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CC Chemokine Receptor 5 Directs Macrophage Function Following Myocardial Infarction
Author(s) -
Zamilpa Rogelio,
Kanakia Rushit,
Cigarroa Joaquin,
Martinez Hernan,
Jimenez Fabio,
Ahuja Seema S.,
Lindsey Merry L.
Publication year - 2010
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.24.1_supplement.1029.10
Subject(s) - chemokine , medicine , ventricular remodeling , chemokine receptor , matrix metalloproteinase , macrophage , ventricle , endocrinology , myocardial infarction , receptor , cc chemokine receptors , ccl3 , inflammation , chemistry , immunology , ccl2 , in vitro , biochemistry
The CC Chemokine Receptor 5 (CCR5) is a key chemokine receptor expressed on macrophages, and CCR5 ligands are highly upregulated post‐MI. However, the role of CCR5 in post‐MI remodeling of the left ventricle (LV) has not been investigated. Accordingly, we examined LV function, plasma inflammatory markers, macrophage infiltration, matrix metalloproteinase‐9 (MMP‐9), and collagen content in wild‐type mice (WT, n=25) and CCR5 null mice (Null, n=33) at 7 days post‐MI. While MI sizes were similar between the groups (44±2% in WT and 42±2% in Null), the LV remodeling index was higher in the CCR5 null mice. The higher LV remodeling index was associated with attenuated plasma IL‐6, IFN‐γ and TNFα levels and lower LV macrophage numbers (7±1% of total infarct area compared to 11±1% in WT; p<0.05). In addition, the concomitant increases of MMP‐9 and crosslinked collagen in LV infarcts were not observed in the CCR5 null mice. These results indicated that CCR5 deletion imparted a net negative effect post‐MI by decreasing macrophage numbers to impair the inflammatory response, reduce collagen content, and increase the remodeling index. NIH (R01 HL‐75360), AHA (0855119F) to M.L.L., AHA (09POST2150178) to R.Z and VA Merit to S.S.A.