Disease relevance of MMP-2

• These results implicate PI3K-dependent regulation of MT1-MMP protein synthesis and subsequent activation of latent MMP-2 as critical events in neointimal hyperplasia after vascular injury [1].
• The peroxynitrite-mediated activation of matrix metalloproteinase-2 (MMP-2) and subsequent cleavage of troponin I (TnI) in ventricular myocytes is a detrimental effect of ischemia/reperfusion injury [2].
• A key to limiting venous stenosis formation may lie in inhibiting MMP-2 by adventitial and medial targeting [3].
• We examined the effect of heat-inactivated Streptococcus pneumoniae R6 on MMP-2 and MMP-9 release by cultured aortic and brain capillary endothelial cells [4].
• Among nine MMP isozymes tested, compound 1j displays selective inhibition of MMP-2, -9, and -12 with IC(50) values between 0.20 and 1.51 microuM, and in male golden Syrian hamsters, it shows protection against PPE-induced emphysema [5].

High impact information on MMP-2

• Cruciate ligament metabolism was determined by measuring the following markers of collagen turnover: matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinases 2, C-terminal type I procollagen propeptide (PICP), and the immature collagen-derived crosslink dihydroxylysinonorleucine (DHLNL) [6].
• We observed elevated levels of pro and active MMP-2, PICP, and DHLNL in the cruciate ligaments of DH animals at most ages, compared with BS2 guinea pigs [6].
• Smooth muscle cell outgrowth from the media was regulated by endogenous TIMPs, since TIMP inhibition (recombinant MMP-2 or neutralizing anti-TIMP antibodies) facilitated cell outgrowth (P<0.001) [7].
• These observations were paralleled by the predominant expression of TIMP-1 and -2 in the media (14-fold and 37-fold higher than in adventitia, respectively, P<0.001), whereas higher gelatinolytic activities (MMP-2 and -9) were released from adventitial explants [7].
• MMP-2 activity peaks at day seven in the adventitia and days 19 to 26 in the intima [3].

Chemical compound and disease context of MMP-2

• We developed a chronic porcine model of septic shock and ARDS and hypothesized that blocking the proteases neutrophil elastase (NE) and matrix metalloproteinases (MMP-2 and MMP-9) with the modified tetracycline, COL-3, would significantly improve morbidity in this model [8].

Biological context of MMP-2

• Studies were conducted to define the signal transduction pathway responsible for the increases in MMP-2 and -14 that occur in response to mechanical stretching of TM cells [9].
• Translational initiation involving eIF-4E and its inhibitory binding protein 4E-BP1 appear to be involved in both the MMP-2 and -14 increases with stretching and are normally regulated by mTOR [9].
• Increased platelet aggregation and activity of MMP-2 would alter platelet-platelet and platelet-vessel wall interactions, contributing to an exaggerated response to injury with loss of ovarian hormones [10].
• Pretreatment of the GP-TSMC with the bradykinin B2 receptor (BKB2-R) antagonist Hpp-HOE-140 (Hpp-D-Arg0-Hyp3-Thi5-D-Tic7-Oic8-BK; 10(-8)-10(-4) M) significantly inhibited the BK-stimulated upregulation of MMP-2 in GP-TSMC in a concentration-related manner [11].
• Only at luteolysis (day 17), Ca++/Mg++-dependent endonuclease and MMP-2 spontaneous activity increased significantly [12].

Anatomical context of MMP-2

• These results provide the first evidence for the involvement of BK in the release of MMP-2 from airway smooth muscle cells through activation of the BKB2-R [11].
• Likewise, inhibitor activity against MMP-2 in the uterine cervix was enhanced in response to relaxin (P < 0.05) [13].
• Expression of 72-kDa gelatinase (MMP-2), collagenase (MMP-1), and tissue metalloproteinase inhibitor (TIMP) in primary pig skin fibroblast cultures derived from radiation-induced skin fibrosis [14].
• Specific localization of MMP-2 and -9 transcripts above background was not observed by in situ hybridization in either embryos or uterus [15].
• RESULTS: Pressure distention irreversibly overstretched the porcine jugular vein and increased MMP-2 and MMP-9 proteolytic activity by 40% and 77%, respectively [16].

Associations of MMP-2 with chemical compounds

• MMP-2 also had pyrimidine tracts in the extreme 5' region of its UTR [9].
• The wortmannin sensitivity implicates phosphoinositide 3-kinase as a modulator of the MMP-2 but not the MMP-14 increase [9].
• Treatment with LY-294002 selectively reduced active MMP-2 in media samples according to zymography and Western blot analysis without concomitant changes in latent MMP-2 [1].
• We conclude that acetaminophen is cardioprotective, at least in part, by attenuating peroxynitrite-activated, MMP-2-mediated cleavage of TnI [2].
• Western blotting and gel zymography revealed higher 72 kDa (pro-MMP-2) proteolytic activity in heart homogenates of vehicle-treated versus acetaminophen-treated hearts [2].

Other interactions of MMP-2

• Wortmannin blocked the MMP-2 but not the MMP-14 increase [9].
• Molecular analysis using reverse transcription-polymerase chain reaction, Western immunoblotting, gelatin zymography, and reverse zymography were performed to study the expression and activation of MMP-2 and MMP-9, and tissue inhibitors of MMP (TIMP)-1 and TIMP-2 [16].
• Inhibitor activity in uterine tissue extracts and uterine flushes from relaxin-treated animals was greater than that in controls; however, this activity was restricted to inhibition of MMP-2 [13].
• After 1 month, the specimens were rapidly thawed (37 degrees C) and processed for biomechanical, ultrastructural, morphological and immunohistochemical (MMP-1, MMP-2, MMP-3 and MMP-9) analysis [17].
• The matrix metalloproteinase-9 (MMP-9) activity increased by 30, 46, 12 and 23% after 3, 24, 48 and 72 h of HN2 exposure, respectively, whereas the MMP-2 was elevated by 8, 65, 8 and 30%, respectively [18].

Analytical, diagnostic and therapeutic context of MMP-2

• METHODS: Porcine TM cells were subjected to mechanical stretching, and changes in MMP-2 and -14 levels were determined by gelatin zymography and Western immunoblot analysis [9].
• The furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone did not prevent MMP-2 activation after balloon angioplasty [1].
• METHODS: In a porcine model of isolated-reperfused lung, we studied the alveolar-capillary permeability and the zymographic expression of MMP-9 and MMP-2 in the bronchoalveolar lavage fluid of lungs submitted ex vivo to ischemia in three preservation solutions [modified Euro-Collins (EC), low-potassium-dextran, modified-blood] [19].
• BACKGROUND: We hypothesized the source of early proliferating cells contributing to venous stenosis formation in a porcine hemodialysis grafts is the adventitia and media, and migration of these cells is greatest within the first two weeks following graft placement, resulting in increased matrix metalloproteinase-2 (MMP-2) activity [3].
• MMP-2 mRNA expression was evaluated by quantitative real-time PCR [20].

References