TY - JOUR
T1 - Double-stranded RNA and Toll-like receptor activation
T2 - A novel mechanism for blood pressure regulation
AU - Dela Justina, Vanessa
AU - Giachini, Fernanda R.
AU - Priviero, Fernanda
AU - Webb, R. Clinton
N1 - Funding Information:
This study was supported by National Institutes of Health (NIH) [grant number PO1 HL-13604 (to R.C.W.)]; Fundac¸ ão de Amparo à Pesquisa do Estado de Mato Grosso (FAPEMAT) [grant number 0324552/2018 (to F.R.G.)]; Conselho Nacional de Desenvolvi-mento Científico e Tecnológico (CNPq) [grant number 305823/2015-9 (to F.R.G.)]; and Coordenac¸ ão de Aperfeic¸ oamento de Pes-soal de Nível Superior (CAPES) [grant number 88881.190484/2018-01 Scholarship (to V.D.J.)].
Publisher Copyright:
© 2020 The Author(s).
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Toll-like receptors (TLRs), such as TLR4 and 9, recognize pathogen-associated molecular pattern (PAMPs) and danger-associated molecular patterns (DAMPs) and are associated with increased blood pressure (BP). TLR3, residing in the endosomal compartment, is activated by viral double-stranded RNA (dsRNA) leading to activation of TIR receptor domain-containing adaptor inducing IFN-β (TRIF) dependent pathway. Besides foreign pathogens, the immune system responds to endogenous markers of cellular damage such as mitochondrial dsRNA (mtdsRNA). New evidence has shown a link between dsRNA and increased BP. Moreover, TLR3 activation during pregnancy was demonstrated to develop preeclampsia-like symptoms in both rats and mice. Hence, we hypothesize that the dsRNA derived from viral nucleic acids or cellular damage (mtdsRNA) will increase the inflammatory state through activation of TLR3, contributing to vascular dysfunction and increased BP. Therefore, inhibition of TLR3 could be a therapeutic target for the treatment of hypertension with potential improvement in vascular reactivity and consequently, a decrease in BP.
AB - Toll-like receptors (TLRs), such as TLR4 and 9, recognize pathogen-associated molecular pattern (PAMPs) and danger-associated molecular patterns (DAMPs) and are associated with increased blood pressure (BP). TLR3, residing in the endosomal compartment, is activated by viral double-stranded RNA (dsRNA) leading to activation of TIR receptor domain-containing adaptor inducing IFN-β (TRIF) dependent pathway. Besides foreign pathogens, the immune system responds to endogenous markers of cellular damage such as mitochondrial dsRNA (mtdsRNA). New evidence has shown a link between dsRNA and increased BP. Moreover, TLR3 activation during pregnancy was demonstrated to develop preeclampsia-like symptoms in both rats and mice. Hence, we hypothesize that the dsRNA derived from viral nucleic acids or cellular damage (mtdsRNA) will increase the inflammatory state through activation of TLR3, contributing to vascular dysfunction and increased BP. Therefore, inhibition of TLR3 could be a therapeutic target for the treatment of hypertension with potential improvement in vascular reactivity and consequently, a decrease in BP.
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U2 - 10.1042/CS20190913
DO - 10.1042/CS20190913
M3 - Article
C2 - 31998948
AN - SCOPUS:85078689764
SN - 0143-5221
VL - 134
SP - 303
EP - 313
JO - Clinical Science
JF - Clinical Science
IS - 2
ER -