PO-07 RACIAL DIFFERENCES IN CIRCULATING csRAGE AND ALTERNATIVELY SPLICED esRAGE IN HEALTHY ADOLESCENTS: RELATION WITH AORTIC STIFFNESS

Ericka Tank; Lauren Wegman-Points; Mohana Pajaniappan; Katherine Darracott; Gary L. Pierce

doi:10.1016/j.artres.2014.09.013

<Previous Article In Issue

Download article (PDF)

Next Article In Issue>

Volume 8, Issue 4, December 2014, Pages 168 - 169

PO-07 RACIAL DIFFERENCES IN CIRCULATING csRAGE AND ALTERNATIVELY SPLICED esRAGE IN HEALTHY ADOLESCENTS: RELATION WITH AORTIC STIFFNESS

Authors

Ericka Tank^a, Lauren Wegman-Points^a, Mohana Pajaniappan^c, Katherine Darracott^c, Gary L. Pierce^a^{, b}

^aDepartment of Health and Human Physiology, University of Iowa, Iowa City, IA, USA

^bFraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA

^cGeorgia Prevention Institute, Department of Pediatrics, Georgia Health Science University, Augusta, GA, USA

Available Online 4 November 2014.

DOI: 10.1016/j.artres.2014.09.013 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC license.

Background: Binding of ligands to the receptor for advanced glycation end products (RAGE) triggers pro-inflammatory/oxidant signaling in the vascular wall. Increased circulating soluble forms of RAGE (sRAGE) are associated with decreased vascular risk and may be protective by acting as a decoy to prevent ligand binding to full-length RAGE. Sheddases, such as matrix metalloproteinase-9 (MMP 9) proteolytically cleave cell surface receptors including RAGE, forming cleaved soluble RAGE (csRAGE). However, sRAGE also includes endogenous secretory RAGE (esRAGE), an isoform of RAGE without receptor function derived from alternative splicing of RAGE pre-mRNA. sRAGE is lower in African-American (AA) compared with Caucasian adults and is hypothesized to contribute to elevated arterial stiffening and vascular risk in AAs. Indeed, we have previously demonstrated that sRAGE (1567±68.9 vs. 955±101.1 pg/mL, p<0.001) but not MMP9 is higher in Caucasian compared with AA adolescents and associated with lower carotid-femoral pulse wave velocity (CFPWV) (5.3±0.2 vs. 5.9±0.2 m/sec, p<0.05).

Objectives: We hypothesized that increased sRAGE in Caucasian versus AA adolescents is from increased circulating esRAGE through alternative splicing of RAGE pre-mRNA.

Methods and results: Circulating esRAGE (ELISA) was significantly higher (369±24.8 vs. 242±26.5 pg/mL, P<0.01) in Caucasian (n=24, age 16.5±0.3 yrs; BMI 22.9±0.8 kg/m²) vs. AA (n=15, age 16.8±0.3 yrs; BMI 24.5±1.0 kg/m²) adolescents (P>0.05). esRAGE was correlated with sRAGE (r=0.708, P<0.001), but esRAGE:sRAGE ratio did not differ between race (0.24±0.01 vs. 0.33±0.09, p>0.05). Preliminary data in pooled Caucasian (n=3) human umbilical vein endothelial cells (HUVECs) demonstrates greater esRAGE mRNA (qRT-PCR) than AA HUVECs, but similar full-length RAGE mRNA.

Conclusion: These preliminary data suggest that higher sRAGE in Caucasian compared with AA adolescents is likely not from higher esRAGE but a combination of cleavage from non-MMP9 sheddases and alternative splicing of RAGE.

<Previous Article In Issue

Download article (PDF)

Next Article In Issue>

Journal: Artery Research
Volume-Issue: 8 - 4
Pages: 168 - 169
Publication Date: 2014/11/04
ISSN (Online): 1876-4401
ISSN (Print): 1872-9312
DOI: 10.1016/j.artres.2014.09.013 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC license.

Cite this article

ris enw bib

TY  - JOUR
AU  - Ericka Tank
AU  - Lauren Wegman-Points
AU  - Mohana Pajaniappan
AU  - Katherine Darracott
AU  - Gary L. Pierce
PY  - 2014
DA  - 2014/11/04
TI  - PO-07 RACIAL DIFFERENCES IN CIRCULATING csRAGE AND ALTERNATIVELY SPLICED esRAGE IN HEALTHY ADOLESCENTS: RELATION WITH AORTIC STIFFNESS
JO  - Artery Research
SP  - 168
EP  - 169
VL  - 8
IS  - 4
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2014.09.013
DO  - 10.1016/j.artres.2014.09.013
ID  - Tank2014
ER  -

download .riscopy to clipboard