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The expression and significance of NF-κB, MMP1, and MMP2 in rats with abdominal aortic aneurysm
Corresponding Author(s) : Zhilei Xie
Cellular and Molecular Biology,
Vol. 66 No. 3: Issue 3
Abstract
This study aimed to investigate the expression and significance of NF-κB, matrix metal protein1 (MMP1), and matrix metal protein2 (MMP2) in rats with abdominal aortic aneurysm (AAA). 48 Wistar rats were collected, then they were divided into an experiment group and a control group (n=24). The rats in the experiment group were used to carry out an abdominal aortic aneurysm modeling, while the rats in the control group were infused with a same dose of saline through catheters. qRT-PCR and ELISA were used to detect the expressions of EGF and VEGF-C in skin tissues and mRNA of NF-κB, MMP1, and MMP2 in their abdominal aorta. A vernier caliper was used to measure the diameter of their abdominal aorta. Western blot was used to detect the expressions of NF-κB, MMP1, and MMP2 in their abdominal aorta. In the experiment group, the abdominal aorta of the rats expanded to some extent after they were infused compared to that before they were infused (P< 0.05), and the abdominal aorta of them was significantly larger than that of the rats in the control group. On the 3rd week after modeling, the abdominal aorta of the rats expanded more obviously compared to that after they were infused for a while in the experiment group, and the expansion rate of the diameter was (57.19 ± 4.67)% (P< 0.05). Protein expression levels of NF-κB, MMP1, and MMP2 in the abdominal aorta of the rats increased significantly in the experiment group compared to those of the rats in the control group (P<0.05). The increase of NF-κB, MMP1, and MMP2 may be related to the pathogenesis of abdominal aortic aneurysm in abdominal aortic aneurysm models of rats.
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- Parodi JC, Palmaz JC, Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms. Ann Vasc Surg 2012; 26: 895-905.
- Kamineni R, Heuser RR. Abdominal Aortic Aneurysm. J Interv Cardiol 2004; 17: 437-445.
- Parodi FE, Mao D, Ennis TL, Bartoli MA, Thompson RW. Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-κB. J Vasc surg 2005; 41(3):479-89.
- Saratzis A, Bown MJ, Wild B, Nightingale P, Smith J, Johnson C, Melas N and Kitas GD. Association between seven single nucleotide polymorphisms involved in inflammation and proteolysis and abdominal aortic aneurysm. J Vasc Surg 2015; 61: 1120-1128.
- Gupta S, Gambhir JK, Kalra O, Gautam A, Shukla K, Mehndiratta M, Agarwal S and Shukla R: Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. J Diabetes Complications 27: 548-552, 2013.
- Sorsa T, Tjäderhane L and Salo T: Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 10: 311-318, 2010.
- Brown GT and Murray GI: Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis. J Pathol 237: 273-281, 2015.
- Liu CC, Chang TC, Lin YT, Yu YL, Ko BS, Sung LY and Liou JY: Paracrine regulation of matrix metalloproteinases contributes to cancer cell invasion by hepatocellular carcinoma-secreted 14-3-3σ. Oncotarget 7: 36988, 2016.
- Morris DR, Biros E, Cronin O, Kuivaniemi H and Golledge J: The association of genetic variants of matrix metalloproteinases with abdominal aortic aneurysm: a systematic review and meta-analysis. Heart 100: 295-302, 2014.
- Liu M, Hu Y, Zhang MF, Luo KJ, Xie XY, Wen J, Fu JH and Yang H: MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma. Cancer Lett 377: 97-104, 2016.
- Wang YP, Liu IJ, Chiang CP and Wu HC: Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1. Mol Cancer 12: 109, 2013.
- Li T, Jing J, Sun L, Jiang B, Xin S, Yang J and Yuan Y: TLR4 and MMP2 polymorphisms and their associations with cardiovascular risk factors in susceptibility to aortic aneurysmal diseases. Biosci Rep 39: 2019.
- Gambhir S, Vyas D, Hollis M, Aekka A and Vyas A: Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies. World J Gastroenterol 21: 3174-3183, 2015.
