Deficiency of Endogenous Acute-Phase Serum Amyloid A Protects apoE-/- Mice From Angiotensin II-Induced Abdominal Aortic Aneurysm Formation.

Abstract

OBJECTIVE:

Rupture of abdominal aortic aneurysm (AAA), a major cause of death in the aged population, is characterized by vascular inflammation and matrix degradation. Serum amyloid A (SAA), an acute-phase reactant linked to inflammation and matrix metalloproteinase induction, correlates with aortic dimensions before aneurysm formation in humans. We investigated whether SAA deficiency in mice affects AAA formation during angiotensin II (Ang II) infusion.

APPROACH AND RESULTS:

Plasma SAA increased ≈60-fold in apoE(-/-) mice 24 hours after intraperitoneal Ang II injection (100 μg/kg; n=4) and ≈15-fold after chronic 28-day Ang II infusion (1000 ng/kg per minute; n=9). AAA incidence and severity after 28-day Ang II infusion was significantly reduced in apoE(-/-) mice lacking both acute-phase SAA isoforms (SAAKO; n=20) compared with apoE(-/-) mice (SAAWT; n=20) as assessed by in vivo ultrasound and ex vivo morphometric analyses, despite a significant increase in systolic blood pressure in SAAKO mice compared with SAAWT mice after Ang II infusion. Atherosclerotic lesion area of the aortic arch was similar in SAAKO and SAAWT mice after 28-day Ang II infusion. Immunostaining detected SAA in AAA tissues of Ang II-infused SAAWT mice that colocalized with macrophages, elastin breaks, and enhanced matrix metalloproteinase activity. Matrix metalloproteinase-2 activity was significantly lower in aortas of SAAKO mice compared with SAAWT mice after 10-day Ang II infusion.

CONCLUSIONS:

Lack of endogenous acute-phase SAA protects against experimental AAA through a mechanism that may involve reduced matrix metalloproteinase-2 activity.

• Authors: Nancy R Webb, Maria C De Beer, Joanne M Wroblewski, Ailing Ji, William Bailey, Preetha Shridas, Richard J Charnigo, Victoria P Noffsinger, Jassir Witta, Deborah A Howatt, Anju Balakrishnan, Debra L Rateri, Alan Daugherty, Frederick C De Beer
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 35 Issue 5 Pg. 1156-65 (May 2015) ISSN: 1524-4636 [Electronic] United States
• PMID: 25745063 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Apolipoproteins E
• Biomarkers
• Serum Amyloid A Protein
• Angiotensin II
• Elastin
• Matrix Metalloproteinase 2

Topics

• Angiotensin II (pharmacology)
• Animals
• Aortic Aneurysm, Abdominal (pathology, prevention & control)
• Apolipoproteins E (deficiency)
• Biomarkers (blood)
• Disease Models, Animal
• Elastin (metabolism)
• Macrophages (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Random Allocation
• Sensitivity and Specificity
• Serum Amyloid A Protein (deficiency, metabolism)