Korshunov Vyacheslav A, Solomatina Marina A, Plekhanova Olga S, Parfyonova Yelena V, Tkachuk Vsevolod A, Berk Bradford C
Center for Cardiovascular Research, Aab Institute of Biomedical Sciences and Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA.
J Vasc Res. 2004 Nov-Dec;41(6):481-90. doi: 10.1159/000081804. Epub 2004 Oct 28.
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.
颈动脉内膜中层增厚（IMT）是血管重塑的一种形式，与人类冠状动脉疾病风险密切相关。响应血流的血管重塑是一个复杂的过程，关键涉及细胞与基质相互作用的改变。为深入了解这些事件，我们对两种近交系小鼠品系进行了部分颈动脉结扎（左颈动脉（LCA）=低流量，右颈动脉（RCA）=高流量）：C57Bl/6J（C57）和FVB/NJ（FVB）。为评估两种主要的基质降解系统，即纤溶酶原激活剂（PAs）和基质金属蛋白酶（MMPs）的作用，我们比较了C57和FVB小鼠结扎颈动脉中u-PA、t-PA、MMP-2和MMP-9的表达。与高流量的RCA相比，低流量的LCA引起的重塑程度更大。尽管两种品系的LCA流量都有类似程度的降低，但结扎后FVB小鼠的最大IMT体积（82±7×10⁻⁶立方毫米）大于C57小鼠（38±4×10⁻⁶立方毫米）。在PAs和MMPs中，t-PA和u-PA表达的增加与IMT的增加相关（分别为p<0.0005和p<0.001）。MMP-2、MMP-9和金属蛋白酶组织抑制剂-2的表达也增加，但品系间无差异。总之，血流诱导的颈动脉IMT由基因决定，并且与两种近交系小鼠品系中的t-PA和u-PA表达相关。
