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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL149302-02
Application #
9973174
Study Section
Vascular Cell and Molecular Biology Study Section (VCMB)
Program Officer
Chen, Jue
Project Start
2019-07-15
Project End
2023-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115