Plasminogen activator expression correlates with genetic differences in vascular remodeling.

Abstract:

: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.

journal_name

J Vasc Res

authors

Korshunov VA,Solomatina MA,Plekhanova OS,Parfyonova YV,Tkachuk VA,Berk BC

doi

10.1159/000081804

keywords:

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

481-90

issue

6

eissn

1018-1172

issn

1423-0135

pii

81804

journal_volume

41

pub_type

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