Abstract | OBJECTIVE: METHODS AND RESULTS:
GX sPLA(2) was detected by immunostaining in human aneurysmal tissue and in angiotensin II (Ang II)-induced AAAs in apolipoprotein E-deficient ( apoE(-/-)) mice. GX sPLA(2) mRNA was increased significantly (11-fold) in abdominal aortas of apoE(-/-) mice in response to Ang II infusion. To define the role of GX sPLA(2) in experimental AAAs, apoE(-/-) and apoE(-/-) x GX sPLA(2)(-/-) (GX DKO) mice were infused with Ang II for either 10 (n=7) or 28 (n=24-26) days. Deficiency of GX sPLA(2) significantly reduced the incidence and severity of AAAs, as assessed by ultrasound measurements in vivo of aortic lumens and by computer-assisted morphometric analyses ex vivo of external diameter. Results from gene expression profiling indicated that the expression of specific matrix metalloproteinases and inflammatory mediators was blunted in aortas from GX DKO mice compared to apoE(-/-) mice after 10-day Ang II infusion. Ang II induction of cyclooxygenase-2, interleukin-6, matrix metalloproteinase (MMP)-2, MMP-13 and MMP-14 was reduced significantly in GX DKO mice compared to apoE(-/-) mice. CONCLUSION:
GX sPLA(2) promotes Ang II-induced pathological responses leading to AAA formation.
|
Authors | Melissa Zack, Boris B Boyanovsky, Preetha Shridas, William Bailey, Kathy Forrest, Deborah A Howatt, Michael H Gelb, Frederick C de Beer, Alan Daugherty, Nancy R Webb |
Journal | Atherosclerosis
(Atherosclerosis)
Vol. 214
Issue 1
Pg. 58-64
(Jan 2011)
ISSN: 1879-1484 [Electronic] Ireland |
PMID | 20833395
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
|
Copyright | Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Apolipoproteins E
- Interleukins
- Angiotensin II
- Group X Phospholipases A2
- PLA2G10 protein, human
- Pla2g10 protein, mouse
- Metalloproteases
|
Topics |
- Angiotensin II
(metabolism)
- Animals
- Aorta, Abdominal
(pathology)
- Aortic Aneurysm, Abdominal
(metabolism)
- Apolipoproteins E
(genetics, metabolism)
- Blood Pressure
- Group X Phospholipases A2
(metabolism)
- Humans
- Inflammation
- Interleukins
(metabolism)
- Metalloproteases
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
|