Remodeling of the adventitia during coronary arteriogenesis.
We studied the role of the adventitia in adaptive arteriogenesis during the phase of active growth of coronary collateral vessels (CV) induced by chronic occlusion of the left circumflex coronary artery in canine hearts. We used electron microscopy and immunoconfocal (IF) labeling for bFGF, matrix metalloproteinase (MMP)-2, MMP-9, tissue-type plasminogen activator (tPA), its inhibitor (PAI-1), fibronectin (FN), and Ki-67. Proliferation of smooth muscle cells and adventitial fibroblasts was evident. Quantitative IF showed that adventitial MMP-2, MMP-9, and FN were 9.2-, 7.5-, and 8.6-fold, bFGF was 5.1-fold, and PAI-1 was 3.4-fold higher in CV than in normal vessels (NV). The number of fibroblasts was 5-fold elevated in CV, but the elastic fiber content was 25-fold greater in NV than in CV. Perivascular myocyte damage and induction of endothelial nitric oxide synthase in peri-CV capillaries indicate expansion of CV. It was concluded that adventitial activation is associated with the development of CV through cell proliferation, production of growth factors, and induction of extracellular proteolysis thereby contributing to remodeling during adaptive arteriogenesis.
Cai
Wei-Jun
WJ
Max Planck Institute, Department of Experimental Cardiology, D-61231 Bad Nauheim, Germany.
Koltai
Sophie
S
Kocsis
Elisabeth
E
Scholz
Dimitri
D
Kostin
Sawa
S
Luo
Xuegang
X
Schaper
Wolfgang
W
Schaper
Jutta
J
D000818:Animals; D001158:Arteries / Q000503:physiopathology; D001808:Blood Vessels / Q000503:physiopathology; D002455:Cell Division; D003097:Collateral Circulation; D003238:Connective Tissue / Q000473:pathology / Q000503:physiopathology*; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D006128:Growth; D019394:Ki-67 Antigen / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D005353:Fibronectins; D019394:Ki-67 Antigen; D017395:Plasminogen Activator Inhibitor 1; D016222:Fibroblast Growth Factor 2; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9