Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension.

Abstract:

AIMS:Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key component of the innate immune system, which is activated by exogenous and endogenous ligands. Hypertension is associated with end-organ damage and thus might lead to the release of damage-associated molecular patterns (DAMPs), which are endogenous activators of TLR4 receptors. The present study aimed to elucidate whether TLR4 signalling is able to modulate vascular contractility in an experimental model of hypertension thus contributing to blood pressure regulation. METHODS AND RESULTS:NG-nitro-l-arginine methyl ester (l-NAME)-induced hypertension was blunted in TLR4(-/-) when compared with wild-type mice. Treatment with l-NAME was associated with a release of DAMPs, leading to reactive oxygen species production of smooth muscle cells in a TLR4-dependent manner. As oxidative stress leads to an impaired function of the NO-sGC-cyclic GMP (cGMP) pathway, we were able to demonstrate that TLR4(-/-) was protected from sGC inactivation. Consequently, arterial contractility was reduced in TLR4(-/-). CONCLUSIONS:Cell damage-associated TLR4 signalling might act as a direct mediator of vascular contractility providing a molecular link between inflammation and hypertension.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Sollinger D,Eißler R,Lorenz S,Strand S,Chmielewski S,Aoqui C,Schmaderer C,Bluyssen H,Zicha J,Witzke O,Scherer E,Lutz J,Heemann U,Baumann M

doi

10.1093/cvr/cvt265

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

464-72

issue

3

eissn

0008-6363

issn

1755-3245

pii

cvt265

journal_volume

101

pub_type

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