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.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.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.
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.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.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.
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
SN - 0741-5214
VL - 60
SP - 1033-1042.e5
JO - Journal of Vascular Surgery
JF - Journal of Vascular Surgery
IS - 4
ER -