scholarly journals Neuregulin-1 Promotes Myocardial Angiogenesis in the Rat Model of Diabetic Cardiomyopathy

2018 ◽  
Vol 46 (6) ◽  
pp. 2325-2334 ◽  
Author(s):  
Chun Gui ◽  
Zhi-yu  Zeng ◽  
Qi Chen ◽  
Ya-wei Luo ◽  
Lang Li ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Treatment Group ◽  
Cardiac Function ◽  
Left Ventricular Function ◽  
Diabetic Cardiomyopathy ◽  
Rat Model ◽  
Capillary Density ◽  
Left Ventricular ◽  
Control Group ◽  
Neuregulin 1

Background/Aims: Microvascular insufficiency takes a critical role in the development of diabetic cardiomyopathy (DCM). So this study was designed to investigate the effects of Neuregulin-1 (NRG-1) treatment on myocardial angiogenesis and the changes of VEGF/Flk1 and Ang-1/Tie-2 signaling in the rat model of DCM. Methods: Diabetic rats were induced by a single intraperitoneal injection of Streptozotocin. 12 weeks after the diabetes induction, the rats with NRG-1 treatment were treated with tail vein injection of NRG-1 at the dose of 10µg/kg/d for consecutive 10 days. Cardiac function was assessed using catheter MPA cardiac function analysis system. Myocardial blood flow (MBF) was assessed with stable-isotope labeled microspheres. Capillary density was measured by CD31 immunohistochemistry. The protein expression and receptors phosphorylation were assessed using western blot. Results: Left ventricular function, capillary density and MBF were significantly reduced in DCM group when compared with those in the control group (P< 0.01, P< 0.01 and P< 0.05 respectively). Left ventricular function and capillary density were significantly increased in NRG-1 treatment group when compared with those in the DCM group (P< 0.05 and P< 0.05 respectively). The expression of VEGF and Ang-1 and the phosphorylation of Flk1 and Tie-1 were significantly decreased in DCM group as compared with those in the control group. However, those in the NRG-1 treatment group were significantly increased as compared with those in the DCM group. In vitro, NRG-1 treatment increased significantly the expression of VEGF and Ang-1 in human coronary artery smooth muscle cells. Conclusions: NRG-1 can increase the myocardial angiogenesis of DCM, probably via the direct effects of NRG-1 and via the increasing expression of VEGF and Ang-1. These findings may contribute to developing a novel approach to reverse the impaired angiogenic responses in diabetes or coronary artery disease.

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

scholarly journals Cardioprotective Effect of Decorin in Type 2 Diabetes

2020 ◽  
Vol 11 ◽  
Author(s):  
Fuqiong Chen ◽  
Jinsheng Lai ◽  
Yanfang Zhu ◽  
Mengying He ◽  
Huiying Hou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Diabetic Cardiomyopathy ◽  
Treated Group ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Cardiac Inflammation

Cardiomyopathy is the leading cause of increased mortality in diabetes. In the present study, we investigated the effects of decorin (DCN) gene therapy on left ventricular function, cardiac inflammation and fibrosis in type 2 diabetes. Type 2 diabetes was induced in male Wistar rats by high fat diet (HFD, 60% of calories as fat) and STZ (20 mg/kg, intraperitoneal). Diabetic rats were divided into (n=6 for each group) the control group, the GFP-treated group and the DCN-treated group, received intravenous injection of saline solution, recombinant adeno-associated viral (rAAV)-GFP, and rAAV-DCN, respectively. We evaluated cardiac inflammation, fibrosis, left ventricular function at 6 months after gene delivery. Results turned out that rAAV-DCN treatment attenuated diabetic cardiomyopathy with improved LV function compared with control animals, which might be related to the reduced cardiac inflammation and fibrosis. These protective effects were associated with TGFβ1 pathway (ERK1/2 and smad-2) and NF-κB pathway, which may due to the decreased activation level of IGF-IR, increased expression of PKC-α and Hsp70. In conclusion, our results show that rAAV-mediated DCN therapy may be beneficial in the treatment of Diabetic Cardiomyopathy.

Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia

2006 ◽  
Vol 101 (4) ◽  
pp. 1091-1096 ◽  
Author(s):  
Xiangshao Fang ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Lei Huang ◽  
Yun-Te Chang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Coronary Artery ◽  
Cardiopulmonary Resuscitation ◽  
Myocardial Ischemia ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Chronic Myocardial Ischemia

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.

Decreased left ventricular function, myocarditis, and coronary arteriolar medial thickening following monocrotaline administration in adult rats

2007 ◽  
Vol 103 (1) ◽  
pp. 287-295 ◽  
Author(s):  
F. Akhavein ◽  
E. Jean St.-Michel ◽  
E. Seifert ◽  
C. V. Rohlicek
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Cardiac Function ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Pulmonary Artery Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Artery Pressure ◽  
Medial Thickening

Decreased right as well as left ventricular function can be associated with pulmonary hypertension (PH). Numerous investigations have examined cardiac function following induction of pulmonary hypertension with monocrotaline (MCT) assuming that MCT has no direct cardiac effect. We tested this assumption by examining left ventricular function and histology of isolated and perfused hearts from MCT-treated rats. Experiments were performed on 50 male Sprague-Dawley rats [348 ± 6 g (SD)]. Thirty-seven rats received MCT (50 mg/kg sc; MCT group) while the remainder did not (Control group). Three weeks later, pulmonary artery pressure was assessed echocardiographically in 20 MCT and 8 Control rats. The hearts were then excised and perfused in the constant pressure Langendorff mode to determine peak left ventricular pressure (LVP), the peak instantaneous rate of pressure increase (+dP/d tmax) and decrease (−dP/d tmax), as well as the rate pressure product (RPP). Histological sections were subsequently examined. Pulmonary artery pressure was higher in the MCT-treated group compared with the Control group [12.9 ± 6 vs. 51 ± 35.3 mmHg ( P < 0.01)]. Left ventricular systolic function and diastolic relaxation were decreased in the MCT group compared with the Control group (+dP/d tmax4,178 ± 388 vs. 2,801 ± 503 mmHg/s, LVP 115 ± 11 vs. 83 ± 14 mmHg, RPP 33,688 ± 1,910 vs. 23,541 ± 3,858 beats·min−1·mmHg−1, −dP/d tmax−3,036 ± 247 vs. −2,091 ± 389 mmHg/s; P < 0.0001). The impairment of cardiac function was associated with myocarditis and coronary arteriolar medial thickening. Similarly depressed ventricular function and inflammatory infiltration was seen in 12 rats 7 days after MCT administration. Our findings appear unrelated to the degree of PH and indicate a direct cardiotoxic effect of MCT.

scholarly journals The protective effect of thalidomide on left ventricular function in a rat model of diabetic cardiomyopathy

2010 ◽  
Vol 12 (10) ◽  
pp. 1051-1060 ◽  
Author(s):  
Dae-Hee Kim ◽  
Yong-Jin Kim ◽  
Sung-A Chang ◽  
Hye-Won Lee ◽  
Ha-Na Kim ◽  
...  
Keyword(s):  
Left Ventricular Function ◽  
Protective Effect ◽  
Ventricular Function ◽  
Diabetic Cardiomyopathy ◽  
Rat Model ◽  
Left Ventricular

scholarly journals Neuregulin-1 Promotes Myocardial Angiogenesis in Acute Myocardial Infarction Through Regulating PI3K-AKT-eNOS and VEGF/VEGFR2 Signal Pathways

2021 ◽  
Author(s):  
Xiao Ma ◽  
Chengqiang Wu ◽  
Lang Li ◽  
Zhiyu Zeng ◽  
Chun Gui
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Function ◽  
Function Analysis ◽  
Critical Role ◽  
Myocardial Damage ◽  
Capillary Density ◽  
Left Ventricular ◽  
Signal Pathways ◽  
Neuregulin 1

