 48 ± 13 years), higher number of live births was associated with worse LV fractional shortening (multivariable β -1.11 (0.31), p= 0.0005 in ≥ 5 live births vs nulliparous women, p trend= 0.02, Figure ). In addition, greater parity was associated with worse cardiac mechanics including global circumferential strain and longitudinal and radial dyssynchrony (p< 0.01 for all comparing ≥ 5 live births vs nulliparity). Over a mean follow-up of 11.7 ± 3.2 years, 298 HFpEF and 225 HFrEF events occurred. Women with ≥5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19-3.12, p=0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37-0.91, p=0.02, p trend= 0.04). Conclusions: Greater number of live births are associated with worse cardiac structure and function, as well as increased risk of incident HFrEF. Further studies are needed to better understand mechanisms by which repeated pregnancies portend adverse cardiovascular risk.

scholarly journals Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Junyan Wang ◽  
Bo Deng ◽  
Qing Liu ◽  
Yusheng Huang ◽  
Weitao Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Ventricular Remodeling ◽  
Pressure Overload ◽  
Mixed Lineage Kinase ◽  
Ventricular Cells ◽  
Mixed Lineage Kinase 3

Abstract Chronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and is a severe health issue faced by the elderly population. Mixed lineage kinase 3 (MLK3), a member of MAP3K family, is associated with aging, inflammation, oxidative stress, and related diseases, such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function in myocardial fibrosis is unknown. To investigate the role of MLK3 in myocardial fibrosis, we inhibited the expression of MLK3, and examined cardiac function and remodeling in TAC mice. In addition, we assessed the expression of MLK3 protein in ventricular cells and its downstream associated protein. We found that MLK3 mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation and that pyroptosis causes myocardial fibrosis in the early stages of CHF. Similarly, MLK3 mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of CHF. We also found that promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. These results suggest the pyroptosis and ferroptosis induced by MLK3 signaling in cardiomyocytes are essential for adverse myocardial fibrosis, in response to pressure overload. Furthermore, miR-351, which has a protective effect on ventricular remodeling in heart failure caused by pressure overload, may be a key target for the regulation of MLK3.

scholarly journals Effect of different sweeteners on the oral microbiota and immune system of Sprague Dawley rats

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xi Cheng ◽  
Xiurong Guo ◽  
Feihong Huang ◽  
Hui Lei ◽  
Quan Zhou ◽  
...  
Keyword(s):  
Immune System ◽  
High Throughput Sequencing ◽  
Pure Water ◽  
Structure And Function ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
And Function

AbstractSucrose, xylose, and saccharin are commonly used beverage additives and long-term consumption of these compounds inevitably affects the oral immune system and the composition of oral microbiomes. In this study, we used 24 Sprague Dawley rats divided into four groups, i.e., sucrose, saccharin, xylose, or pure water treated over an eight week period to evaluate any changes in the composition, community structure, and function of the oral microbiomes. At the end of the treatment period, we collected oral microbiome samples from each animal and subjected them to high-throughput sequencing. We also used ELISA to determine the concentration of salivary immunoglobulin in these rats to reveal the effect of sweetener on the oral immune system. Sequencing results demonstrated that Firmicutes and Proteobacteria, remained the predominant phyla, but we found that the oral microbial diversity of rats drinking sucrose water was significantly higher than that of the other groups. Our results indicate that drinking water supplemented with sweeteners may influence oral immunity as well as the composition, metabolic function, and diversity of the oral microbiota, thereby disrupting the oral microbiome.

scholarly journals Fat cardiomyopathy in patients with severe degree of obesity. Case report

2021 ◽  
Vol 93 (9) ◽  
pp. 1073-1077
Author(s):  
Sofia V. Miklishanskaya ◽  
Olga V. Stukalova ◽  
Lilia V. Solomasova ◽  
Nikolai A. Mazur
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Systolic Heart Failure ◽  
Tissue Doppler ◽  
Structure And Function ◽  
Severe Degree ◽  
And Function

Currently, the world is constantly increasing the number of people with obesity. As was shown by the Framingham study, obesity is a risk factor for many cardiovascular diseases. The effect of obesity on the structure and function of the heart is manifested in the form of cardiac remodeling, the effect on energy metabolism in the heart and infiltration of both myocardium with lipids, and an increase in the accumulation of adipose tissue in the pericardium, imbalance of adipokines and activation of inflammatory markers. Cardiac remodeling occurs primarily due to thickening of the left ventricle (LV) walls and an increase in the LV myocardium mass. Systolic dysfunction of the heart is less common in obese individuals compared with diastolic dysfunction. However, more modern methods (tissue Doppler, visualization of the deformation of the chambers of the heart strain imaging) reveal a subclinical decrease in systolic function in people with obesity. It is not fully known whether obesity is associated with systolic dysfunction, regardless of other risk factors. In any case, it has been proven that heart failure in people with obesity can develop independently of other risk factors. As an illustration, we give an example when the presence of obesity and concomitant pathology (arterial hypertension, diabetes) led to the development of systolic dysfunction with a decrease in the LV ejection fraction to 35% (fat cardiopathy), which show the potential for the influence of both obesity itself and in combination with concomitant diseases to lead to severe systolic heart failure.

scholarly journals Azadirachta excelsa Improves Renal Morphology and Function in Streptozotocin Induced-Diabetic Sprague Dawley Rats

2020 ◽  
Vol 17 (12) ◽  
pp. 1307-1320
Author(s):  
Nur Syimal Aain AZMI ◽  
Nooraain HASHIM ◽  
Nurdiana SAMSULRIZAL ◽  
Noor Syaffinaz NOOR ◽  
Mohamad ZIN
Keyword(s):  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Structure And Function ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Standard Drug ◽  
Sprague Dawley Rats ◽  
Renal Morphology ◽  
And Function

Long term diabetes mellitus (DM) is associated with serious complications such as nephropathy. Previous studies revealed the ability of A. excelsa leaf extract treatment to reduce fasting blood glucose (FBG) in streptozotocin (STZ)-induced diabetic rats. The aim of this study was to determine the effect of A. excelsa extract in delaying the progression of diabetic nephropathy by evaluating the kidney structure and function. The effects were compared with 2 positive controls, which were metformin (standard drug) and quercetin (plant active compound). Induction of diabetic conditions was conducted by the intraperitoneal (IP) injection of STZ (60 mg/kg bwt) in male Sprague Dawley rats. The experimental animals were grouped into: 1) normal control (NC, saline); 2) diabetic control (DC, saline); 3) metformin-treated diabetic rats (DMET, 1000 mg/kg bwt); 4) quercetin-treated diabetic rats (DQ, 40 mg/kg bwt), and 5) A. excelsa-treated diabetic rats (DAE, 250 mg/kg bwt). All treatments were given once daily for 8 weeks through oral gavage. The inter-relation between the changes in the fasting blood glucose and kidney oxidative stress, structure, and function was evaluated. The results showed a significant increase (p < 0.05) of MDA and SOD level and a decrease (p < 0.05) of GPx levels, plus distortion of renal morphology among the DC and DMET groups. Meanwhile, both DQ and DAE groups showed significant reduction (p < 0.05) of MDA levels and elevation (p < 0.05) of SOD and GPx levels. The quercetin and A. excelsa treatments also improved the kidney function parameters and morphological changes of the diabetic rats. These findings indicate that quercetin and A. excelsa possess renal therapeutic effects.

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