Age-related differences in serum MFG-E8, TGF-β1 and correlation to the severity of atherosclerosis determined by ultrasound

Abstract

Atherosclerosis (AS) is an age‑related inflammatory disease. Globule‑epidermal growth factor‑8 (MFG‑E8) and transforming growth factor-β1 (TGF‑β1) are involved in the pathogenesis of AS. However, age‑related changes in circulating levels of MFG‑E8 and TGF‑β1, and their correlation with the severity of AS is not well‑characterized. In this study, we investigated age‑related changes in serum levels of MFG‑E8, TGF‑β1 and examined their association with the severity of AS. Sixty healthy volunteers were divided into young, middle‑age and old‑age groups. In addition, carotid ultrasound examination was performed to assess the intima‑media thickness (IMT) of carotid artery. Sixty‑seven patients with carotid AS and 30 age‑matched healthy persons were divided into IMT increased group, plaque group and control group. Serum levels of MFG‑E8, TGF‑β1, tumor necrosis factor-α (TNF‑α) and intercellular adhesion molecule‑1 were measured in all subjects. A positive association between serum MFG‑E8 levels and age was observed in healthy volunteers, while a significant negative association was observed between TGF‑β1 levels and age. Serum levels of MFG‑E8 and TNF‑α showed a positive correlation while those of TGF‑β1 showed a negative correlation with Crouse scores for carotid artery IMT (P<0.05 for both). Both MFG‑E8 and TGF‑β1 were age‑related inflammatory factors. MFG‑E8 showed a positive correlation, while TGF‑β1 showed a negative correlation with the severity of AS. Our findings suggest that both MFG‑E8 and TGF‑β1 are age‑related inflammatory factors and are related to the degree of AS. In conclusion, both MFG‑E8 and TGF‑β1 may serve as potential markers of the severity of AS.

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome

“…In contrast, because adiponectin and leptin are adipokines closely linked to lipid metabolism, these markers had a lower correlation with glucose level [ 8 ], which is the major component of metabolic syndrome. MFG-E8 also had a significant association with pulse wave velocity in this study, which is in accordance with the results of previous studies, suggesting that MFG-E8 could be a promising diagnostic biomarker in vascular disease [ 19 - 22 ]. It is suggested that MFG-E8 cause an age-associated increase in extracellular matrix adhesion molecules.…”

The Inflammatory Role of Milk Fat Globule Epidermal Growth Factor VIII in Angiotensin II Induced Arterial Remodeling

“…When WT mice were infused with Ang II, NF-кB was 32 markedly increased in WT but not in KO, suggesting that MFG-E8 is an important intermediary of NF-кB signaling. Several studies indicate that NF-кB activation facilitates the production of MCP1, TNF-α, ICAM1, and VCAM1 during the processes of arterial inflammation and remodeling 14,23-25,33-37 . The upregulation of MCP1 and TNF-α is higher in WT mice than in KO suggesting MFG-E8 involvement.…”

“…It is also known to be involved in inflammatory vascular conditions 7-13 . Prior in vivo studies have demonstrated that the MFG-E8 protein increases during arterial aging and arterial injury, and in hypertensive, diabetic, and atherosclerotic arterial walls 7-12,14 . Additionally, MFG-E8 is a pivotal relay element within the Ang II/monocyte chemoattractant protein-1 (MCP1) signaling cascade that mediates VSMC proinflammation, invasion and proliferation 7,8 .…”

MFGE8, ALB, APOB, APOE, SAA1, A2M, and C3 as Novel Biomarkers for Stress Cardiomyopathy

“…MFGE8, a secreted glycoprotein, is associated with a variety of pathophysiological processes, including anti-inflammatory [11], antifibrosis [12], antiatherosclerosis [13], and inhibition of cardiac hypertrophy [14]. Recent studies have shown that MFGE8 is a part of the arterial inflammatory signaling network that promotes endothelial cell apoptosis [15].…”