Abstract-Matrix remodeling plays an important role in the physiological and pathological remodeling of blood vessels.We specifically investigated the role of matrix metalloproteinase (MMP)-9, an MMP induced during arterial remodeling, by assessing the effects of genetic MMP-9 deficiency on major parameters of arterial remodeling using the mouse carotid artery flow cessation model. Compared with remodeling of matched wild-type (WT) arteries, MMP-9 deficiency decreased intimal hyperplasia, reduced the late lumen loss, eliminated the correlation between intimal hyperplasia and geometric remodeling, and led to significant accumulation of interstitial collagen. Biochemical analysis of MMP-9 knockout (KO) arterial tissue and isolated smooth muscle cells (SMCs) confirmed the lack of MMP-9 expression or compensation by other gelatinases. To investigate potential mechanisms for the in vivo observations, we analyzed in vitro effects of MMP-9 deficiency on the migration, proliferation, and collagen gel contracting capacity of aortic SMCs isolated from MMP-9 KO and WT mice. Although proliferation was comparable, we found that MMP-9 -deficient cells had not only decreased migratory activity, but they also had decreased capacity to contract collagen compared with WT cells. Thus, MMP-9 appears to be involved not only in degradation, but also in reorganization of a collagenous matrix, both facets being essential for the outcome of arterial remodeling. Our results also establish MMP-9 as an attractive therapeutic target for limiting the effects of pathological arterial remodeling in restenosis and atherosclerosis. Key Words: matrix degradation Ⅲ cell migration Ⅲ restenosis Ⅲ atherosclerosis P hysiological and pathological vascular remodeling in response to a variety of stimuli, including hemodynamic changes, inflammation, and injury, leads to reshaping of the vessel wall. Inappropriate remodeling is currently thought to be the main cause of most prevalent vascular pathologies of arteries, including atherosclerosis and restenosis. 1 Degradation of the matrix scaffold enables cell movement and general tissue reorganization, making specialized enzymes called matrix metalloproteinases (MMPs) 2 prime candidates for agents of vascular remodeling. 3 Although many studies have addressed and endorsed a role for MMPs in pathological remodeling, suggesting these as potential therapeutic targets in restenosis and atherosclerosis, due to the current lack of specific MMP inhibitors, such studies could not resolve the identity of the specific relevant MMP(s). We thus decided to explore the effects of MMP-9 genetic deficiency on the remodeling of carotid arteries in the flow cessation murine model, 4 which allows investigation of both formation of intimal hyperplasia and arterial geometrical remodeling, 5 the two main processes implicated in the stenotic remodeling of human arteries. Materials and Methods Animal ModelMMP-9 expression was disrupted by deletion of most of the exon 2 of the MMP-9 gene in the 129/SvEv genetic background (Jackson La...

MMP-9 induction is associated with the formation of intimal hyperplasia and does not require frank mechanical injury. Our data also show that a significant increase in MMP-9 expression preceded the positive geometrical remodeling of arteries, suggesting a potentially beneficial role for this matrix-degrading enzyme.

An interferometric biosensor comprised of two layers of porous Si, stacked one on top of the other, is described. A fast Fourier transform (FFT) of the reflectivity spectrum reveals three peaks that correspond to the optical thickness of the top layer, the bottom layer, and both layers together. Binding of immunoglobulin G to a protein A capture probe adsorbed to the surface of the top layer induces changes in reflectivity at the top layer/solution interface. The FFT method allows discrimination of target analyte binding from matrix effects due to nonspecific changes in the analyte solution. The sensor response is shown to be insensitive to the addition of 4000-fold excess sucrose or 80-fold excess bovine serum albumin interferents.