Elevated Type II Secretory Phospholipase A2 Increases the Risk of Early Atherosclerosis in Patients with Newly Diagnosed Metabolic Syndrome.

Chang-Qing Sun,Yi-Zhang Lin,Wei-Wei Sun,Zhi-Yuan Song,Chen-Liang Zhang,Ping Zhu,Hao Gao,Chun-Yan Zhong,Hua Xiao

doi:10.1038/srep34929

Abstract

A critical association between type II secretory phospholipase A2 (sPLA2-IIa) and established atherosclerotic cardiovascular disease has been demonstrated. However, the contribution of sPLA2-IIa to early atherosclerosis remains unknown. This study investigated the association between early-stage atherosclerosis and sPLA2-IIa in metabolic syndrome (MetS) patients. One hundred and thirty-six MetS patients and 120 age- and gender-matched subjects without MetS were included. Serum sPLA2-IIa protein levels and activity were measured using commercial kits. Circulating endothelial activation molecules (vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin), and carotid intima-media thickness (cIMT), were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. MetS patients exhibited significantly higher sPLA2-IIa protein and activity levels than the controls. Both correlated positively with fasting blood glucose and waist circumference in MetS patients. Additionally, MetS patients exhibited strikingly higher levels of endothelial activation molecules and increased cIMT than controls. These levels correlated positively with serum sPLA2-IIa protein levels and activity. Moreover, multivariate analysis showed that high sPLA2-IIa protein and activity levels were independent risk factors of early atherosclerosis in MetS patients. This study demonstrates an independent association between early-stage atherosclerosis and increased levels of sPLA2-IIa, implying that increased sPLA2-IIa may predict early-stage atherosclerosis in MetS patients.

Highlights

Platelets, vascular smooth muscle cells and atherosclerotic lesions[10]
The controls and metabolic syndrome (MetS) patients were similar in age (p = 0.441), gender (p = 0.657), educational level (p = 0.673), total cholesterol (TC) (p = 0.406), and smoking history (p = 0.808)
MetS patients had thicker carotid intima-media thickness (cIMT) than controls (p = 0.013) (Table 2). These data suggested that systematic inflammation had occurred in patients with MetS, which accompanied with vascular endothelial dysfunction and early atherosclerosis

Summary

Introduction

Platelets, vascular smooth muscle cells and atherosclerotic lesions[10]. Expression of sPLA2-IIa is up-regulated in response to cytokines such as interferon-γ(IFN-γ), tumour necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and oxidized low-density lipoprotein (LDL)[10,11]. In subjects with low-to-normal LDL levels and no known cardiovascular disease, sPLA2-IIa is a measurable biomarker to assess the prognostic impact of inflammation on the risk of CAD13. In CAD patients, an increase in circulating sPLA2-IIa levels is a significant risk factor of clinical coronary events during follow-up[14,15,16]. Numerous studies have focused on the relationship between sPLA2-IIa and established atherosclerotic cardiovascular disease, the contribution of this enzyme to the early-stage atherosclerosis of MetS patients remains unknown. Previous studies indicated that circulating endothelial activation molecules (i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin)[17,18], and carotid intima-media thickness (cIMT)[19] are indicators of vascular endothelial dysfunction and early-stage atherosclerosis. The present study investigated the association between sPLA2-IIa protein levels and activity, and early-stage atherosclerosis, in MetS patients

Methods

Results

Conclusion