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

30 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

  • Cardiology and Cardiovascular Medicine
  • Surgery

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