Abnormal angiogenesis and
vascular remodeling contribute to pathogenesis of a number of disorders such as
tumor,
arthritis,
atherosclerosis, restenosis,
hypertension, and neurodegeneration. During angiogenesis and
vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) and its interaction with extracellular matrix (ECM) play a critical role in the processes.
Matrix metalloproteinases (
MMPs), well-known inflammatory mediators are a family of
zinc-dependent
proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and
pathological processes.
MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and
MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated,
MMPs degrade ECM
proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by
MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and
vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of
MMPs shows therapeutic potential.