Personalized Early-Warning Signals during Progression of Human Coronary Atherosclerosis by Landscape Dynamic Network Biomarker.

Jing Ge,Jingzhou Chen,Chengming Zhang,Chenxi Song,Luonan Chen,Xiaoping Liu,Kefei Dou

doi:10.3390/genes11060676

Abstract

Coronary atherosclerosis is one of the major factors causing cardiovascular diseases. However, identifying the tipping point (predisease state of disease) and detecting early-warning signals of human coronary atherosclerosis for individual patients are still great challenges. The landscape dynamic network biomarkers (l-DNB) methodology is based on the theory of dynamic network biomarkers (DNBs), and can use only one-sample omics data to identify the tipping point of complex diseases, such as coronary atherosclerosis. Based on the l-DNB methodology, by using the metabolomics data of plasma of patients with coronary atherosclerosis at different stages, we accurately detected the early-warning signals of each patient. Moreover, we also discovered a group of dynamic network biomarkers (DNBs) which play key roles in driving the progression of the disease. Our study provides a new insight into the individualized early diagnosis of coronary atherosclerosis and may contribute to the development of personalized medicine.

Highlights

Cardiovascular diseases (CVDs) are the leading cause of mortality in the world, accounting for almost one-third of deaths worldwide [1]
Based on the dynamic evolution characteristics of complex disease, we developed the theory of dynamic network biomarkers (DNBs) to identify the tipping point and leading molecular networks during the progression of a complex disease [11], which has been successfully applied in many diseases [12,13]
Through the pathway enrichment analysis of these DNB molecules (Figure 3d), we found that these molecules were mainly enriched in pathways related to lipid metabolism, fatty acid metabolism and amino acid metabolism, which implied that these enriched metabolic pathways played important roles at the tipping point of human coronary atherosclerosis

Summary

Introduction

Cardiovascular diseases (CVDs) are the leading cause of mortality in the world, accounting for almost one-third of deaths worldwide [1]. Among the deaths caused by CVDs, ischemic heart disease accounted for 42.5%, and the primary cause is coronary atherosclerosis [1,2]. Coronary atherosclerosis begins with intimal hyperplasia near the bifurcation of the coronary artery, and causes stenosis or obstruction of the vascular lumen, eventually leading to fatal cardiovascular events such as myocardial infarction [3,4]. Visual stenosis of 50–70% by coronary angiography was defined as the critical lesion of coronary atherosclerosis, which is a common pathological phenotype of the disease [5,6]. The degree of coronary stenosis in patients with critical lesions is similar, the prognosis varies greatly. It is extremely important to develop novel methods and biomarkers to make risk stratification more accurate and identify patients at high risk of adverse events as early as possible

Methods

Results

Conclusion