Gelatinase expression and proteolytic activity in giant-cell arteritis

Area of Science:

• Vascular Biology
• Immunology
• Matrix Metalloproteinases

Background:

• Giant-cell arteritis (GCA) is characterized by inflammation of arteries, with gelatinases (matrix metalloproteinases-2 and -9) implicated in vascular damage.
• The activation status and enzymatic activity of these gelatinases in GCA lesions remain largely uncharacterized.

Purpose of the Study:

• To investigate the distribution and proteolytic activity of gelatinases (MMP2 and MMP9) in temporal artery lesions from GCA patients at various disease stages.
• To evaluate the role of MMP activators and inhibitors in modulating gelatinase activity within GCA.

Main Methods:

• Real-time PCR and immunohistochemistry were used to assess the expression of MMP2, MMP9, MMP14, TIMP1, and TIMP2 in temporal artery sections from 46 GCA patients and 12 controls.
• In situ zymography was employed to determine the activation status and enzymatic activity of MMPs.

Main Results:

• GCA lesions exhibited strong expression of active MMP2, MMP9, and MMP14, primarily by infiltrating leukocytes.
• Despite the presence of inhibitors TIMP1 and TIMP2, elevated MMP9/TIMP1 and MMP2/TIMP2 ratios indicated an increased proteolytic balance in GCA patients.
• Maximal gelatinase expression and activity were localized to granulomatous areas around the internal elastic lamina, with myointimal cells also showing proteolytic activity.

Conclusions:

• GCA lesions demonstrate intense gelatinase expression and enhanced proteolytic activity due to regulated activators and inhibitors.
• Gelatinases play a significant role in the inflammatory progression, vessel destruction, and potentially the repair processes in GCA.