Macrophage activation promotes major inflammatory disorders, including arterial diseases. Its underlying mechanisms, however, remain obscure. The present study will establish a systems approach, involving computational prediction analyses, multi-omics, network science, and in vitro and in vivo validation, to discover long noncoding RNA (lncRNA)-mediated mechanisms for pro-inflammatory activation of macrophages and arterial disease.
In Specific Aim 1, we will involve omics studies of human macrophages to identify lncRNAs and their interacting proteins and develop computational analyses to predict human lncRNAs that regulate macrophage activation.
Specific Aim 2 will examine the functionality of candidate lncRNAs in macrophage activation in vitro and in vivo. The findings from the study will help to identify new mechanisms for macrophage activation and may provide molecular bases for new therapies.
Inflammation plays a key role in coronary artery disease and other major vascular diseases, global health threats. Even with potent risk modifiers, e.g., statins, many patients still suffer vascular events. Long noncoding RNAs (lncRNAs) regulate various biological processes. We aim to discover lncRNAs that promotes vascular inflammation. The potential outcomes will offer new targets for much needed therapies for vascular diseases.