Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study

Area of Science:

• Cardiovascular Research
• Inflammation Biology
• Biomarker Discovery

Background:

• Atherosclerosis, a primary cause of cardiovascular diseases (CVD), is linked to systemic inflammation.
• Matrix metalloproteinases (MMPs), particularly MMP12, and the SDF1/CXCR4 axis contribute to atherosclerosis by promoting macrophage recruitment.
• New circulatory inflammatory markers require assessment for their role in atherosclerosis progression.

Purpose of the Study:

• To identify novel circulating inflammatory markers associated with atherosclerosis.
• To investigate the relationship between SDF1, MMP12, CRP, and cardiovascular risk.
• To explore the role of the SDF1/CXCR4 axis and MMP12 in atherosclerosis development.

Main Methods:

• Measured SDF1, MMP12, and CRP in 298 patients with cardiovascular risk.
• Utilized RT-qPCR and immunohistochemistry to analyze CXCR4/SDF1 axis and MMP12 expression in mouse models of atherosclerosis (Apoe-/- and Apoe-/-Mmp10-/-).

Main Results:

• SDF1, MMP12, and CRP were initially elevated in patients with clinical atherosclerosis; SDF1 and CRP remained significant after controlling for confounders.
• High levels of SDF1 and CRP increased the risk of clinical atherosclerosis by 2.8-fold (p=0.022).
• Elevated SDF1, MMP12, and CRP correlated with increased mortality risk (HR=3.2, p=0.004).
• Increased aortic expression of CXCR4 and MMP12 was observed in Apoe-/- mice.

Conclusions:

• A combination of high circulating SDF1, MMP12, and CRP identifies patients with significant inflammatory cardiovascular risk and elevated mortality.
• The SDF1/CXCR4 axis and MMP12 are implicated in atherosclerosis development, suggesting their potential as therapeutic targets.