Abstract
Acute aortic dissection (AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican (a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican.
Article PDF
Similar content being viewed by others
References
Ashlin, T.G., Kwan, A.P., and Ramji, D.P. (2013). Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: Differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17. Cytokine 64, 234–242.
Boerboom, D., Russell, D.L., Richards, J.S., and Sirois, J. (2003). Regulation of transcripts encoding ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs-1) and progesterone receptor by human chorionic gonadotropin in equine preovulatory follicles. J Mol Endocrinol 31, 473–485.
Fang, L., Moore, X.L., Dart, A.M., and Wang, L.M. (2015). Systemic inflammatory response following acute myocardial infarction. J Geriatr Cardiol 12, 305–312.
Guo, D., Hasham, S., Kuang, S.Q., Vaughan, C.J., Boerwinkle, E., Chen, H., Abuelo, D., Dietz, H.C., Basson, C.T., Shete, S.S., and Milewicz, D.M. (2001). Familial thoracic aortic aneurysms and dissections: genetic heterogeneity with a major locus mapping to 5q13–14. Circulation 103, 2461–2468.
Iruela-Arispe, M.L., Carpizo, D., and Luque, A. (2003). ADAMTS1: a matrix metalloprotease with angioinhibitory properties. Ann N YAcad Sci 995, 183–190.
Jonsson-Rylander, A.C., Nilsson, T., Fritsche-Danielson, R., Hammarstrom, A., Behrendt, M., Andersson, J.O., Lindgren, K., Andersson, A.K., Wallbrandt, P., Rosengren, B., Brodin, P., Thelin, A., Westin, A., Hurt-Camejo, E., and Lee-Sogaard, C.H. (2005). Role of ADAMTS-1 in atherosclerosis: remodeling of carotid artery, immunohistochemistry, and proteolysis of versican. Arterioscler Thromb Vasc Biol 25, 180–185.
Kuno, K., Kanada, N., Nakashima, E., Fujiki, F., Ichimura, F., and Matsushima, K. (1997). Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem 272, 556–562.
Kuno, K., Okada, Y., Kawashima, H., Nakamura, H., Miyasaka, M., Ohno, H., and Matsushima, K. (2000). ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan. FEBS Lett 478, 241–245.
Kurihara, T., Shimizu-Hirota, R., Shimoda, M., Adachi, T., Shimizu, H., Weiss, S.J., Itoh, H., Hori, S., Aikawa, N., and Okada, Y. (2012). Neutrophil-derived matrix metalloproteinase 9 triggers acute aortic dissection. Circulation 126, 3070–3080.
Ng, Y.H., Zhu, H., Pallen, C.J., Leung, P.C., and MacCalman, C.D. (2006). Differential effects of interleukin-1beta and transforming growth factor- beta1 on the expression of the inflammation-associated protein, ADAMTS-1, in human decidual stromal cells in vitro. Hum Reprod 21, 1990–1999.
Ren, P., Zhang, L., Xu, G., Palmero, L.C., Albini, P.T., Coselli, J.S., Shen, Y.H., and LeMaire, S.A. (2013). ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections. Ann Thorac Surg 95, 570–577.
Russell, D.L., Doyle, K.M., Ochsner, S.A., Sandy, J.D., and Richards, J.S. (2003). Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. J Biol Chem 278, 42330–42339.
Sabatine, M.S., Ploughman, L., Simonsen, K.L., Iakoubova, O.A., Kirchgessner, T.G., Ranade, K., Tsuchihashi, Z., Zerba, K.E., Long, D.U., Tong, C.H., Packard, C.J., Pfeffer, M.A., Devlin, J.J., Shepherd, J., Campos, H., Sacks, F.M., and Braunwald, E. (2008). Association between ADAMTS1 matrix metalloproteinase gene variation, coronary heart disease, and benefit of statin therapy. Arterioscler Thromb Vasc Biol 28, 562–567.
