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Toll‐like receptor 9 contributes to increased vascular tone via small GTPase activation
Author(s) -
McCarthy Cameron G.,
Wenceslau Camilla F.,
Ogbi Safia,
Szasz Theodora,
Webb R. Clinton
Publication year - 2016
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.30.1_supplement.942.11
Subject(s) - rhoa , tlr9 , gtpase , receptor , medicine , endocrinology , cdc42 , actin cytoskeleton , microbiology and biotechnology , signal transduction , biology , chemistry , cytoskeleton , cell , biochemistry , gene expression , gene , dna methylation
Toll‐like receptor (TLR)9 is a pattern recognition receptor of the innate immune system. We have previously reported that TLR9 stimulation causes resistance artery dysfunction via increased sensitivity to norepinephrine, and this contributed to the pathogenesis of hypertension. However, the mechanisms underlying this increased vascular tone after TLR9 activation need to be further clarified. We hypothesized that TLR9 activation would increase expression of small GTPases, indicative of actin cytoskeleton remodeling. Isolated mesenteric resistance arteries from Sprague‐Dawley rats (n=4–6) were divided into three sections for Western blot analysis of Rho family small GTPases. Each section was incubated for 20 minutes in Krebs solution with either vehicle (endotoxin free water), TLR9 agonist ODN2395 (2 μM), or ODN2395 after a 5‐minute pre‐incubation with TLR9 antagonist ODN2088 (20 μM). ODN2395 alone increased protein expression of cdc42 (1.7 fold vs. Veh, p<0.05) and RhoA (1.4 fold vs. Veh, p<0.05), and this increase in expression was inhibited by pre‐incubation with ODN2088 (p>0.05). On the other hand, Rac1 was unchanged after incubation with ODN2395 (p>0.05). These results show that TLR9 stimulation leads to activation of some Rho family small GTPases and suggests another mechanism by which TLR9 causes increased vascular tone is actin cytoskeleton remodeling. Support or Funding Information American Heart Association (AHA) and National Institutes of Health (NIH)