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

Overview

Journal Life (Basel)

Specialty Biology

Date 2021 Jun 2

PMID 34062730

Citations 8

Authors

Maria Marcos-Jubilar

Josune Orbe

Carmen Roncal

Florencio J D Machado

Jose Antonio Rodriguez

Alejandro Fernandez-Montero

Inmaculada Colina

Raquel Rodil

Juan C Pastrana

Jose A Paramo

Affiliations

Soon will be listed here.

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 ( 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, 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.

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