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1.7 TLR4 Signaling Mediates SBP Increase with Age—a Translational Investigation

Abstract

Background

Systolic blood pressure (SBP) increases steadily with age. More than 50% of people aged 60+ are hypertensive. One suspected pathomechanism of SBP increase with age is aortic stiffness reflecting vascular aging. Oxidative stress contributes to aortic stiffness. An important regulator of oxidative stress is Toll-like receptor 4 (TLR4). We hypothesized that lifelong TLR4 mediated oxidative stress increases aortic stiffness and contributes to SBP increase with age.

Methods

We investigated adult (3–6 months of age) aged (9–12 months of age) and advance aged (15–18 months of age) male C57Bl/6j and TLR4 null-mice mice. We assessed SBP, aortic stiffness (aortic pulse wave velocity, aPWV) and aortic oxidative burden with malondialdehyde (MDA) in aging. In a translational study we analyzed in a cohort of 2679 patients with myocardial infarction the effect of TLR4 896A/G single nucleotide polymorphism on SBP, pulse pressure and hypertension in dependency on age.

Results

C57Bl/6j and TLR4 null-mice had in adulthood similar SBP, aPWV and similar oxidative burden. During aging in C57Bl/6j mice SBP, aPWV and MDA increased (15mmHg, 2m/s, 30%, respectively). Aged TLR4 null-mice did not show these changes. In the upper age tertile of the patient cohort (age >70 years), patients with a TLR4 896A/G single nucleotide polymorphism had lower SBP and pulse pressure (7mmHg) and less hypertension (79% versus 60%). The TLR4 SNP remained a significant predictor for SBP in univariate and multivariate regression analysis.

Discussion

We propose that TLR4 signaling participates in SBP increase with age by inducing vascular aging.

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This is an open access article distributed under the CC BY-NC license http://creativecommons.org/licenses/by/4.0/.

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Baumann, M., Schneider, S., Kemmner, S. et al. 1.7 TLR4 Signaling Mediates SBP Increase with Age—a Translational Investigation. Artery Res 8, 123 (2014). https://doi.org/10.1016/j.artres.2014.09.056

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  • DOI: https://doi.org/10.1016/j.artres.2014.09.056