The role of monocyte-derived cells and inflammation in baboon ductus arteriosus remodeling.
Inflammatory processes play a crucial role in the pathogenesis of atherosclerosis and other vascular disorders. We hypothesized that ischemia of the ductus arteriosus might initiate an active inflammatory response that could play a role in ductus remodeling and permanent closure. To test this hypothesis, we studied effects of postnatal ductus construction on inflammatory processes and remodeling in late-gestation fetal and newborn baboons, and preterm newborn baboons. After postnatal ductus constriction, the expression of several genes known to be essential for atherosclerotic remodeling [vascular cell adhesion molecule (VCAM)-1, E-selectin, IL-8, macrophage colony stimulating factor-1, CD154, interferon-gamma, IL-6, and tumor necrosis factor-alpha] was increased in the ductus wall. We were unable to detect intercellular adhesion molecule (ICAM)-1, ICAM-2, P-selectin, monocyte chemoattractant protein-1, or IL-1 by either real-time PCR or immunohistochemistry. VCAM-1, which is newly expressed by luminal cells of the closed ductus, is an important ligand for the mononuclear cell adhesion receptor VLA4. After postnatal constriction, VLA4+ monocytes/macrophages (CD68+ and CD14+) and, to a lesser extent, T-lymphocytes adhered to the ductus wall. Neutrophils and platelets were not observed. The extent of postnatal neointimal remodeling (both endothelial cell layering and subendothelial space thickening) was associated with the degree of mononuclear cell adhesion. Similarly, the extent of vasa vasorum ingrowth correlated with the invasion of CD68+ cells, from the adventitia into the muscle media. Based on these data, we conclude that the inflammatory response following postnatal ductus constriction may be as necessary for ductus remodeling as it is for atherosclerotic remodeling.
Waleh
Nahid
N
Cardiovascular Research Institute, Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143-0544, USA.
Seidner
Steven
S
McCurnin
Donald
D
Yoder
Bradley
B
Liu
Bao Mei
BM
Roman
Christine
C
Mauray
Françoise
F
Clyman
Ronald I
RI
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001161:Arteriosclerosis / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis; D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004373:Ductus Arteriosus / Q000196:embryology* / Q000378:metabolism*; D019040:E-Selectin / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation; D039041:Integrin alpha4beta1 / Q000096:biosynthesis; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D010215:Papio; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D020257:Ventricular Remodeling; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D023201:CD40 Ligand; D018932:Chemokine CCL2; D019040:E-Selectin; D039041:Integrin alpha4beta1; D007375:Interleukin-1; D016209:Interleukin-8; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012313:RNA; D019010:Vascular Cell Adhesion Molecule-1; C067980:CD68 antigen, human; D000097382:CD68 Molecule