Abstract 547: Toll-Like Receptor 4 Signaling induces Systolic Blood Pressure Increase with Age
Background: Systolic blood pressure (SBP) increases steadily with age in industrialized Western societies and bears an independent continuous relationship with the incidence of cardiovascular events. The molecular mechanisms linking age and SBP remain uncertain, but vascular aging is one suspected pathomechanism.
Vascular aging is characterized by increased aortic stiffness and promoted by oxidative stress. The origin of oxidative stress is multifactorial, but Toll-like receptor 4 (TLR4) as regulator of innate immunity is an important inducer. We hypothesized that TLR4 mediates oxidative burden during physiological aging, promotes vascular stiffness and increased systolic blood pressure.
Methods: We investigated adult (6-9 months) and aged (12-15 months) C57Bl/6j and TLR4 null-mice (n=12/group). We determined blood pressure using tail-cuff plethysmography. Oxidative burden was determined by MDA. Vascular stiffness was assessed by aortic pulse wave velocity using the Complior and determination of aortic distensibility and compliance using ultrasound technique.
Results: Here we show that the SBP increase with age (6±2mmHg) is abolished in aged TLR4 null-mice as compared to C57Bl/6j mice. With respect to vascular aging we show that despite similar aPWV in adult mice (2.2±0.2m/s) in aged TLR4 null-mice aortic stiffness is ameliorated (2.5±0.7m/s) as compared to C57Bl/6j mice (4.2±0.7m/s) and oxidative damage as determined by MDA was abolished in TLR4 null mice. Aortic distensibility reduced in both strains during aging. Aortic compliance was reduced with age only in C57Bl/6j mice, not TLR4 null mice.
Conclusion: We suggest that the lack of TLR4 signaling reduced the aging associated cumulative oxidative burden. This ameliorated the development of aortic stiffness with age. The ameliorated vascular aging in TLR4 null-mice protected against the SBP increase with age.
Author Disclosures: M. Baumann: None. S. Kemmner: None. S. Chmielewski: None. C. Aoqui: None. U. Heemann: None.
- © 2014 by American Heart Association, Inc.