TY - JOUR
T1 - Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin
AU - Airhart, Nathan
AU - Brownstein, Bernard H.
AU - Cobb, J. Perren
AU - Schierding, William
AU - Arif, Batool
AU - Ennis, Terri L.
AU - Thompson, Robert W.
AU - Curci, John A.
N1 - Funding Information:
This study was supported by the Flight Attendants Medical Research Institute (J.A.C.), American Heart Association 0765432Z (J.A.C.), the National Heart, Lung and Blood Institute K08-HL-84004 (J.A.C.) and P50-HL-083762 (R.T.), the Society for Vascular Surgery Foundation (J.A.C.), the American College of Surgeons (J.A.C.), the National Institute of Aging R01-AG-037120 (J.A.C.), and the Department of Veterans Affairs (J.A.C.).
Publisher Copyright:
© 2014 Society for Vascular Surgery.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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 matrixMethods 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 blottingConclusions 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.
AB - 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 matrixMethods 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 blottingConclusions 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.
UR - http://www.scopus.com/inward/record.url?scp=84908242910&partnerID=8YFLogxK
U2 - 10.1016/j.jvs.2013.07.097
DO - 10.1016/j.jvs.2013.07.097
M3 - Article
C2 - 24080131
AN - SCOPUS:84908242910
VL - 60
SP - 1033-1042.e5
JO - Journal of Vascular Surgery
JF - Journal of Vascular Surgery
SN - 0741-5214
IS - 4
ER -