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

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.

Novel immune cell infiltration-related biomarkers in atherosclerosis diagnosis

“…As for CHI3L1, it is a risk factor of AS, in which its expression is up-regulated and knockdown of CHI3L1 reduced lipids, macrophages and expressions of local proinflammatory mediators in plaques ( Gong et al, 2014 ). Higher MMP9 and MMP12 expressions were observed in AS patients ( Gong et al, 2014 ; Marcos-Jubilar et al, 2021 ), which is consistent with the public sequencing results. Nuciferine exerts its protective role against AS by Calm4/MMP12/AKT signaling to regulate the migration and proliferation of vascular smooth muscle cells.…”

[Retracted] Predictive Significance of High‐Sensitivity C‐Reactive Protein Combined with Homocysteine for Coronary Heart Disease in Patients with Anxiety Disorders

“…CHD is an important cause of high mortality worldwide. One of the most common causes of CHD is atherosclerosis-related vascular inflammation [ 15 ], and the inhibition of inflammation can significantly reduce the recurrence rate of atherosclerotic diseases [ 16 ]. Currently, inflammatory biomarkers can be used to aid in the detection of cardiovascular diseases and to monitor their evaluation, prognosis, and treatment progress [ 17 , 18 ].…”

Small interfering RNA-induced silencing lncRNA PVT1 inhibits atherosclerosis via inactivating the MAPK/NF-κB pathway

“…AS is considered as an inflammatory disease and lipid metabolism disorder [ 28 ]. MMPs are related to AS progression [ 29 ]. CRP, the representative acute phase protein, is sensitive for inflammation and tissue damage, and its elevated plasma level is correlated with increased risk of cardiovascular diseases [ 30 ].…”