Circulating humoral factors and endothelial progenitor cells in patients with differing coronary collateral support
Pier D Lambiase1, Richard J Edwards, Prodromos Anthopoulos
1Department of Cardiology, GKT School of Medicine, The Rayne Institute, St Thomas' Hospital, London, UK.
Insights
Reduced circulating endothelial progenitor cells (EPCs) are linked to poor coronary collateral development in patients with coronary artery disease. Augmenting EPCs may enhance collateral formation.
Area of Science:
- Cardiovascular Research
- Angiogenesis
- Vascular Biology
Background:
- Mechanisms of variable coronary collateral formation in patients with similar coronary artery disease patterns are not fully understood.
- This study explores the role of circulating humoral and cellular factors in this variation.
Purpose of the Study:
- To investigate the association between circulating factors and coronary collateral development.
- To determine if reduced endothelial progenitor cells (EPCs) or altered growth factor activity contribute to inadequate collateralization.
Main Methods:
- Assessed collateral flow index (CFI) in 30 patients with isolated left anterior descending coronary artery disease post-percutaneous coronary intervention.
- Measured coronary sinus growth factors, plasma angiogenic and mitogenic activity, and circulating CD34/CD133-positive hemopoietic precursor cells and differentiated EPCs.
Main Results:
- Patients with inadequate collateralization (CFI <0.25) showed lower growth factor concentrations and weaker plasma proangiogenic effects.
- A strong positive correlation was found between circulating hemopoietic precursor cells and CFI (r=0.75, P<0.001).
- Significantly reduced numbers of differentiated EPCs were observed in patients with inadequate collateralization (75% reduction in circulation, 70% in culture).
Conclusions:
- Inadequate coronary collateral development is associated with reduced circulating EPCs and impaired chemotactic/proangiogenic activity.
- Findings support therapeutic strategies aimed at augmenting circulating EPCs to enhance coronary collateral formation.
Background:
The mechanisms underlying the variation in collateral formation between patients, even with similar patterns of coronary artery disease, remain unclear. This study investigates whether circulating humoral or cellular factors can provide an insight into this variation.
Methods And Results:
Thirty patients with isolated left anterior descending coronary artery disease underwent percutaneous coronary intervention with collateral flow index (CFI) determined using a pressure wire. Patients with inadequate (CFI <0.25) compared with those with adequate (CFI > or =0.25) collateral support had, or tended to have, lower concentrations of coronary sinus growth factors and plasma exerting a weaker effect on endothelial cell migration and angiogenesis in vitro. However, there was an inverse correlation between serum mitogenicity and CFI (r=-0.61, P<0.01). No significant differences were detected between the 2 groups in plasma levels of total vascular endothelial growth factor, vascular endothelial growth factor165, or placental growth factor. There was a strong positive correlation between numbers of CD34/CD133-positive circulating hemopoietic precursor cells and CFI (r=0.75, P<0.001). In patients with inadequate, compared with those with adequate, CFI, the numbers of differentiated endothelial progenitor cells (EPCs) appearing in the circulation and in culture were significantly reduced by 75% (P<0.05) and 70% (P<0.05), respectively.
Conclusions:
In this study, inadequate coronary collateral development is associated with reduced numbers of circulating EPCs and impaired chemotactic and proangiogenic but not mitogenic activity. These findings are consistent with current efforts to enhance collateral formation by augmentation of circulating EPCs.
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