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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Histologic evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser
N Yamamoto1, T Kohmoto, W Roethy
1Department of Cardiovascular Surgery, Okayama University, Okayama City, Japan. nori_y@med.okayama-u.ac.jp
Objectives:
To determine whether addition of basic fibroblast growth factor (bFGF), an angiogenic growth factor, enhances the angiogenic effects of transmyocardial laser revascularization (TMR).
Background:
TMR is an investigational therapy for treating patients with medically refractory angina not amenable to traditional therapies. Histologic and blood flow studies in animals have suggested that TMR enhances angiogenesis above that normally seen in ischemic myocardium. We tested the hypothesis that bFGF administered into TMR channels further enhance the angiogenic effects of TMR.
Methods:
Chronic ischemia was created in 3 groups of dogs using an ameroid constrictor on the proximal LAD. In the bFGF group (n = 5) non-transmyocardial channels were created in the LAD territory and bFGF, (100 ng/ml) dissolved in pluronic gel was injected into the each channel. In the TMR group (n = 7), transmyocardial channels were created without bFGF. A control group (n = 7) had ischemia without TMR of bFGF. 5-bromo-2'-deoxyuridine (BrdU) was administered to mark proliferating cells. After 8 weeks survival, colored microspheres were injected to assess the regional myocardial blood flow.
Results:
TMR and TMR+bFGF increased total vascular density by approximately 40% over that observed in the control group. However, the number of large vessels (internal diameter > or = 50 microm) was doubled by the addition of bFGF, and this correlated with a 50% increase in the density of proliferating vascular cells and a tripling of the total estimated vascular cross sectional area. Blood flow to the LAD territory was increased by TMR compared to controls, with no further benefit observed in the bFGF group.
Conclusions:
On a histologic basis, basic fibroblast growth factor further enhances angiogenesis following TMR in ischemic myocardium mainly by increasing the size but not the total number of vessels.
