Bone marrow-derived MCP1 required for experimental aortic aneurysm formation and smooth muscle phenotypic modulation

Area of Science:

• Cardiovascular Biology
• Immunology
• Vascular Biology

Background:

• Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by aortic dilation.
• The role of monocyte chemotactic protein 1 (MCP1) in AAA pathogenesis and smooth muscle cell (SMC) modulation remains incompletely understood.

Purpose of the Study:

• To investigate the necessity of MCP1 for AAA formation and SMC phenotypic modulation in a mouse elastase perfusion model.
• To determine the cellular source of MCP1 contributing to AAA development.

Main Methods:

• Analysis of infrarenal aortas from wild-type (WT) and MCP1 knockout (KO) mice after elastase perfusion.
• Identification of MCP1 cellular sources using bone marrow transplantation.
• In vitro assessment of MCP1's direct effects on cultured aortic SMCs, including contractile protein expression and matrix metalloproteinase (MMP) production.

Main Results:

• MCP1 KO mice exhibited significantly reduced aortic dilation (53.7%) compared to WT mice (102%) after elastase perfusion.
• MCP1 deficiency led to preserved differentiated smooth muscle, intact elastic fibers, and reduced MMP2 levels in aortic media.
• Bone marrow-derived MCP1 was identified as the primary driver of AAA formation, with selective KO in bone marrow cells offering greater protection than global KO.

Conclusions:

• MCP1 derived from bone marrow cells is essential for experimental AAA formation.
• MCP1 directly impacts SMCs, repressing contractile proteins and inducing MMPs, thereby contributing to AAA pathogenesis.
• Targeting bone marrow-derived MCP1 represents a potential therapeutic strategy for AAA.