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Shear stress reversal amplifies arteriogenesis in the mouse ischemic hindlimb model and augments a pro‐arteriogenic ICAM‐1 hi /KLF2 hi endothelial phenotype
Author(s) -
Heuslein Joshua L,
Meisner Joshua K,
Blackman Brett R,
Price Richard J
Publication year - 2013
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.27.1_supplement.527.2
Subject(s) - arteriogenesis , klf2 , enos , endothelium , regulator , microbiology and biotechnology , mechanotransduction , chemistry , medicine , biology , nitric oxide , downregulation and upregulation , ischemia , nitric oxide synthase , biochemistry , gene
Femoral artery occlusion in the mouse leads to increased flow across all collateral arteries with some collateral segments also experiencing a reversal of flow direction. We have recently shown that these “flow reversal” segments exhibit an amplified arteriogenesis response (i.e. 22% and 33% diameter increases in “flow reversed” over “non‐reversed” segments by days 3 and 7, respectively) and a 4‐fold increase in pericollateral CD45 + cells (day 3). Thus, we hypothesize that these “flow reversed” collateral segments could provide clues for how to amplify arteriogenesis therapeutically. To this end, we studied the expression of markers of a pro‐arteriogenic endothelial phenotype in response to an in vitro shear stress protocol mimicking the in vivo hemodynamics. We observed rapid endothelial cell repolarization and 30% increases in KLF2 (regulator of pro‐arteriogenic eNOS), eNOS, and ICAM‐1 (pro‐arteriogenic regulator of monocyte adhesion) mRNA expression in reversed conditions compared to non‐reversed. These results are consistent with the hypothesis that, when coupled with increased shear stress magnitude, the reversal of shear stress direction leads to enhanced arteriogenesis by activating KLF2 and ICAM‐1. Sources of research support: NIH HL098632 and AHA10GRNT3490001.