CD44 Regulates Vascular Gene Expression in a Proatherogenic Environment

Objective— To identify early changes in vascular gene expression mediated by CD44 that promote atherosclerotic disease in apolipoprotein E (apoE)–deficient (apoE−/−) mice. Methods and Results— We demonstrate that CD44 is upregulated and functionally activated in aortic arch in the atherogenic environment of apoE−/− mice relative to wild-type (C57BL/6) controls. Moreover, CD44 activation even in apoE−/− mice is selective to lesion-prone regions because neither the thoracic aorta from apoE−/− mice nor the aortic arch of C57BL/6 mice exhibited upregulation of CD44 compared with thoracic aorta of CD57BL/6 mice. Consistent with these observations, gene expression profiling using cDNA microarrays and quantitative polymerase chain reaction revealed that ≈155 of 19 200 genes analyzed were differentially regulated in the aortic arch, but not in the thoracic aorta, in apoE−/− CD44−/− mice compared with apoE−/− CD44+/+ mice. However, these genes were not regulated by CD44 in the context of a C57BL/6 background, illu...