Urokinase-type plasminogen activator deficiency in bone marrow-derived cells augments rupture of angiotensin II-induced abdominal aortic aneurysms

Haruhito A. Uchida, Aruna Poduri, Venkateswaran Subramanian, Lisa A. Cassis, Alan Daugherty

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objective-Abdominal aortic aneurysms (AAAs) are associated with fragmentation of extracellular matrix during development of aortic dilation and rupture. Therefore, it is important to identify specific protease systems involved in extracellular matrix degradation during AAA formation. The present study determined the contribution of the urokinase system to AAA formation and rupture. Methods and results-Angiotensin II (Ang II)-induced AAAs were associated with increased aortic abundance of both urokinase-type plasminogen activator receptor (uPAR) and urokinase-type plasminogen activator (uPA) proteins. However, this increased presence was unrelated to AAA formation because deficiencies of either uPAR or uPA had no effect on either the incidence or size of Ang II-induced AAAs in both normolipidemic mice and low-density lipoprotein receptor -/- mice fed a saturated fat-enriched diet. Although uPA deficiency did not affect development of AAAs, there was an effect of increasing mortality rate from AAA rupture in hypercholesterolemic mice. Bone marrow transplantation demonstrated that enhanced aneurysmal rupture was attributable to deficiency of uPA in leukocytes. uPA deficiency led to an increased propensity for impaired resolution of the thrombotic material within the aneurysmal tissue. Neither uPAR nor uPA deficiency had any effect on Ang II-induced atherosclerosis in low-density lipoprotein receptor -/- mice. Conclusion-The uPA-uPAR axis has no effect on the formation of Ang II-induced AAAs, but uPA deficiency promotes aneurysmal rupture.

Original languageEnglish
Pages (from-to)2845-2852
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 1 2011
Externally publishedYes

Keywords

  • aneurysms
  • angiotensin II
  • atherosclerosis
  • plasminogen activators

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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