scholarly journals Intramuscular VEGF repairs the failing heart: role of host-derived growth factors and mobilization of progenitor cells

2009 ◽  
Vol 297 (5) ◽  
pp. R1503-R1515 ◽  
Author(s):  
David Zisa ◽  
Arsalan Shabbir ◽  
Michalis Mastri ◽  
Gen Suzuki ◽  
Techung Lee
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Fold Increase ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Therapeutic Effects ◽  
Ventricular Ejection Fraction ◽  
Factor Production ◽  
Growth Factor Production

Skeletal muscle produces a myriad of mitogenic factors possessing cardiovascular regulatory effects that can be explored for cardiac repair. Given the reported findings that VEGF may modulate muscle regeneration, we investigated the therapeutic effects of chronic injections of low doses of human recombinant VEGF-A165 (0.1–1 μg/kg) into the dystrophic hamstring muscle in a hereditary hamster model of heart failure and muscular dystrophy. In vitro, VEGF stimulated proliferation, migration, and growth factor production of cultured C2C12 skeletal myocytes. VEGF also induced production of HGF, IGF2, and VEGF by skeletal muscle. Analysis of skeletal muscle revealed an increase in myocyte nuclear [531 ± 12 VEGF 1 μg/kg vs. 364 ± 19 for saline (number/mm2) saline] and capillary [591 ± 80 VEGF 1 μg/kg vs. 342 ± 21 for saline (number/mm2)] densities. Skeletal muscle analysis revealed an increase in Ki67+ nuclei in the VEGF 1 μg/kg group compared with saline. In addition, VEGF mobilized c-kit+, CD31+, and CXCR4+ progenitor cells. Mobilization of progenitor cells was consistent with higher SDF-1 concentrations found in hamstring, plasma, and heart in the VEGF group. Echocardiogram analysis demonstrated improvement in left ventricular ejection fraction (0.60 ± 0.02 VEGF 1 μg/kg vs. 0.45 ± 0.01 mm for saline) and an attenuation in ventricular dilation [5.59 ± 0.12 VEGF 1 μg/kg vs. 6.03 ± 0.09 for saline (mm)] 5 wk after initiating therapy. Hearts exhibited higher cardiomyocyte nuclear [845 ± 22 VEGF 1 μg/kg vs. 519 ± 40 for saline (number/mm2)] and capillary [2,159 ± 119 VEGF 1 μg/kg vs. 1,590 ± 66 for saline (number/mm2)] densities. Myocardial analysis revealed ∼2.5 fold increase in Ki67+ cells and ∼2.8-fold increase in c-kit+ cells in the VEGF group, which provides evidence for cardiomyocyte regeneration and progenitor cell expansion. This study provides novel evidence of a salutary effect of VEGF in the cardiomyopathic hamster via induction of myogenic growth factor production by skeletal muscle and mobilization of progenitor cells, which resulted in attenuation of cardiomyopathy and repair of the heart.

scholarly journals Transplantation of Endothelial Progenitor Cells in the Treatment of Coronary Artery Microembolism in Rats

2020 ◽  
Vol 29 ◽  
pp. 096368972091268
Author(s):  
Yajun Xue ◽  
Boda Zhou ◽  
Jian Wu ◽  
Guobin Miao ◽  
Kun Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Low Dose ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Endothelial Progenitor ◽  
Ventricular Ejection Fraction

As the impairment of myocardial microenvironments due to coronary microembolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME. Low- (2 × 105) and high- (2 × 106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood-clots into the left ventricle. Echocardiograph was examined before and 1, 7, and 28 days after EPC transplantation; serum cardiac troponin I (cTNI), von Willebrand factor (vWF), and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and vascular endothelial growth factor (VEGF), vWF, and basic fibroblast growth factor (bFGF) expression were examined one day after EPC transplantation. After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by left ventricular ejection fraction significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a proangiogenic, antifibroblast, antifibrosis, and antinecrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

Cardiology ◽  
2016 ◽  
Vol 135 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Shao-Ling Yang ◽  
Ke-Qiang Tang ◽  
Jun-Jia Tao ◽  
Ai-Hong Wan ◽  
Yan-Duan Lin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Function ◽  
Rabbit Model ◽  
Physiological Saline ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Therapeutic Effects ◽  
Ventricular Ejection Fraction ◽  
Cluster Of Differentiation

Objectives: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). Methods: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. Results: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. Conclusion: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

Abstract 1111: Embryoinc Stem Cell Derived Cardiovascular Progenitor Cells Improve Function More Than Hemangioblasts in a Mouse Model of Myocardial Infarction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Eric Adler ◽  
Vincient Chen ◽  
Anne Bystrup ◽  
Wilson Young ◽  
Steve Giovannone ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Mouse Model ◽  
Progenitor Cells ◽  
Myocardial Function ◽  
Es Cells ◽  
Fluorescent Microscopy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

