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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Nod1 ligands induce site-specific vascular inflammation.
Hisanori Nishio1, Shunsuke Kanno, Sagano Onoyama
1Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Arteriosclerosis, Thrombosis, and Vascular Biology
|February 19, 2011
Summary
Stimulants targeting nucleotide-binding domain, leucine-rich repeat-containing (NLR) proteins, specifically Nod1 ligand FK565, induced coronary arteritis in mice. This research offers insights into coronary artery disease pathogenesis.
Area of Science:
- Immunology
- Vascular Biology
- Molecular Medicine
Background:
- Nucleotide-binding domain, leucine-rich repeat-containing (NLR) proteins are key regulators of innate immunity.
- Endothelial cells play a critical role in vascular inflammation and disease.
Purpose of the Study:
- To investigate the impact of NLR protein stimulants on human artery endothelial cells and murine arteries.
- To explore the potential of NLR ligands in inducing vascular inflammation.
Main Methods:
- Human coronary artery endothelial cells were stimulated in vitro with NLR and Toll-like receptor ligands.
- Murine models were used to assess the in vivo effects of FK565, a Nod1 ligand.
- Gene expression analysis (microarray) was performed on inflamed tissues.
Main Results:
- NLR and Toll-like receptor ligands increased adhesion molecule expression and cytokine secretion in endothelial cells.
- FK565 induced site-specific inflammation in the aortic root and coronary arteritis/valvulitis in mice.
- Vascular inflammation correlated with sustained expression of pro-inflammatory genes and matrix metallopeptidases.
Conclusions:
- This study established the first animal model of coronary arteritis induced by oral administration of a synthetic Nod1 ligand.
- Nod1 plays a significant role in the development of site-specific vascular inflammation, particularly coronary arteritis.
- These findings may elucidate the pathogenesis and pathophysiology of human coronary artery disease.
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