scholarly journals Myocardial transfection with naked DNA plasmid encoding hepatocyte growth factor prevents the progression of heart failure in dogs

2011 ◽  
Vol 300 (4) ◽  
pp. H1501-H1509 ◽  
Author(s):  
Sharad Rastogi ◽  
Mayra Guerrero ◽  
Mengjun Wang ◽  
Itamar Ilsar ◽  
Michael S. Sabbah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Low Dose ◽  
Left Ventricular ◽  
Lv Function ◽  
High Dose ◽  
Naked Dna ◽  
Dna Plasmid ◽  
Hepatocyte Growth

This study examined the effects of localized intramyocardial injections of hepatocyte growth factor (HGF) naked DNA plasmid on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Twenty-one dogs with intracoronary microembolization-induced HF [LV ejection fraction (EF) = 35–40%] were randomized into three treatment groups, namely, high-dose HGF plasmid (4.0 mg, n = 7), low-dose HGF plasmid (0.4 mg, n = 7), and sham-operated controls treated with normal saline ( n = 7). A total of 10–15 injections of HGF plasmid or saline were made directly into the anterior wall of LV. LV EF and end-systolic volume (ESV) were measured before randomization (pretreatment) and at the end of 3 mo of follow-up (posttreatment). Treatment effect (Δ) was calculated as the change from pre- to posttreatment. Protein expression of sarcoplasmic reticulum (SR) Ca2+-cycling proteins was determined in LV tissue obtained from the sites of HGF injection and remote areas. Low-dose HGF attenuated the decline in EF (ΔEF: −3 ± 1 vs. −8 ± 1%, P < 0.05) and the increase in ESV (ΔESV: 6 ± 2 vs. 10 ± 1 ml, P < 0.05) seen in control sham-operated dogs, whereas high-dose HGF significantly increased EF (ΔEF: 4 ± 1 vs. −8 ± 1%, P < 0.05) and prevented the increase in ΔESV (ESV: −1 ± 1 vs. 10 ± 1 ml, P < 0.05) compared with control dogs. Treatment with high- and low-dose HGF improved the expression of the SR Ca2+-cycling proteins compared with controls. In conclusion, regional intramyocardial injections of HGF naked DNA plasmid improve regional and global LV function and prevent progressive LV remodeling.

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.

Abstract 621: High-dose gefitinib overcomes the resistance to gefitinib related to hepatocyte growth factor

2010 ◽  
Author(s):  
Hiromi Kashihara ◽  
Eiki Ichihara ◽  
Saburo Takata ◽  
Kadoaki Ohashi ◽  
Toshio Kubo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
High Dose ◽  
Hepatocyte Growth

Pretreatment hepatocyte growth factor and thrombospondin-1 levels predict response to high-dose chemotherapy for multiple myeloma

Neoplasma ◽  
2010 ◽  
Vol 57 (1) ◽  
pp. 29-34 ◽  
Author(s):  
L. POUR ◽  
H. SVACHOVA ◽  
Z. ADAM ◽  
Z. MIKULKOVA ◽  
L. BURESOVA ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Thrombospondin 1 ◽  
Hepatocyte Growth

Evidence for association of coronary sinus levels of hepatocyte growth factor and collateralization in human coronary disease

2003 ◽  
Vol 284 (5) ◽  
pp. H1507-H1512 ◽  
Author(s):  
Daniel J. Lenihan ◽  
Abdulfatah Osman ◽  
Vissa Sriram ◽  
Julius Aitsebaomo ◽  
Cam Patterson
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Coronary Sinus ◽  
Left Ventricular ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Artery Disease ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth ◽  
Collateral Formation

The therapeutic use of angiogenic factors to protect ischemic myocardium is limited by our incomplete understanding of their endogenous production. We determined the association between angiogenic factors and collateral formation in patients with coronary artery disease (CAD). A total of 71 patients underwent catheterization with sampling of the pulmonary artery, aorta, and coronary sinus (CS) to determine the levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). VEGF and HGF levels were not different in the three vascular sites, suggesting that the heart is not a major source of these cytokines in the circulation. CS VEGF and HGF levels were similar in patients with and without CAD. Elevated CS HGF levels were associated with collateral formation, whereas VEGF levels were not. Additionally, CS HGF was significantly elevated in patients with left ventricular dysfunction. These data map for the first time the concentration of endogenous angiogenic factors in the coronary circulation and support further studies to determine whether HGF may be an endogenous cardioprotective angiogenic factor.

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