Abstract
Matrix Metalloproteinases (MMPs) are a family of glycoprotein enzymes, which are zinc-dependent endoproteinases. These degradative enzymes digest the blood-vessel walls to allow endothelial cells to escape and migrate toward the site of the angiogenic stimuli. MMPs play a role in angiogenesis in many different ways; endothelial cell migration caused by surrounding tissues by interrupting ECM barriers, release of angiogenic factors, such as fibroblast growth factor-2 or vascular endothelial growth factor. MMP-2, also known as Gelatinase-A, is type IV collagenase which can not only break down type IV collagen of the basal laminae but also other areas of non-helical collagen and proteins such as Fibronectin, Laminin, Natural Insoluble Elastin, Aggregan, and Vitronectin. Many different cell types express MMP-2, such as fibroblasts, keratinocytes, endothelial cells, chondrocytes and monocytes. MMP-2 is known to contribute in various diseases, such as atherosclerosis and skeletal disorder. MMP2 can regulate pathological growth in vasculature and plays a role in angiogenesis of variety of diseases by releasing angiogenic factors and assisting in cell migration and cell adhesion. Further, MMP-2 can be a potential cause in initial tumor formation by altering ECM, which provides optimal environment for tumor growth. Hence, understanding the pathological and physiological aspects of MMP-2 remains crucial in order to develop therapeutic interventions.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Bellafiore M, Battaglia G, Bianco A, Farina F, Palma A, Paoli A (2013) The involvement of MMP-2 and MMP-9 in heart exercise-related angiogenesis. J Transl Med 11(1):283. doi:10.1186/1479-5876-11-283
Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9(6):653–660. doi:10.1038/nm0603-653 nm0603-653 [pii]
Clements KM, Price JS, Chambers MG, Visco DM, Poole AR, Mason RM (2003) Gene deletion of either interleukin-1?, interleukin-1?-converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomy. Arthritis Rheum 48(12):3452–3463. doi:10.1002/art.11355
Corry DB (2004) Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J 18:995–997. doi:10.1096/fj.03-1412fje
Fanjul-Fernández M, Folgueras AR, Cabrera S, López-Otín C (2010) Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models. Biochim Biophys Acta Mol Cell Res 1803(1):3–19. doi:10.1016/j.bbamcr.2009.07.004
Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6(4):273–286. doi:10.1038/nrd2115
Gormus U, Kahraman OT, Isbir S, Tekeli A, Isbir T (2011) MMP2 gene polymorphisms and MMP2 mRNA levels in patients with superficial varices of lower extremities. In Vivo (Athens, Greece) 25(3):387–391
Inoue K, Mikuni-Takagaki Y, Oikawa K, Itoh T, Inada M, Noguchi T, Park JS, Onodera T, Krane SM, Noda M, Itohara S (2006) A crucial role for matrix metalloproteinase 2 in osteocytic canalicular formation and bone metabolism. J Biol Chem 281(44):33814–33824. doi:10.1074/jbc.m607290200
Kurz H, Burri PH, Djonov VG (2003) Angiogenesis and vascular remodeling by intussusception: from form to function. Physiology 18(2):65–70. doi:10.1152/nips.01417.2002
Kuzuya M (2006) Effect of MMP-2 deficiency on atherosclerotic lesion formation in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 26(5):1120–1125. doi:10.1161/01.atv.0000218496.60097.e0
Murillo CA, Woodside KJ, Guo Q, Zhang S, O’Connor KL, Hunter GC (2009) Integrin and matrix metalloproteinase expression in human carotid plaque. J Surg Res 155(1):157–164. doi:10.1016/j.jss.2008.08.005
Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8(3):221–233. doi:10.1038/nrm2125
Raffetto JD, Ross RL, Khalil RA (2007) Matrix metalloproteinase 2–induced venous dilation via hyperpolarization and activation of K+ channels: relevance to varicose vein formation. J Vasc Surg 45(2):373–380. doi:10.1016/j.jvs.2006.10.041
Rundhaug JE (2005) Matrix metalloproteinases and angiogenesis. J Cell Mol Med 9(2):267–285. doi:10.1111/j.1582-4934.2005.tb00355.x
Shah PK, Galis ZS (2001) Matrix metalloproteinase hypothesis of plaque rupture: players keep piling up but questions remain. Circulation 104(16):1878–1880
Tutton MG, George ML, Eccles SA, Burton S, Swift RI, Abulafi AM (2003) Use of plasma MMP-2 and MMP-9 levels as a surrogate for tumour expression in colorectal cancer patients. Int J Cancer 107(4):541–550. doi:10.1002/ijc.11436
Vu TH (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14(17):2123–2133. doi:10.1101/gad.815400
Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ, Chapman HA, Shapiro SD, Elias JA (2000) Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase– and cathepsin-dependent emphysema. J Clin Investig 106(9):1081–1093. doi:10.1172/jci10458
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Salajegheh, A. (2016). Matrix Metalloproteinase 2 (MMP2). In: Angiogenesis in Health, Disease and Malignancy. Springer, Cham. https://doi.org/10.1007/978-3-319-28140-7_31
Download citation
DOI: https://doi.org/10.1007/978-3-319-28140-7_31
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-28138-4
Online ISBN: 978-3-319-28140-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)