- Dror R, Lederman M, Umezawa K, Barak V, Pe'er J and Chowers I: Characterizing the Involvement of the Nuclear Factor-kappa B (NFκB) Transcription Factor in Uveal Melanoma. Invest Ophthalmol Vis Sci 51: 1811-1816, 2010.
- Yamashiro Y, Papke CL, Kim J, Ringuette LJ, Zhang QJ, Liu ZP, Mirzaei H, Wagenseil JE, Davis EC and Yanagisawa H: Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice. Sci Signal 8: ra105-ra105, 2015.
- Tsai SH, Wang JC, Liao WI, Hsu YJ, Lin CY, Liao MT, Huang PH and Lin SJ: Fucoidan attenuates angiotensin II-induced abdominal aortic aneurysms through the inhibition of c-Jun N-terminal kinase and nuclear factor 펺B activation. J Vasc Surg: S0741521417325053, 2018.
- Gao P, Si J, Yang B and Yu J: Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (AAA) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B). Med Sci Monit 23: 881-888, 2017.
- Salahat S, Soliman A, Mcgloughlin T, et al: Segmentation of Abdominal Aortic Aneurysm (AAA) Based on Topology Prior Model. 2017.
- Folsom AR, Lutsey PL, Klein R, Klein BE and Tang W: Retinal microvascular signs and incidence of abdominal aortic aneurysm: The Atherosclerosis Risk in Communities Study. Ophthalmic Epidemiol: 1-4, 2017.
- Yu M, Chen C, Cao Y and Qi R: Inhibitory effects of doxycycline on the onset and progression of abdominal aortic aneurysm and its related mechanisms. Eur J Pharmacol: S0014299917303722, 2017.
- Bellosta R, Gelpi G, Lomazzi C, Romagnoni C, Castelli P, Trimarchi S and Piffaretti G: Surgical Treatment Of Synchronous Type B Acute Aortic Dissection And Abdominal Aortic Aneurysm. Ann Vasc Surg 49: 107-114, 2019
- Zhang Q, Lenardo MJ and Baltimore D: 30 years of NF-κB: a blossoming of relevance to human pathobiology. Cell 168: 37-57, 2017.
- Zhu J, Liang Y, Yue S, Fan G, Zhang H and Zhang M: Combination of Panaxadiol and Panaxatriol Type Saponins and Ophioponins From Shenmai Formula Attenuates Lipopolysaccharide-induced Inflammatory Injury in Cardiac Microvascular Endothelial Cells by Blocking NF-kappa B Pathway. J Cardiovasc Pharmacol 69: 140, 2017.
- Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Baeuerle PA and Neumeier D: Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest 97: 1715-1722, 1996.
- Åukaszewicz-Zajć…c M, Mroczko B and SÅ‚owik A: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in amyotrophic lateral sclerosis (ALS). J Neural Transm (Vienna) 121: 1387-1397, 2014.
- Geissinger E, Weisser C, Fischer P, Schartl M and Wellbrock C: Autocrine stimulation by osteopontin contributes to antiapoptotic signalling of melanocytes in dermal collagen. Cancer Res 62: 4820-4828, 2002.
- Lu JG, Li Y, Li L and Kan X: Overexpression of osteopontin and integrin αv in laryngeal and hypopharyngeal carcinomas associated with differentiation and metastasis. J Cancer Res Clin Oncol 137: 1613-1618, 2011.
- Liu LQ, Chen ZW and Yi SJ: Association between the expression of MMP1 gene and prognosis in head and neck squamous cell carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 32: 287-291, 2018.
- Ye S, Dhillon S, Turner SJ, Bateman AC, Theaker JM, Pickering RM, Day I and Howell WM: Invasiveness of Cutaneous Malignant Melanoma Is Influenced by Matrix Metalloproteinase 1 Gene Polymorphism. Cancer Res 61: 1296-1298, 2001.
- Grzelczyk WL, Szemraj J and Józefowicz-KorczyÅ„ska M: The matrix metalloproteinase in larynx cancer. Postepy Hig Med Dosw (Online) 70: 1190, 2016.