Abstract Background: Myocardial angiogenesis is central to the recovery of acute myocardial infarction (AMI). Neuregulin-1 (NRG-1) plays a critical role in cardiac function, although its role in myocardial angiogenesis is still unclear. The aim of this study was to investigate the effects of NRG-1 in myocardial angiogenesis in a rat model of AMI, and elucidate the underlying mechanisms. Methods: AMI was induced by a single ligation of left anterior descending coronary artery, followed by intravenous injection of recombinant human NRG-1 or normal saline for 8 consecutive days. The cardiac function indices were measured using the catheter MPA cardiac function analysis system. Histo-pathological changes were observed by HE. Microvessel density (MVD) was measured by CD31 and α-SMA immunostaining. The expression levels of other proteins were assessed by Western blotting. Results: NRG-1 improved cardiac function and alleviated myocardial damage induced by AMI. Compared to the sham-operated group, the capillary density and arteriole density increased after AMI (P<0.05), and were augmented by NRG-1 which also significantly increased the left ventricular function (P<0.05). Furthermore, Compared with sham group, PI3K-AKT-eNOS signaling was decreased significantly (P<0.05) whereas VEGF/ VEGFR2 signaling was significantly increased（P<0.05）in AMI group and both of therm were further upregulated by NRG-1 (P > 0.05).Conclusion: NRG-1 improved cardiac function and promoted myocardial angiogenesis post AMI by up-regulating VEGF and activating the PI3K-Akt-eNOS pathway.

Abstract 20445: Pras40 Prevents Development of Diabetic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mirko Volkers ◽  
Shirin Doroudgar ◽  
Christopher Glembotski ◽  
Mark Sussman
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Myocardial Dysfunction ◽  
Serum Glucose ◽  
Left Ventricular ◽  
Control Group ◽  
Diabetic Patients ◽  
Metabolic Function ◽  
Hypertrophic Growth

Introduction: Diabetes is a multi organ disease and diabetic cardiomyopathy can result in heart failure, which is a leading cause of morbidity and mortality in diabetic patients. Defects in mTOR signaling are believed to contribute to metabolic dysfunctions in diabetic liver and hearts, but evidence is missing that mTOR activation is causal to the development of diabetic cardiomyopathy. PRAS40 (Proline Rich Akt Substrate of 40kDa) is a specific component of mTORC1 that interacts with RAPTOR to inhibit mTORC1 kinase activity Methods and Results: The db/db mouse exhibits key characteristics of T2DM, namely hyperinsulinemia, insulin resistance, hyperglycemia, and develops diabetic cardiomyopathy with decreased cardiac function. Selective mTORC1 inhibition in cardiomyocytes from db/db mice in vivo was achieved using PRAS40 delivered via recombinant cardiotropic adeno-associated vector serotype 9 (AAV9) driven by a cardiomyocyte-specific myosin light chain (MLC2v) promoter construct. Myocardial dysfunction was prevented in AAV-PRAS40 treated db/db mice compared to the AAV-Control group, as seen by significantly higher cardiac ejection fraction (EF%), fractional shortening (FS%) measured by serial echocardiography, despite similar increases in body weight, serum glucose levels, and fat deposition in the liver. The effects of PRAS40 were tested in a model of T2DM induced by high fat diet (HFD). AAV-PRAS40 or AAV-Control was injected at 7 weeks of age and mice were fed HFD chow of or standard for an additional 25 weeks. Decreased cardiac function was observed in the HFD control group measured by echocardiography. This preservation of function was associated with decreased left ventricular diastolic dimension (LVID) and improved diastolic function. This phenotype was associated with improved metabolic function, blunted hypertrophic growth, and preserved insulin sensitivity. Conclusions: mTORC1 inhibition with PRAS40 prevents diabetic cardiomyopathy and improves metabolic function in diabetic mice. These findings may open novel avenues for therapeutic strategies using PRAS40 directed against diabetic-related diseases.

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