Pericellular plasmin induces smooth muscle cell anoikis

Area of Science:

• Biochemistry
• Cell Biology
• Vascular Biology

Background:

• Smooth muscle cell (SMC) rarefaction contributes to vascular pathologies.
• The plasminogen activation system (PAS) is investigated as a potential extracellular signal regulating SMCs.
• Understanding SMC apoptosis mechanisms is crucial for vascular disease research.

Purpose of the Study:

• To investigate the role of the PAS in inducing pericellular proteolysis and apoptosis of vascular SMCs.
• To elucidate the mechanism by which plasmin generation on the SMC surface triggers anoikis.
• To determine the direct involvement of plasmin in SMC anoikis.

Main Methods:

• Primary cultures of arterial SMCs were utilized.
• Plasmin generation on the cell surface was assessed.
• Effects of plasminogen, tissue-type plasminogen activator (t-PA), epsilon-aminocaproic acid, alpha2-antiplasmin, and MMP inhibitors were evaluated.
• Anoikis induction was studied in isolated SMCs and ex-vivo arterial rings.

Main Results:

• Cell-surface plasmin generation induced SMC retraction, fibronectin fragmentation, and anoikis.
• t-PA mediated cell-bound plasmin generation, dependent on plasminogen binding.
• Epsilon-aminocaproic acid inhibited plasminogen binding, while alpha2-antiplasmin had limited effect on anoikis.
• MMP inhibitors did not prevent anoikis, supporting plasmin's direct role.
• Plasmin directly induced similar changes in SMCs and arterial rings.

Conclusions:

• Pathological anoikis in vascular SMCs can be triggered by the functional assembly of the PAS on the cell surface.
• Cell-surface plasmin directly mediates SMC apoptosis (anoikis) and extracellular matrix degradation.
• This finding highlights a novel mechanism in vascular pathology involving the plasminogen activation system.