BACKGROUND: Intramyocardial transplantation of stem cells improves left ventricular ejection fraction (EF) in animal studies and preliminary clinical trials. The mechanism may involve either replacement of myocytes or improved vascular supply to existing myocytes. We recently identified an Embyronic Stem cell derived cardiovascular progenitor cell (ES-CPC) that is the common precursor of cardiomyocyte and vascular cell lineages. To determine whether myocyte transplantation improves myocardial function more than angiogenesis alone does, we compared the effect of ES-CPCs to hemangioblasts (vascular/hematopoetic progenitor cells) on EF in a mouse model of myocardial infarction. METHODS: ES-CPC and hemangioblasts were isolated from a doxycycline-responsive, Notch-inducible ES cell line containing Notch 4 cDNA under the control of a tetracycline-inducible promoter. Notch induction of mesoderm-derived ES cells resulted in a CPC phenotype, whereas non-induced cells developed into hemangioblasts. Mice underwent transplantation of 500,000 ES-CPC (n=20), hemangioblasts (n=16), or an equal volume of serum-free media (n=12) 30 minutes after surgically-induced myocardial infarction. All cell lines constitutively expressed green fluorescent protein (GFP). EF was assessed two weeks post-transplantation using 9.4 Tesla MRI. Mice were then euthanized and frozen heart sections were examined using fluorescent microscopy. RESULTS: The mean EF was 59Â ± 15, 46Â ± 17, and 39Â ± 13% in the ES-CPC, hemangioblast, and control groups, respectively (p<0.05 for the differences among all 3 groups; ANOVA). GFP + cells were detected in frozen sections of both the ES-CPC and hemangioblast groups. GFP + cells in ES-CPC treated hearts expressed markers associated with both cardiomyocyte and vascular phenotypes, whereas the GFP + cells in the hemangioblast group expressed markers associated with vascular phenotypes. CONCLUSIONS: Both hemangioblast and ES-CPC transplantation improves EF in a mouse model of myocardial infarction, but ES-CPC transplantation was more effective. This suggests that enhancement of myocardial function by transplantation of both cardiomyocyte and vascular phenotypes exceeds that with vascular phenotypes alone.

scholarly journals Decomposing the Mechanism of Qishen Granules in the Treatment of Heart Failure by a Quantitative Pathway Analysis Method

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1829 ◽  
Author(s):  
Weiquan Ren ◽  
Sheng Gao ◽  
Huimin Zhang ◽  
Yinglu Ren ◽  
Xue Yu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Pathway Analysis ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Therapeutic Effects ◽  
Analysis Tool ◽  
Ventricular Ejection Fraction ◽  
Pathway Analysis Tool

Qishen granules (QSG) have beneficial therapeutic effects for heart failure, but the effects of decomposed recipes, including Wenyang Yiqi Huoxue (WYH) and Qingre Jiedu (QJ), are not clear. In this study, the efficacy of WYH and QJ on heart failure is evaluated by using transverse aortic constriction (TAC) induced mice and the significantly changed genes in heart tissues were screened with a DNA array. Furthermore, a new quantitative pathway analysis tool is developed to evaluate the differences of pathways in different groups and to identify the pharmacological contributions of the decomposed recipes. Finally, the related genes in the significantly changed pathways are verified by a real-time polymerase chain reaction and a Western blot. Our data show that both QJ and WYH improve the left ventricular ejection fraction, which explain their contributions to protect against heart failure. In the energy metabolism, QJ achieves the therapeutic effects of QSG through nicotinamide nucleotide transhydrogenase (Nnt)-mediated mechanisms. In ventricular remodeling and inflammation reactions, QJ and WYH undertake the therapeutic effects through 5′-nucleotidase ecto (Nt5e)-mediated mechanisms. Together, QJ and WYH constitute the therapeutic effects of QSG and play important roles in myocardial energy metabolism and inflammation, which can exert therapeutic effects for heart failure.

scholarly journals Association of serum intact fibroblast growth factor 23 with left ventricular mass and different echocardiographic findings in patients on hemodialysis

2016 ◽  
Vol 4 (3) ◽  
pp. 135-141 ◽  
Author(s):  
Amir Ahmad Nassiri ◽  
Monir Sadat Hakemi ◽  
Reza Safar-Pour ◽  
Ali Ahmadi ◽  
Maryam Tohidi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Left Ventricular Mass ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Fibroblast Growth ◽  
Ventricular Ejection Fraction ◽  
Ventricular Mass ◽  
Lv Mass

