Imatinib prevents elastase-induced abdominal aortic aneurysm progression by regulating macrophage-derived MMP9

Area of Science:

• Cardiovascular Research
• Pharmacology
• Molecular Biology

Background:

• Abdominal aortic aneurysm (AAA) involves aortic wall weakening and dilation, with no current pharmacological treatments.
• Macrophage-derived matrix metalloproteinase-9 (MMP9) is critical in extracellular matrix degradation, driving AAA development and rupture.

Purpose of the Study:

• To investigate the therapeutic potential of Imatinib in mitigating AAA progression.
• To elucidate the molecular mechanisms underlying Imatinib's effects on MMP9 expression and activity in AAA.

Main Methods:

• In vitro studies assessed Imatinib's effect on MMP9 transcription, protein expression, and secretion in macrophages.
• In vivo studies utilized an elastase-induced rat AAA model treated with Imatinib to evaluate its impact on aneurysm progression and survival.
• Immunohistochemistry and zymography were employed to assess MMP9 expression and activity in aortic tissues.

Main Results:

• Imatinib suppressed MMP9 transcription, protein levels, and secretion in macrophages in a dose-dependent manner.
• In vivo, Imatinib stabilized AAA progression, reduced aortic diameter, prevented elastin degradation, and improved survival rates.
• Imatinib significantly inhibited MMP9 expression and activity in aortic tissues without affecting macrophage infiltration.
• The drug reduced STAT3 phosphorylation and nuclear translocation, thereby inhibiting MMP9 transcription.

Conclusions:

• Imatinib prevents AAA progression by inhibiting STAT3-mediated MMP9 expression and activation.
• These findings suggest Imatinib as a potential novel therapeutic agent for clinical treatment of abdominal aortic aneurysms.