Group X secretory phospholipase A2 augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice

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

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Objective: Abdominal aortic aneurysm (AAA) is a complex vascular disease characterized by matrix degradation and inflammation and is a major cause of mortality in older men. Specific interventions that prevent AAA progression remain to be identified. In this study, we tested the hypothesis that Group X secretory phospholipase A 2 (GX sPLA 2), an enzyme implicated in inflammatory processes, mediates AAA. 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.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalAtherosclerosis
Volume214
Issue number1
DOIs
StatePublished - Jan 1 2011

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Group X Phospholipases A2
Abdominal Aortic Aneurysm
Apolipoproteins E
Angiotensin II
Matrix Metalloproteinase 13
Matrix Metalloproteinase 14
Matrix Metalloproteinase 2
Abdominal Aorta
Gene Expression Profiling
Cyclooxygenase 2
Matrix Metalloproteinases
Vascular Diseases
Aorta
Interleukin-6
Inflammation

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Zack, Melissa ; Boyanovsky, Boris B. ; Shridas, Preetha ; Bailey, William ; Forrest, Kathy ; Howatt, Deborah A. ; Gelb, Michael H. ; de Beer, Frederick C. ; Daugherty, Alan ; Webb, Nancy R. / Group X secretory phospholipase A2 augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice. In: Atherosclerosis. 2011 ; Vol. 214, No. 1. pp. 58-64.
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title = "Group X secretory phospholipase A2 augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice",
abstract = "Objective: Abdominal aortic aneurysm (AAA) is a complex vascular disease characterized by matrix degradation and inflammation and is a major cause of mortality in older men. Specific interventions that prevent AAA progression remain to be identified. In this study, we tested the hypothesis that Group X secretory phospholipase A 2 (GX sPLA 2), an enzyme implicated in inflammatory processes, mediates AAA. 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.",
author = "Melissa Zack and Boyanovsky, {Boris B.} and Preetha Shridas and William Bailey and Kathy Forrest and Howatt, {Deborah A.} and Gelb, {Michael H.} and {de Beer}, {Frederick C.} and Alan Daugherty and Webb, {Nancy R.}",
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Zack, M, Boyanovsky, BB, Shridas, P, Bailey, W, Forrest, K, Howatt, DA, Gelb, MH, de Beer, FC, Daugherty, A & Webb, NR 2011, 'Group X secretory phospholipase A2 augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice', Atherosclerosis, vol. 214, no. 1, pp. 58-64. https://doi.org/10.1016/j.atherosclerosis.2010.08.054

Group X secretory phospholipase A2 augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice. / Zack, Melissa; Boyanovsky, Boris B.; Shridas, Preetha; Bailey, William; Forrest, Kathy; Howatt, Deborah A.; Gelb, Michael H.; de Beer, Frederick C.; Daugherty, Alan; Webb, Nancy R.

In: Atherosclerosis, Vol. 214, No. 1, 01.01.2011, p. 58-64.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Group X secretory phospholipase A2 augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice

AU - Zack, Melissa

AU - Boyanovsky, Boris B.

AU - Shridas, Preetha

AU - Bailey, William

AU - Forrest, Kathy

AU - Howatt, Deborah A.

AU - Gelb, Michael H.

AU - de Beer, Frederick C.

AU - Daugherty, Alan

AU - Webb, Nancy R.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Objective: Abdominal aortic aneurysm (AAA) is a complex vascular disease characterized by matrix degradation and inflammation and is a major cause of mortality in older men. Specific interventions that prevent AAA progression remain to be identified. In this study, we tested the hypothesis that Group X secretory phospholipase A 2 (GX sPLA 2), an enzyme implicated in inflammatory processes, mediates AAA. 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.

AB - Objective: Abdominal aortic aneurysm (AAA) is a complex vascular disease characterized by matrix degradation and inflammation and is a major cause of mortality in older men. Specific interventions that prevent AAA progression remain to be identified. In this study, we tested the hypothesis that Group X secretory phospholipase A 2 (GX sPLA 2), an enzyme implicated in inflammatory processes, mediates AAA. 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.

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