title: Humoral and cellular factors responsible for coronary collateral formation.
abstract: Clinical observations suggest that patients with coronary artery disease (CAD) display a marked heterogenerty in collateral formation despite similar degrees of coronary obstruction. The development of coronary collaterals helps protect the myocardium from ischemic damage, yet the factors responsible for collateral formation are poorly understood. To better understand the biochemical and cellular mechanisms of collateral artery formation, monocyte function and circulating levels of pro- and antiangiogenic factors were measured in 101 patients with angiographically assessed CAD and extensively developed (score 2, n = 33) or absent (score 0, n = 68) collateral circulations. Compared with patients with score 0, those with score 2 were slightly older and had more advanced CAD. The score 2 group was also more likely to have had a previous myocardial infarction or coronary artery bypass grafting and a family history of CAD. At the same time, there were no significant differences between groups with regard to circulating levels of vascular endothelial growth factor-A(165), platelet-derived growth factor-betabeta, fibroblast growth factor-2, fibroblast growth factor-4, hepatocyte growth factor, tumor necrosis factor-alpha, interleukin-1beta, endostatin, matrix metalloproteinase-9, promatrix metalloproteinase-1, and CD40 ligand. Monocytes isolated from patients with score 2 and 0 collateral circulations demonstrated no differences in migration assays. However, adhesion to fibrinogen and collagen was significantly higher for monocytes from patients with score 0 (p = 0.05 and 0.04, respectively). In conclusion, these data suggest that the degree of coronary collateral formation is not determined by differences in systemically measurable levels of pro- or antiangiogenic factors assessed in this study. Rather, cellular properties, such as cell adhesion, or genetic differences between patients may be the driving force for collateral development.
authors.affiliation: Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Sherman
authors.forename: Amy
authors.initials: A
authors.lastname: Hall
authors.forename: David J
authors.initials: DJ
authors.lastname: Malenka
authors.forename: Ebo D
authors.initials: ED
authors.lastname: De Muinck
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
mesh_terms: D000328:Adult; D000368:Aged; D000077214:Becaplermin; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D002448:Cell Adhesion; D003097:Collateral Circulation; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003326:Coronary Circulation; D043169:Endostatins / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D051519:Fibroblast Growth Factor 4 / Q000097:blood; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D043169:Endostatins; D051519:Fibroblast Growth Factor 4; D053583:Interleukin-1beta; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D023201:CD40 Ligand; D000077214:Becaplermin; D017228:Hepatocyte Growth Factor; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1