Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin

Nathan Airhart, Bernard H. Brownstein, J. Perren Cobb, William Schierding, Batool Arif, Terri L. Ennis, Robert W. Thompson, John A. Curci

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Results Each SMC type exhibited a unique gene expression pattern. AAA SMCs had greater elastolytic activity than NAA-SMCs (+68%; P <.001) and CEA-SMCs (+45%; P <.001). Zymography showed an increase of active MMP-2 (62 kD) in media from AAA SMCs. AAA SMCs demonstrated twofold greater expression of MMP-2 messenger (m)RNA (P <.05) and 7.3-fold greater MMP-9 expression (P <.01) than NAA-SMCs. Culture with U937 monocytes caused a synergistic increase of elastolysis by AAA SMCs (41%; P <.001) but not NAA-SMCs or CEA-SMCs (P =.99). Coculture with U937 caused a large increase in MMP-9 mRNA in AAA-SMCs and NAA-SMCs (P <.001). MMP-2 mRNA expression was not affected. Western blots of culture media showed a fourfold increase of MMP-9 (92 kD) protein only in AAA-SMCs/U937 but not in NAA-SMCs/U937 (P <.001) and a large increase in active-MMP2 (62 kD), which was less apparent in NAA-SMCs/U937 media (P <.01).

Background The purpose of this study was to further elucidate the role of the vascular smooth muscle cells (SMCs) in abdominal aortic aneurysm (AAA) disease. We hypothesized that that AAA SMCs are unique and actively participate in the process of degrading the aortic matrix

Methods Whole-genome expression profiles of SMCs from AAAs, nondilated abdominal aorta (NAA), and carotid endarterectomy (CEA) were compared. We quantified elastolytic activity by culturing SMCs in [3H]elastin-coated plates and measuring solubilized tritium in the media after 7 days. Matrix metalloproteinase (MMP)-2 and MMP-9 production was assessed using real-time polymerase chain reaction, zymography, and Western blotting

Conclusions AAA-SMCs have a unique gene expression profile and a proelastolytic phenotype that is augmented by macrophages. This may occur by a failure of post-transcriptional control of MMP-9 synthesis.

Original languageEnglish
Pages (from-to)1033-1042.e5
JournalJournal of Vascular Surgery
Volume60
Issue number4
DOIs
StatePublished - Oct 1 2014

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