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Lower soluble RAGE and higher aortic stiffness in African American adolescents: possible protective effect of higher sRAGE in white youth (867.10)
Author(s) -
Tank Ericka,
WegmanPoints Lauren,
Siefers Kyle,
Guinter Mark,
Pajaniappan Mohana,
Darracott Katherine,
Pierce Gary
Publication year - 2014
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.28.1_supplement.867.10
Subject(s) - glycation , rage (emotion) , medicine , pulse wave velocity , receptor , arterial stiffness , endocrinology , matrix metalloproteinase , elastin , mmp9 , mmp1 , blood pressure , cardiology , chemistry , pathology , downregulation and upregulation , gene expression , biochemistry , biology , neuroscience , gene
Advanced glycation end‐products (AGEs) are associated with increased aortic stiffness and cardiovascular disease (CVD) risk in middle‐aged/older adults. AGEs increase cross‐linking of extracellular matrix (ECM) proteins and binding to the Receptor for AGE (RAGE) activates vascular pro‐inflammatory/oxidant signaling. Matrix metalloproteinases (MMPs) degrade vascular ECM proteins such as elastin and cleave cell surface receptors such as RAGE. The cleaved soluble isoform of RAGE (sRAGE) serves as a ‘sink’ for circulating AGEs, so that low sRAGE is associated with increased CVD risk and high sRAGE may be vascular protective. Interestingly, sRAGE is lower in African‐American (AA) compared with white middle‐aged/older adults and is hypothesized to contribute in part to higher CVD risk in AAs. However, it is unknown if lower sRAGE is present in AA youth and associated with increased aortic stiffness. Circulating sRAGE was significantly lower in AA (n=20, age 16.8±1.4 yrs; BMI 24±3 kg/m 2 ) compared with white (n=24; age 16.5±1.5 yrs; BMI 23±4 kg/m 2 ) healthy adolescents (930 ± 432 vs. 1567 ±338 pg/ml, P<0.01), in the absence of differences in blood pressure (BP), AGEs, MMP9 and MMP2 (P>0.05). Aortic stiffness (carotid‐femoral artery pulse wave velocity, CFPWV) was higher in AA compared with whites (5.9±0.9 vs. 5.3±0.8 m/sec, P<0.05). After adjusting for age, BMI and mean BP, sRAGE was negatively correlated with CFPWV only in females (r=‐0.60, P<0.01) mostly from the relation among white (r=‐0.86, P<0.01) and not AA (r=‐0.51, P=0.16) females. In males, MMP2 was positively correlated with CFPWV (r=0.53, P<0.05) and sRAGE (r=‐0.54, P<0.05). Young AAs demonstrate lower circulating sRAGE and higher aortic stiffness compared with their white age‐ and BMI‐ matched peers. Whether lower sRAGE contributes to aortic stiffness in AAs or higher sRAGE has a vascular protective effect on large elastic arteries in whites deserves further investigation. Grant Funding Source : Supported by APS Undergraduate Research Fellowship; Univ of Iowa ICRU Fellowship; GHSU CHDI