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Human Skeletal Muscle Feed Artery Function: Role of the Advanced Glycation End‐Products Receptor (RAGE)
Author(s) -
Park Soung Hun,
Kwon Oh Sung,
Andtbacka Robert H. I.,
Hyngstrom John R.,
Richardson Russell S.
Publication year - 2017
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.31.1_supplement.684.14
Subject(s) - vasodilation , rage (emotion) , medicine , electrical impedance myography , endocrinology , endothelium , endothelial dysfunction , sodium nitroprusside , nitric oxide , biology , neuroscience
Background Aging is associated with impaired endothelium‐dependent dilation in human skeletal muscle feed arteries (SMFAs), vessels recognized to have regulatory function. Although growing evidence implicates RAGE in inflammation and endothelial dysfunction, the role of RAGE in human vascular function and blood flow regulation with advancing age is not well understood. Therefore, this study investigated the relative abundance of RAGE in the SMFAs from young and old humans and the relationship between RAGE abundance and SMFA vasodilatory function. Methods RAGE protein expression was assessed in both young (28±4 yrs, n=6) and old (75±7 yrs, n=6) subjects with Western blot analysis. Endothelium‐dependent vasodilatory function was assessed in SMFAs, using pressure myography, in response to flow‐induced shear stress and acetylcholine (ACh). Endothelium‐independent vasodilatory function was assessed, in response to sodium nitroprusside (SNP). Results An age‐related attenuation in endothelial‐dependent vasodilatory function was evident in response to flow (Young: 98 ± 15; Old: 30 ± 17%, P < 0.05) and ACh (Young: 98±10; Old: 61±13 %, P < 0.05), while the endothelial‐independent response to SNP was not affected by age. SMFA RAGE expression increased with age ( p <0.05) and there was a significant negative correlation between RAGE protein expression and both flow (r 2 = −0.8783, P < 0.05) and ACh (r 2 = −0.7824, P < 0.05) induced vasodilation. There was no such relationship for RAGE and SNP induced vasodilation. Conclusions These findings imply that RAGE may play a critical role in the age‐related endothelial dysfunction documented in human SMFAs. Furthermore, this RAGE linked endothelial dysfunction may limit skeletal muscle blood flow and contribute to cardiovascular disease in the elderly. Support or Funding Information NIH Heart, Lung, Blood Institute grants (HL‐ 091830) and Veterans Affairs Rehabilitation Research and Development Merit (E6910‐R)