Macrophages, myofibroblasts and neointimal hyperplasia after coronary artery injury and repair.
Macrophages participate in the restenosis process through the release of cytokines, metalloproteinases and growth factors. Studies of peritoneal granulation tissue suggest that macrophages may be precursors of myofibroblasts. This study examined the contribution of monocyte/macrophage lineage cells to neointimal cellular mass in a porcine model of thermal vascular injury. Thermal coronary artery injury caused medial smooth muscle cell necrosis and transformation of the media into an extracellular matrix barrier. The neointimal hyperplasia that developed over the injury sites was evaluated by light microscopy, electron microscopy and immunohistochemistry. At day 3, blood monocytes were adhered to the vessel wall and infiltrated the fibrotic media. At day 14, 42+/-3.9% of neointimal cells had a monocytic nuclear morphology and expressed macrophage-specific antigen SWC3 (identified by monoclonal antibody DH59B). Moreover, 9.2+/-1.8% of neointimal cells co-expressed SWC3 and alpha-smooth muscle actin and had ultrastructural characteristics intermediate between macrophages and myofibroblasts. At day 28, 10.5+/-3.5% of cells expressed SWC3 and 5.2+/-1.8% of cells co-expressed SWC3 and alpha-smooth muscle actin. This study indicates that hematopoietic cells of monocyte/macrophage lineage abundantly populate the neointima in the process of lesion formation and may be precursors of neointimal myofibroblasts after thermal vascular injury.
Bayes-Genis
Antoni
A
The Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA. abayesgenis@hsp.santpau.es
Campbell
Julie H
JH
Carlson
P J
PJ
Holmes
David R
DR
Schwartz
Robert S
RS
D000704:Analysis of Variance; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003327:Coronary Disease / Q000473:pathology* / Q000601:surgery*; D003331:Coronary Vessels / Q000293:injuries*; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006097:Granulation Tissue / Q000473:pathology; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000502:physiology*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D015425:Myocardial Reperfusion; D009336:Necrosis; D011336:Probability; D012038:Regeneration / Q000502:physiology*; D013552:Swine; D017539:Tunica Intima / Q000473:pathology