Related Experiment Video
Updated: Aug 25, 2025
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
Influence of Shear Stress, Inflammation and BRD4 Inhibition on Human Endothelial Cells: A Holistic Proteomic Approach
Johannes Jarausch1,2, Lisa Neuenroth1, Reiner Andag1
1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany.
Insights
This study reveals how inflammation, shear stress, and BET inhibitors impact endothelial cells. BET inhibitor JQ1 demonstrated the most significant changes in protein expression, offering therapeutic potential for atherosclerosis.
Area of Science:
- Proteomics
- Molecular Biology
- Cardiovascular Research
Background:
- Atherosclerosis, a major cardiovascular disease risk factor, is exacerbated by high lipids, irregular shear stress, and inflammation.
- Bromo- and extra-terminal domain (BET) protein inhibitors (BETi) present a potential therapeutic strategy due to their epigenetic and anti-inflammatory actions.
Purpose of the Study:
- To investigate the effects of laminar shear stress, inflammation (TNFα), and a BET inhibitor (JQ1) on human endothelial cells.
- To establish a comprehensive proteomic database detailing these cellular responses.
Main Methods:
- Primary human umbilical cord vascular endothelial cells were utilized.
- Cells were subjected to inflammation (TNFα) and laminar shear stress, with and without the BRD4 inhibitor JQ1.
- Global protein expression profiling was performed using ion mobility separation-enhanced data independent acquisition mass spectrometry (IMS-DIA-MS).
Main Results:
- IMS-DIA-MS identified over 4037 proteins in endothelial cells.
- Inflammation, shear stress, and BETi treatment induced significant alterations in protein expression patterns.
- The BET inhibitor JQ1 exhibited the most substantial impact on the endothelial proteome.
Conclusions:
- This study provides the first extensive proteomic dataset on primary endothelial cells under conditions relevant to atherosclerosis.
- The findings highlight the significant influence of shear stress, inflammation, and BET inhibition on endothelial cell protein expression.
- The results support the investigation of BET inhibitors as a therapeutic approach for cardiovascular diseases.
Abstract:
Atherosclerosis is an important risk factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger atherosclerosis. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their epigenetic mechanism and anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi treatment on human endothelial cells was investigated using global protein expression profiling by ion mobility separation-enhanced data independent acquisition mass spectrometry (IMS-DIA-MS). For this purpose, primary human umbilical cord derived vascular endothelial cells were treated with TNFα to mimic inflammation and exposed to laminar shear stress in the presence or absence of the BRD4 inhibitor JQ1. IMS-DIA-MS detected over 4037 proteins expressed in endothelial cells. Inflammation, shear stress and BETi led to pronounced changes in protein expression patterns with JQ1 having the greatest effect. To our knowledge, this is the first proteomics study on primary endothelial cells, which provides an extensive database for the effects of shear stress, inflammation and BETi on the endothelial proteome.
