Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late After Myocardial Infarction
| Autor: | Drew DeBay, Audrey W. Li, Chris V. Bowen, Mohammed Althobaiti, Stacy B. O'Blenes, James R. Clarke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Pathology Clinical Biochemistry heart failure Internal medicine medicine Pharmacology (medical) Myocardial infarction General Pharmacology Toxicology and Pharmaceutics cell transplantation Acute mi Original Research Ejection fraction business.industry Skeletal Myoblasts lcsh:RM1-950 Cancer General Medicine medicine.disease Transplantation myocardial infarction lcsh:Therapeutics. Pharmacology Heart failure Cardiology Hepatocyte growth factor business medicine.drug |
| Zdroj: | Drug Target Insights, Vol 2013, Iss 7, Pp 9-17 (2013) Drug Target Insights Drug Target Insights, Vol 7 (2013) |
| ISSN: | 1177-3928 |
| Popis: | In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which correlates with decreased hepatocyte growth factor (HGF) expression, an important regulator of SKMB function. Here, we investigated delivery of exogenous HGF as a strategy for augmenting SKMB engraftment late after MI. Rats underwent SKMB transplantation 4 weeks after coronary ligation. HGF or vehicle control was delivered intravenously during the subsequent 2 weeks. LV function was assessed by MRI before and 2 weeks after SKMB transplantation. We evaluated HGF delivery, SKMB engraftment, and expression of genes associated with post-MI remodeling. Serum HGF was 6.2 ± 2.4 ng/mL after 2 weeks of HGF infusion (n = 7), but undetectable in controls (n = 7). LV end-diastolic volume and ejection fraction did not improve with HGF treatment (321 ± 27 mm 3 , 42% ± 2% vs. 285 ± 33 mm 3 , 43% ± 2%, HGF vs. control). MIs were larger in HGF-treated animals (50 ± 7 vs. 30 ± 6 mm 3 , P = 0.046), but the volume of engrafted SKMBs or percentage of MIs occupied by SKMBs did not increase with HGF (1.7 ± 0.3 mm 3 , 4.7% ± 1.9% vs. 1.4 ± 0.4 mm 3 , 5.3% ± 1.6%, HGF vs. control). Expression of genes associated with post-infarction remodeling was not altered by HGF. Delivery of exogenous HGF failed to augment SKMB engraftment and functional recovery in chronic MI. Expression of genes associated with LV remodeling was not altered by HGF. Alternative strategies to enhance engraftment of SKMB must be explored to optimize the clinical efficacy of SKMB transplantation. |
| Databáze: | OpenAIRE |
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