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Chapter 6: MOLECULAR AND CELLULAR BIOLOGY OF BLOOD VESSELS THE EXTRACELLULAR MATRIX

The extracellular matrix is a major component of the vessel wall. It is the medium through which nutrients are transported, a repository for products secreted by the cells of the vascular wall, the site of accumulation of cell debris, and a substrate for migration and proliferation of endothelial cells, monocytes, and vascular smooth muscle cells. The matrix consists of several proteins that have distinct functions in maintaining the integrity of the wall (Table 6-1).

Table 6-1: Components of the Extracellular Matrix

Matrix Component

Function

Proteoglycans

Resistance to deformation

Arterial permeability, filtration, ion exchange

Transport and deposition of plasma elements

Regulation of cellular metabolism

Collagens (types I and III) Mechanical strength

Collagens (types IV, V, and VI) Attachment of vascular cells to the matrix

Components of the basal lamina

Linking collagens to noncollagenous structures

Elastin

Regulation of vascular elasticity

Fibronectin

Cell-cell adhesion

Cell-substrate adhesion

Cell motility

Specific binding of collagen, heparin

Laminin

Attachment of endothelial cells to type IV collagen

Extracellular matrix degradation and reformation is an extremely important biological process with profound clinical implications. It is impossible for vascular cells to hypertrophy, proliferate, or migrate without an initial degradation of the matrix. One of the earliest events in angiogenesis is the degradation of the extracellular matrix to enable tube (capillary) formation. Vascular cells, including endothelial cells, VSMCs, resident macrophages and fibroblasts, may secrete matrix metalloproteinases (MMPs), enzymes that selectively digest the individual components of the matrix. In addition, these cells elaborate tissue inhibitors of metalloproteinases (TIMPs).8

MMPs belong to three main groups: the type IV collagenases (also called gelatinases), the stromelysins, and interstitial collagenase. The characteristics of these proteins are described in Table 6-2. MMPs are produced as inactive zymogens that can be activated by plasmin.9 The activity of MMPs is also regulated by cytokines at transcriptional and posttranslational levels, as well as by the relative levels of TIMPs. MMP-

2 is usually found complexed with its specific inhibitor, TIMP-2.

Table 6-2: Matrix Metalloproteinases and Inhibitors

Class

Nomenclature

Molecular Weighta

Vascular Cell Type

Expression

Interstitial collagenase

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