Sampson, U.K., Norman, P.E., Fowkes, F.G., Aboyans, V., Song, Y., Harrell, F.E., Forouzanfar, M.H., Naghavi, M., Denenberg, J.O., McDermott, M.M., Criqui, M.H., Mensah, G.A., Ezzati, M., and Murray, C. (2014a). Estimation of global and regional incidence and prevalence of abdominal aortic aneurysms 1990 to 2010. Glob Heart 8, 159–170.
Sampson, U.K., Norman, P.E., Fowkes, F.G., Aboyans, V., Song, Y., Harrell, F.E., Forouzanfar, M.H., Naghavi, M., Denenberg, J.O., McDermott, M.M., Criqui, M.H., Mensah, G.A., Ezzati, M., and Murray, C. (2014b). Global and regional burden of aortic dissection and aneurysms. Glob Heart 8, 171–180.
Seidelmann, S.B., Kuo, C., Pleskac, N., Molina, J., Sayers, S., Li, R., Zhou, J., Johnson, P., Braun, K., Chan, C., Teupser, D., Breslow, J.L., Wight, T.N., Tall, A.R., and Welch, C.L. (2008). Athsq1 is an atherosclerosis modifier locus with dramatic effects on lesion area and prominent accumulation of versican. Arterioscler Thromb Vasc Biol 28, 2180–2186.
Theocharis, A.D., Tsolakis, I., Hjerpe, A., and Karamanos, N.K. (2001). Human abdominal aortic aneurysm is characterized by decreased versican concentration and specific downregulation of versican isoform V(0). Atherosclerosis 154, 367–376.
Theocharis, A.D., Tsolakis, I., Hjerpe, A., and Karamanos, N.K. (2003). Versican undergoes specific alterations in the fine molecular structure and organization in human aneurysmal abdominal aortas. Biomed Chromatogr 17, 411–416.
Tieu, B.C., Lee, C., Sun, H., Lejeune, W., Recinos, A., 3rd, Ju, X., Spratt, H., Guo, D.C., Milewicz, D., Tilton, R.G., and Brasier, A.R. (2009). An adventitial IL-6/MCP1 amplification loop accelerates macrophage- mediated vascular inflammation leading to aortic dissection in mice. J Clin Invest 119, 3637–3651.
Wagsater, D., Bjork, H., Zhu, C., Bjorkegren, J., Valen, G., Hamsten, A., and Eriksson, P. (2008). ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of human atherosclerotic plaques. Atherosclerosis 196, 514–522.
Wang, L., Zheng, J., Bai, X., Liu, B., Liu, C.J., Xu, Q., Zhu, Y., Wang, N., Kong, W., and Wang, X. (2009). ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation in balloon- injured rat arteries. Circ Res 104, 688–698.
Wight, T.N., and Merrilees, M.J. (2004). Proteoglycans in atherosclerosis and restenosis: key roles for versican. Circ Res 94, 1158–1167.
Wu, D., Shen, Y.H., Russell, L., Coselli, J.S., and LeMaire, S.A. (2013). Molecular mechanisms of thoracic aortic dissection. J Surq Res 184, 907–924.
Zhang, L., Yu, F., Wang, L., Zheng, J., Du, Y., Huang, Y., Liu, B., Wang, X., and Kong, W. (2015). ADAMTS-7 promotes vascular smooth muscle cells proliferation in vitro and in vivo. Sci China Life Sci 58, 674–681
Zhang, X., Shen, Y.H., and LeMaire, S.A. (2009). Thoracic aortic dissection: are matrix metalloproteinases involved? Vascular 17, 147–157.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at link.springer.com
Electronic supplementary material
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Gao, Y., Wu, W., Yu, C. et al. A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) expression increases in acute aortic dissection. Sci. China Life Sci. 59, 59–67 (2016). https://doi.org/10.1007/s11427-015-4959-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-015-4959-4