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- Title
Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study.
- Authors
Marcos-Jubilar, María; Orbe, Josune; Roncal, Carmen; Machado, Florencio J. D.; Rodriguez, José Antonio; Fernández-Montero, Alejandro; Colina, Inmaculada; Rodil, Raquel; Pastrana, Juan C.; Páramo, José A.; Angiolillo, Antonella
- Abstract
BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. METHODS: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). RESULTS: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5–7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. CONCLUSIONS: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets.
- Subjects
MATRIX metalloproteinases; ETIOLOGY of diseases; ATHEROSCLEROSIS; LABORATORY mice; INFLAMMATION
- Publication
Life (2075-1729), 2021, Vol 11, Issue 5, p414
- ISSN
2075-1729
- Publication type
Article
- DOI
10.3390/life11050414