Plasminogen activator expression correlates with genetic differences in vascular remodeling.
Intima-media thickening (IMT) of the carotid artery, a form of vascular remodeling, correlates well with coronary artery disease risk in humans. Vascular remodeling in response to blood flow is a complex process that critically involves altered cell matrix interactions. To gain insight into these events, we performed partial carotid ligation (left carotid (LCA) = low flow and right carotid (RCA) = high flow) in 2 inbred mouse strains: C57Bl/6J (C57) and FVB/NJ (FVB). To evaluate the role of the 2 major matrix-degrading systems, plasminogen activators (PAs) and matrix metalloproteinases (MMPs), we compared the expression of u-PA, t-PA, MMP-2 and MMP-9 in ligated carotids of C57 and FVB mice. The extent of remodeling was greater in response to low LCA than high RCA flow. Despite a similar decrease in LCA flow in both strains, maximal IMT volume was greater in FVB (82 +/- 7 x 10(-6) microm(3)) than in C57 (38 +/- 4 x 10(-6) microm(3)) after ligation. Among PAs and MMPs, increased expression of t-PA and u-PA correlated with increased IMT (p < 0.0005 and p < 0.001, respectively). MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-2 expression also increased, but did not differ between strains. In summary, flow-induced IMT of the carotid is genetically determined and correlates with t-PA and u-PA expression in 2 inbred mouse strains.
Korshunov
Vyacheslav A
VA
Center for Cardiovascular Research, Aab Institute of Biomedical Sciences and Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA.
Solomatina
Marina A
MA
Plekhanova
Olga S
OS
Parfyonova
Yelena V
YV
Tkachuk
Vsevolod A
VA
Berk
Bradford C
BC
D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012039:Regional Blood Flow; D013045:Species Specificity; D013314:Stress, Mechanical; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D019716:Tissue Inhibitor of Metalloproteinase-2; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9