Abstract Objectives To determine the association of fibroblast growth factor 23 (FGF23) with left ventricular hypertrophy (LVH) through the assessment of left ventricular (LV) mass and left ventricular mass index (LVMI) in patients on hemodialysis, this study was done. Methods All patients on hemodialysis who are older than 18 years and in whom hemodialysis vintage was at least 6 months were enrolled. All patients were on hemodialysis thrice a week for 4 h using low-flux dialysis filters, polysulfone membranes, reverse osmosis purified water, and bicarbonate-base hemodialysis solution. The exclusion criteria were any respiratory illness or pulmonary infection, cigarette smoking, and the presence of pericarditis or pericardial effusion. Additionally, patients with a known coronary artery disease, any form of cardiac arrhythmias, any cardiomyopathy or severe valvular heart disease diagnosed by echocardiography, acute congestive heart failure (CHF), and acute myocardial infarction were not included. Echocardiography was conducted by an experienced operator for all the enrolled patients using the ACUSON SC2000™ ultrasound system transducer (Siemens), with a frequency bandwidth of: 1.5–3.5 MHz. Patients were considered to have LVH if the LVMI was greater than 134 g/m2 for men and greater than 110 g/m2 for women. Results A total of 61 patients (19 female and 42 male) were enrolled to the study. Mean (± SD) age of the patients was 59.6 ± 13.1 years. The median duration of hemodialysis was 23 (range: 6–120) months. The median predialysis level of FGF23 was 1,977 pg/mL (range: 155–8,870). LVH was seen in 73.8% of the patients (n = 45) and of them 66.7% were male. There was a statistically significant direct correlation between FGF23 and left ventricle diameter in end systole (LVDs) (r = 0.29, P = 0.027). However, the association of FGF23 with LV mass, LVMI, and left ventricular ejection fraction (LVEF) was not significant. Conclusion This study does not show the correlation between FGF23 and LV mass in stable hemodialysis patients.

P5436Angiotensin receptor-neprilysin inhibitor preserved cardiac function via improving angiogenetic ability in mice model of atherosclerosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y S Suematsu ◽  
A I Ideishi ◽  
K T Tashiro ◽  
T K Kuwano ◽  
S M Miura
Keyword(s):  
Heart Failure ◽  
Growth Factor ◽  
Natriuretic Peptide ◽  
Transforming Growth Factor ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Mice Model ◽  
Ventricular Ejection Fraction ◽  
Neprilysin Inhibitor ◽  
Apolipoprotein E Knockout Mice

Abstract Introduction Angiotensin receptor-neprilysin inhibitor (ARNI) increases natriuretic peptide and improves heart failure. We previously reported that ARNI has the effects of suppression of myocardial hypertrophy and fibrosis in addition to reduction of afterload by natriuretic effect. We investigated the effects of ARNI against mice model of atherosclerosis and heart failure. Method and results Apolipoprotein E knockout mice fed high cholesterol diet for 4 weeks were divided into four groups: no treatment (CTL), valsartan 30 mg/kg (VAL), sacubitril (neprilysin inhibitor) 30 mg/kg (SAC), and ARNI 60mg/kg for additional 13 weeks. Body weight and systolic blood pressure in the VAL, SAC and ARNI groups did not show significant differences compared to those in the CTL group. Serum brain natriuretic peptide (BNP) in ARNI group (605±221 pg/ml) was significantly increased than that in VAL (391±57 pg/ml) and SAC (357±91 pg/ml) groups, but not CTL group (393±192 pg/ml). Although the rate of atherosclerotic area in aorta was 16.3±5.8% after treatment, there were no significant differences between the groups. In the CTL group, left ventricular ejection fraction (LVEF, 81.6±4.8%) and fractional shortening (FS, 44.8±5.8%) at baseline were significantly reduced after treatment (67.8±8.2% and 33.3±6.1%). Interestingly, LVEF (76.6±6.7%) and FS (40.1±6.1%) after treatment in the ARNI group were significantly preserved compared to those in the CTL group. In real time polymerase chain reaction analysis of LV after treatment, relative mRNA expression of BNP and angiogenetic factors including ATPase sarcoplasmic/endoplasmic reticulum Ca transporting 2, vascular endothelial growth factor A, cluster of differentiation 34 in ARNI group were significantly increased than those in the CTL group. Transforming growth factor-β in ARNI group was significantly reduced than that in the CTL group. Conclusion Although ARNI did not suppress atherosclerosis in mice, it preserved LVEF via improving angiogenetic ability.

scholarly journals A Meta-Analysis of the Therapeutic Effects of Glucagon-Like Peptide-1 Agonist in Heart Failure

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammed Munaf ◽  
Pierpaolo Pellicori ◽  
Victoria Allgar ◽  
Kenneth Wong
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Animal Studies ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Therapeutic Effects ◽  
Significant Heterogeneity ◽  
Ventricular Ejection Fraction

We conducted a meta-analysis of the existing literature of the therapeutic effects of using GLP-1 agonists to improve the metabolism of the failing heart. Animal studies showed significant improvement in markers of cardiac function, such as left ventricular ejection fraction (LVEF), with regular GLP-1 agonist infusions. In clinical trials, the potential effects of GLP-1 agonists in improving cardiac function were modest: LVEF improved by 4.4% compared to placebo (95% C.I 1.36–7.44, ). However, BNP levels were not significantly altered by GLP-1 agonists in heart failure. In two trials, a modest increase in heart rate by up to 7 beats per minute was noted, but meta-analysis demonstrated this was not significant statistically. The small number of studies plus variation in the concentration and length of the regime between the trials would limit our conclusions, even though statistically, heterogeneity chi-squared tests did not reveal any significant heterogeneity in the endpoints tested. Moreover, studies in non-diabetics with heart failure yielded conflicting results. In conclusion, the use of GLP-1 agonists has at best a modest effect on ejection fraction improvement in heart failure, but there was no significant improvement in BNP levels in the meta-analysis.

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