Plasminogen activator expression in human atherosclerotic lesions

Area of Science:

• Cardiovascular Biology
• Molecular Pathology
• Proteolysis

Background:

• The plasminogen activator (PA) system influences atherosclerosis by affecting fibrin and matrix turnover and cell migration.
• Understanding PA roles in atherosclerotic lesions is crucial for developing therapeutic strategies.

Purpose of the Study:

• To analyze the expression and activity of tissue-type PA (tPA) and urokinase-type PA (uPA) in normal and atherosclerotic arteries.
• To investigate the localization of PAs within atherosclerotic plaques and their association with cellular and matrix components.

Main Methods:

• In situ hybridization for mRNA detection.
• Immunohistochemistry for antigen localization.
• Histoenzymology and zymography for enzymatic activity assessment.
• Double immunofluorescence and confocal microscopy for colocalization studies.

Main Results:

• tPA and uPA mRNA and antigen were found in endothelial cells and smooth muscle cells (SMCs) in normal arteries.
• Atherosclerotic lesions showed increased tPA in SMCs and foam cells, and uPA in macrophages and SMCs.
• uPA-dependent lytic activity was detected in advanced lesions, while normal arteries showed mainly tPA-dependent activity.
• Both tPA and uPA were present in neomicrovessels, suggesting a role in plaque angiogenesis.

Conclusions:

• A dynamic, local PA-dependent proteolytic process occurs in atherosclerotic lesion areas, involving macrophages and SMCs.
• PA expression and activity are significantly altered in atherosclerosis, particularly in advanced lesions.
• Understanding these proteolytic mechanisms may lead to new therapies for plaque stabilization.