DOCK2 Deficiency Attenuates Abdominal Aortic Aneurysm Formation-Brief Report

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Vascular Biology

Background:

• Abdominal aortic aneurysm (AAA) is a life-threatening condition lacking effective pharmacological treatments.
• Elastin laminae degradation is a key factor in AAA development.
• The role of dedicator of cytokinesis 2 (DOCK2) in AAA pathogenesis is currently unknown.

Purpose of the Study:

• To investigate the role of DOCK2 in the formation and development of abdominal aortic aneurysms (AAA).
• To elucidate the molecular mechanisms by which DOCK2 influences AAA progression.

Main Methods:

• Utilized angiotensin II (Ang II) infusion in apolipoprotein E-deficient (ApoE-/-) mice and topical elastase-induced AAA models in DOCK2 knockout (DOCK2-/-) mice.
• Examined human AAA specimens to assess the relevance of DOCK2 in human disease.
• Analyzed elastin fragmentation via elastin staining and matrix metalloproteinase (MMP) activity using in situ zymography.

Main Results:

• DOCK2 expression was significantly elevated in AAA lesions from both mouse models and human samples.
• DOCK2 deficiency markedly reduced AAA formation, dissection, and rupture in mice.
• DOCK2 knockout led to decreased expression and activity of monocyte chemoattractant protein-1 (MCP-1) and MMPs, thereby attenuating elastin degradation.

Conclusions:

• DOCK2 acts as a novel regulator in the development of abdominal aortic aneurysms.
• DOCK2 promotes AAA formation by upregulating MCP-1 and MMP2, driving vascular inflammation and elastin degradation.