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Carotid intima‐media thickening is induced by low flow: roles for IL‐18 and Mif
Author(s) -
Korshunov Vyacheslav A,
Nikonenko Tatiana A,
Tkachuk Vsevolod A,
Brooks Andrew,
Berk Bradford C
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a198-c
Subject(s) - inflammation , immunohistochemistry , pathology , flow cytometry , medicine , thickening , biology , immunology , chemistry , polymer science
Carotid intima‐media thickening (IMT) is a form of vascular remodeling that has a strong genetic component. Recently, we discovered that SJL mice respond to decreased carotid blood flow by IMT that was 30‐fold greater than C3H mice. Thus, we hypothesized that IMT in SJL mice is associated with inflammation. We compared vascular remodeling among 2 “small” IMT (C3H/HeJ and C3HeB/FeJ) and 2 “big” IMT (FVB/NJ and SJL/J) inbred strains of mice. Quantitative immunohistochemistry showed a dramatic increase in inflammatory cells measured by CD45 (~130‐fold) and in the SJL compared to other strains. Microarray profiling of inflammatory gene mRNAs from carotids showed significant 2‐fold increases in IL‐18 and Mif gene expression in SJL compared to C3HeB/FeJ. Increased expression of these genes was confirmed by both quantitative RT‐PCR and immunohistochemistry. Furthermore, greater cell proliferation in the intima of SJL accounted for increased IMT, while a higher level of apoptosis and a lower level of proliferation were observed in C3HeB/FeJ. The present study indicates that increased expression of Mif and IL‐18 cytokines is associated with IMT in SJL mice, likely by stimulating inflammation and proliferation. Supported by NIH grant HL‐62836 to BCB.