- Wilson WR, Anderton M, Choke EC, Dawson J, Loftus IM and Thompson MM: Elevated Plasma MMP1 and MMP9 are Associated with Abdominal Aortic Aneurysm Rupture. Eur J Vasc Endovasc Surg 35: 580-584, 2008.
- Sinha I, Hannawa KK, Eliason JL, Ailawadi G, Deogracias MP, Bethi S, Ford JW, Roelofs KJ, Grigoryants V, Henke PK, et al: Early MT-1 MMP expression following elastase exposure is associated with increased cleaved MMP-2 activity in experimental rodent aortic aneurysms. Surgery 136: 176-182, 2004.
- Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM and Powell JT: Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 15: 1145-1151, 1995.
- Parodi FE, Mao D, Ennis TL, Bartoli MA and Thompson RW: Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-kappaB. J Vasc Surg 41: 479-489, 2005.
References
Parodi JC, Palmaz JC, Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms. Ann Vasc Surg 2012; 26: 895-905.
Kamineni R, Heuser RR. Abdominal Aortic Aneurysm. J Interv Cardiol 2004; 17: 437-445.
Parodi FE, Mao D, Ennis TL, Bartoli MA, Thompson RW. Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-κB. J Vasc surg 2005; 41(3):479-89.
Saratzis A, Bown MJ, Wild B, Nightingale P, Smith J, Johnson C, Melas N and Kitas GD. Association between seven single nucleotide polymorphisms involved in inflammation and proteolysis and abdominal aortic aneurysm. J Vasc Surg 2015; 61: 1120-1128.
Gupta S, Gambhir JK, Kalra O, Gautam A, Shukla K, Mehndiratta M, Agarwal S and Shukla R: Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. J Diabetes Complications 27: 548-552, 2013.
Sorsa T, Tjäderhane L and Salo T: Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 10: 311-318, 2010.
Brown GT and Murray GI: Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis. J Pathol 237: 273-281, 2015.
Liu CC, Chang TC, Lin YT, Yu YL, Ko BS, Sung LY and Liou JY: Paracrine regulation of matrix metalloproteinases contributes to cancer cell invasion by hepatocellular carcinoma-secreted 14-3-3σ. Oncotarget 7: 36988, 2016.
Morris DR, Biros E, Cronin O, Kuivaniemi H and Golledge J: The association of genetic variants of matrix metalloproteinases with abdominal aortic aneurysm: a systematic review and meta-analysis. Heart 100: 295-302, 2014.
Liu M, Hu Y, Zhang MF, Luo KJ, Xie XY, Wen J, Fu JH and Yang H: MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma. Cancer Lett 377: 97-104, 2016.
Wang YP, Liu IJ, Chiang CP and Wu HC: Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1. Mol Cancer 12: 109, 2013.
Li T, Jing J, Sun L, Jiang B, Xin S, Yang J and Yuan Y: TLR4 and MMP2 polymorphisms and their associations with cardiovascular risk factors in susceptibility to aortic aneurysmal diseases. Biosci Rep 39: 2019.
Gambhir S, Vyas D, Hollis M, Aekka A and Vyas A: Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies. World J Gastroenterol 21: 3174-3183, 2015.
Dror R, Lederman M, Umezawa K, Barak V, Pe'er J and Chowers I: Characterizing the Involvement of the Nuclear Factor-kappa B (NFκB) Transcription Factor in Uveal Melanoma. Invest Ophthalmol Vis Sci 51: 1811-1816, 2010.
Yamashiro Y, Papke CL, Kim J, Ringuette LJ, Zhang QJ, Liu ZP, Mirzaei H, Wagenseil JE, Davis EC and Yanagisawa H: Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice. Sci Signal 8: ra105-ra105, 2015.
Tsai SH, Wang JC, Liao WI, Hsu YJ, Lin CY, Liao MT, Huang PH and Lin SJ: Fucoidan attenuates angiotensin II-induced abdominal aortic aneurysms through the inhibition of c-Jun N-terminal kinase and nuclear factor 펺B activation. J Vasc Surg: S0741521417325053, 2018.
