Damage to the wall of arterial blood vessels leads to the formation of structures known as neointimal lesions. If these structures do not resolve, they cause narrowing of the blood vessel, which leads to oxygen deprivation in the tissues fed by the blood vessels and subsequent tissue and organ damage.
Manfred Boehm and colleagues, at the National Institutes of Health, Bethesda, have now identified some of the early events that occur immediately after arterial blood vessel damage in the mouse, providing information about a stage of the response to arterial blood vessel injury not previously well understood.
The research appears in the Journal of Clinical Investigation.
In the study, when mouse arterial blood vessels were subject to damage, cells in the blood vessel wall known as vascular smooth muscle cells (VSMCs) upregulated expression of a protein known as RANTES. The RANTES was secreted by the VSMCs and attracted inflammatory cells known as T cells and macrophages to the region of arterial blood vessel damage.
Detailed analysis revealed that VSCM expression of RANTES was triggered by the molecule TNF-alpha and was dependent on the gene regulatory molecules STAT3 and NF-kappa-B. Consistent with this, both mice lacking TNF-alpha and mice lacking STAT3 in VSMCs produced less RANTES after arterial blood vessel damage than did normal mice.
The importance of these data are highlighted and put into the context of the bigger picture of arterial blood vessel damage in an accompanying commentary by Timothy Hla and Myat Lin Oo, at Weill Medical College of Cornell University, New York.
- Jason C. Kovacic, Rohit Gupta, Angela C. Lee, Mingchao Ma, Fang Fang, Claire N. Tolbert, Avram D. Walts, Leilani E. Beltran, Hong San, Guibin Chen, Cynthia St. Hilaire and Manfred Boehm. STAT3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice. Journal of Clinical Investigation, Published December 28, 2009 DOI: 10.1172/JCI40364
- Timothy Hla and Myat Lin Oo. Ramping up RANTES in the acute response to arterial injury. Journal of Clinical Investigation, 2010; 120 (1): 90-92 DOI: 10.1172/JCI41738
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