Matrix Metalloproteinases in Venous Tissue Remodeling and Varicose Vein Formation

Raffetto, Joseph D.; Khalil, Raouf A.

doi:10.2174/157016108784911957

Cited by 62 publications

(46 citation statements)

References 127 publications

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“…Regulation of MMPs may occur at multiple levels via gene transcription and synthesis of inactive proenzymes, posttranslational activation of proenzymes, or the interaction of secreted MMPs with TIMPs [Raffetto et al, 2008]. Our results showed decreased activation of both MMP-2 and MMP-9 in later time points during neovessel formation.…”

Section: Discussionmentioning

confidence: 54%

Characterization of the Natural History of Extracellular Matrix Production in Tissue-Engineered Vascular Grafts during Neovessel Formation

Naito¹,

Williams-Fritze

Duncan³

et al. 2011

Cells Tissues Organs

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Background: The extracellular matrix (ECM) is a critical determinant of neovessel integrity. Materials and Methods: Thirty-six (polyglycolic acid + polycaprolactone and poly lactic acid) tissue-engineered vascular grafts seeded with syngeneic bone marrow mononuclear cells were implanted as inferior vena cava interposition grafts in C57BL/6 mice. Specimens were characterized using immunohistochemical staining and qPCR for representative ECM components in addition to matrix metalloproteinases (MMPs). Total collagen, elastin, and glycosaminoglycan (GAG) contents were determined. MMP activity was measured using zymography. Results: Collagen production on histology demonstrated an initial increase in type III at 1 week followed by type I production at 2 weeks and type IV at 4 weeks. Gene expression of both type I and type III peaked at 2 weeks, whereas type IV continued to increase over the 4-week period. Histology demonstrated fibrillin-1 deposition at 1 week followed by elastin production at 4 weeks. Elastin gene expression significantly increased at 4 weeks, whereas fibrillin-1 decreased at 4 weeks. GAG demonstrated abundant production at each time point on histology. Gene expression of decorin significantly increased at 4 weeks, whereas versican decreased over time. Biochemical analysis showed that total collagen production was greatest at 2 weeks, and there was a significant increase in elastin and GAG production at 4 weeks. Histological characterization of MMPs showed abundant production of MMP-2 at each time point, while MMP-9 decreased over the 4-week period. Gene expression of MMP-2 significantly increased at 4 weeks, whereas MMP-9 significantly decreased at 4 weeks. Conclusions: ECM production during neovessel formation is characterized by early ECM deposition followed by extensive remodeling.

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Section: Discussionmentioning

confidence: 54%

Characterization of the Natural History of Extracellular Matrix Production in Tissue-Engineered Vascular Grafts during Neovessel Formation

Naito¹,

Williams-Fritze

Duncan³

et al. 2011

Cells Tissues Organs

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“…21 Angiogenesis in uveal melanoma is a strong prognostic factor for metastatic death from uveal melanoma, 22 and MMPs and TIMPs have been found to be involved in angiogenesis in cutaneous and uveal melanoma. 23,24 Expression and activation of MMPs are accomplished by various processes, but the activity of MMPs is mainly modulated by TIMP. The overall activity of MMPs is currently thought to depend upon the balance between activated MMPs and free TIMPs.…”

Section: Discussionmentioning

confidence: 99%

Expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in conjunctival melanomas and clinical implications

et al. 2010

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“…In addition, matrix metalloproteinases (MMPs), a family of proteases as major determinants of venous tissue remodeling, were involved in the continuous turnover of collagen, elastin and other proteins of extracellular matrix (ECM). The effects of MMPs on ECM degradation might result in significant venous tissue remodeling and structural changes in the vein wall, leading to venous dilation and valve dysfunction (Raffetto and Khalil 2008). In the study, miR-202 (target to MMP11) and miR-146b-5p (target to MMP16) might be the regulatory miRNAs associated with MMPs regulation in CVI condition.…”

Section: Go Name Degree Apoptosis 10mentioning

confidence: 79%

MicroRNA Profiling in Great Saphenous Vein Tissues of Patients with Chronic Venous Insufficiency

Cui

Guang

Huang

et al. 2012

Tohoku J. Exp. Med.

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Chronic venous insufficiency (CVI) is a common disease characterized by structural and functional abnormalities of the venous system. Until recently, the pathogenesis of CVI remains largely unknown. MicroRNAs (miRNAs) are a family of endogenous small non-coding RNAs emerged as post-transcriptional gene repressors and play essential roles in diverse pathological processes including vascular disease. However, their roles in CVI have not been elucidated. In this study, we employed oligonucleotide microarrays to perform a genome-wide miRNAs profiling in the great saphenous vein (GSV) tissues of patients with CVI. Our results revealed a total of 14 miRNAs that are expressed differentially in GSV tissues. Among them nine miRNAs were found significantly up-regulated, while five miRNAs were downregulated significantly. Real-time RT-PCR verified statistically consistent expression of three selected miRNAs (miR-34a, miR-155 and miR-202) with microarrays analysis. These three miRNAs, which were described as crucial regulators in many biological processes and vascular diseases, might also play important roles in CVI. Functional annotation of target genes of differentially expressed miRNAs via bioinformatics approaches revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for CVI, including mitogen-activated protein kinase pathways, pathways in cancer, apoptosis, and cell cycle, and p53 signaling pathways. In summary, miRNAs might involve in multiple signaling pathways contributing to the pathological processes of CVI. These data may provide fundamental insights into the molecular basis of CVI, which may aid in designing novel approaches for prevention and treatment of this complex disease.Keywords: bioinformatics; chronic venous insufficiency; great saphenous vein; microarray; microRNA Tohoku J. Exp. Med., 2012 Dec, 228 (4), 341-350. © 2012 Tohoku University Medical Press Chronic venous insufficiency (CVI) is a complex medical condition characterized by structural and functional abnormalities of the venous system, which is commonly seen in humans. CVI is manifested with a range of signs, including varicose veins, trophic skin changes and venous ulcers. It has a considerable socioeconomic impact in many countries due to its high prevalence, cost of investigations and management, deterioration of the quality of life and loss of working days (Rabe and Pannier 2010). To date, in spite of numerous studies on CVI, the etiology and pathogenesis of CVI remains largely unknown.MicroRNAs (miRNAs) are a family of highly conserved, endogenous small non-coding RNAs (19-24nt) that post-transcriptionally repress gene expression via degradation or translational inhibition of their target mRNAs. They play important roles in nearly all physiological and pathological processes, including cell differentiation, proliferation, apoptosis, cardiovascular disease, and human cancers (Bartel 2004). There is mounting evidence suggesting that miRNAs had distinct expression profiles an...

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Matrix Metalloproteinases in Venous Tissue Remodeling and Varicose Vein Formation

Cited by 62 publications

References 127 publications

Characterization of the Natural History of Extracellular Matrix Production in Tissue-Engineered Vascular Grafts during Neovessel Formation

Characterization of the Natural History of Extracellular Matrix Production in Tissue-Engineered Vascular Grafts during Neovessel Formation

Expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in conjunctival melanomas and clinical implications

MicroRNA Profiling in Great Saphenous Vein Tissues of Patients with Chronic Venous Insufficiency

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