Gao P, Si J, Yang B and Yu J: Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (AAA) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B). Med Sci Monit 23: 881-888, 2017.
Salahat S, Soliman A, Mcgloughlin T, et al: Segmentation of Abdominal Aortic Aneurysm (AAA) Based on Topology Prior Model. 2017.
Folsom AR, Lutsey PL, Klein R, Klein BE and Tang W: Retinal microvascular signs and incidence of abdominal aortic aneurysm: The Atherosclerosis Risk in Communities Study. Ophthalmic Epidemiol: 1-4, 2017.
Yu M, Chen C, Cao Y and Qi R: Inhibitory effects of doxycycline on the onset and progression of abdominal aortic aneurysm and its related mechanisms. Eur J Pharmacol: S0014299917303722, 2017.
Bellosta R, Gelpi G, Lomazzi C, Romagnoni C, Castelli P, Trimarchi S and Piffaretti G: Surgical Treatment Of Synchronous Type B Acute Aortic Dissection And Abdominal Aortic Aneurysm. Ann Vasc Surg 49: 107-114, 2019
Zhang Q, Lenardo MJ and Baltimore D: 30 years of NF-κB: a blossoming of relevance to human pathobiology. Cell 168: 37-57, 2017.
Zhu J, Liang Y, Yue S, Fan G, Zhang H and Zhang M: Combination of Panaxadiol and Panaxatriol Type Saponins and Ophioponins From Shenmai Formula Attenuates Lipopolysaccharide-induced Inflammatory Injury in Cardiac Microvascular Endothelial Cells by Blocking NF-kappa B Pathway. J Cardiovasc Pharmacol 69: 140, 2017.
Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Baeuerle PA and Neumeier D: Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest 97: 1715-1722, 1996.
Åukaszewicz-Zajć…c M, Mroczko B and SÅ‚owik A: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in amyotrophic lateral sclerosis (ALS). J Neural Transm (Vienna) 121: 1387-1397, 2014.
Geissinger E, Weisser C, Fischer P, Schartl M and Wellbrock C: Autocrine stimulation by osteopontin contributes to antiapoptotic signalling of melanocytes in dermal collagen. Cancer Res 62: 4820-4828, 2002.
Lu JG, Li Y, Li L and Kan X: Overexpression of osteopontin and integrin αv in laryngeal and hypopharyngeal carcinomas associated with differentiation and metastasis. J Cancer Res Clin Oncol 137: 1613-1618, 2011.
Liu LQ, Chen ZW and Yi SJ: Association between the expression of MMP1 gene and prognosis in head and neck squamous cell carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 32: 287-291, 2018.
Ye S, Dhillon S, Turner SJ, Bateman AC, Theaker JM, Pickering RM, Day I and Howell WM: Invasiveness of Cutaneous Malignant Melanoma Is Influenced by Matrix Metalloproteinase 1 Gene Polymorphism. Cancer Res 61: 1296-1298, 2001.
Grzelczyk WL, Szemraj J and Józefowicz-KorczyÅ„ska M: The matrix metalloproteinase in larynx cancer. Postepy Hig Med Dosw (Online) 70: 1190, 2016.
Wilson WR, Anderton M, Choke EC, Dawson J, Loftus IM and Thompson MM: Elevated Plasma MMP1 and MMP9 are Associated with Abdominal Aortic Aneurysm Rupture. Eur J Vasc Endovasc Surg 35: 580-584, 2008.
Sinha I, Hannawa KK, Eliason JL, Ailawadi G, Deogracias MP, Bethi S, Ford JW, Roelofs KJ, Grigoryants V, Henke PK, et al: Early MT-1 MMP expression following elastase exposure is associated with increased cleaved MMP-2 activity in experimental rodent aortic aneurysms. Surgery 136: 176-182, 2004.
Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM and Powell JT: Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 15: 1145-1151, 1995.
Parodi FE, Mao D, Ennis TL, Bartoli MA and Thompson RW: Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-kappaB. J Vasc Surg 41: 479-489, 2005.