Plasminogen activator and plasminogen activator inhibitor expression by normal and aneurysmal human aortic smooth muscle cells in culture

Henk D. Louwrens*, Hau C. Kwaan, William H. Pearce, James S T Yao, Elaine Verrusio

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Objectives: Matrix metalloproteinases may play a major role in aortic wall degeneration causing abdominal aortic aneurysm (AAA). Available plasmin, required for MMP zymogen activation, is regulated by plasminogen activators (uPA, tPA) and plasminogen activator inhibitors (PAI-1, PAI-2). To appraise the impact of these regulatory proteins on aortic wall degeneration, expression at the level of translation and transcription was determined in human aortic smooth muscle cell (SMC) cultures. Methods: Explants were derived from aneurysmal aortic tissue (n = 6) and from three male organ donors. Cells were also stimulated with 0.1-1.0 ng/ml IL-1β. Results: uPA antigen and tPA antigen in the conditioned medium (CM) of normal SMCs were not detectable but AAA SMCs produced uPA (values are given as median (interquartile range)), [1.97 ng/ml/106 cells (1.50-8.21)] and tPA [7.02 ng/ml/106 cells (6.20-14.90)]. uPA antigen was absent from normal SMC cell extract (CE) but present in small amounts in AAA SMC CE [0.80 ng/mg protein (0.40-1.24)]. tPA was detectable in the CE of normal SMCs [3.2 ng/mg protein (1.90-3.40)] but at a lower concentration than in AAA SMCs [13.14 ng/mg protein (7.20-27.00)] (p < 0.05). IL-1β suppressed production of uPA and tPA in both types of SMCs. The difference in baseline PAI-1 release from normal SMCs and AAA SMCs was not statistically significant. Selective upregulation of PAI-1 was observed for AAA SMC after IL-1β stimulation. Northern analysis of AAA SMCs grown in serum containing medium exhibited clear bands for uPA. Conclusions: Human AAA SMCs are a source of elevated plasminogen activators. In the absence of a reciprocal rise of PAI an imbalance is created favouring proteolysis.

Original languageEnglish (US)
Pages (from-to)289-293
Number of pages5
JournalEuropean Journal of Vascular and Endovascular Surgery
Volume10
Issue number3
DOIs
StatePublished - Oct 1995

Keywords

  • Abdominal
  • Aortic aneurysm
  • Interleukin-1β
  • Plasminogen activator
  • Smooth muscle cell

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Plasminogen activator and plasminogen activator inhibitor expression by normal and aneurysmal human aortic smooth muscle cells in culture'. Together they form a unique fingerprint.

Cite this