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Basic FGF enhances endothelium-dependent relaxation of the collateral-perfused coronary microcirculation
F W Sellke1, S Y Wang, M Friedman
1Department of Surgery, Beth Israel Hospital, Boston 02215.
The American Journal of Physiology
|October 1, 1994
Summary
Basic fibroblast growth factor (FGF) treatment preserved endothelial function in coronary microvessels experiencing reduced blood flow. This treatment also increased arteriolar density, suggesting FGF aids both endothelial health and blood vessel growth.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Vascular Biology
Background:
- Endothelial dysfunction is a hallmark of coronary artery disease, particularly in areas with compromised blood flow.
- Basic fibroblast growth factor (FGF) is known for its angiogenic properties and potential role in vascular repair.
Purpose of the Study:
- To investigate the effect of sustained periadventitial basic fibroblast growth factor (FGF) delivery on endothelial function in collateral-dependent and normally perfused coronary microcirculation.
- To assess if bFGF can mitigate endothelial dysfunction and promote microvascular adaptation in a porcine model of chronic coronary occlusion.
Main Methods:
- Chronic periadventitial administration of basic fibroblast growth factor (FGF) using microcapsules in a porcine model with ameroid constrictors on the left circumflex coronary artery (LCX).
- Assessment of coronary microvessels (80-170 microns) via video microscopy under pressurized no-flow conditions after 5-8 weeks.
- Evaluation of receptor-mediated and non-receptor-mediated endothelium-dependent and endothelium-independent responses to various vasoactive agents (ADP, serotonin, acetylcholine, A-23187, nitroprusside, KCl).
Main Results:
- Collateral-dependent LCX microvessels in control hearts showed reduced relaxation to ADP and serotonin, and enhanced contraction to acetylcholine.
- Basic fibroblast growth factor (FGF) treatment normalized these receptor-mediated endothelial responses in the LCX region.
- Arteriolar density was significantly increased (4-fold) in the collateral-perfused LCX region of bFGF-treated hearts compared to controls.
- No significant effects of bFGF were observed in the normally perfused left anterior descending (LAD) coronary artery region or on non-receptor-mediated responses.
Conclusions:
- Sustained periadventitial delivery of basic fibroblast growth factor (FGF) preserves receptor-mediated endothelial function in collateral-dependent coronary microcirculation.
- The angiogenic effect of bFGF is linked to its ability to preserve endothelial function in compromised vascular beds.
- Basic fibroblast growth factor (FGF) shows therapeutic potential for managing endothelial dysfunction in ischemic heart disease.