Reduced large elastic artery stiffness with regular aerobic exercise in middle-aged and older adults

Abstract

Objective Aortic pulse-wave velocity (aPWV) increases with age and is a strong independent predictor of incident cardiovascular diseases (CVDs) in healthy middle-aged and older adults. aPWV is lower in middle-aged and older adults who perform regular aerobic exercise than in their sedentary peers. As exercise is associated with reduced systemic inflammation, we hypothesized that suppression of the pro-inflammatory transcription factor nuclear factor κ B (NFκB) may mediate this process. Methods aPWV was measured in young sedentary [n =10, blood pressure (BP) 108 ± 3/59 ± 2 mmHg; mean ± SEM], middle-aged and older sedentary (n =9, 124 ± 7/73 ± 5 mmHg) and middle-aged and older aerobic exercise-trained (n =12, 110 ± 4/67 ± 2 mmHg) healthy, nonhypertensive men and women. Results Baseline aPWV increased with age [626 ± 14 (young sedentary) vs. 859 ± 49 (middle-aged and older sedentary) cm/s, P <0.001] but was 20% lower in middle-aged and older trained (686 ± 30 cm/s) than in middle-aged and older sedentary (P <0.005). Short-term (4 days × 2500–4500 mg) treatment with the NFκB inhibitor salsalate (randomized, placebo-controlled cross-over design) reduced aPWV (to 783 ± 44 cm/s, P <0.05) without changing BP (P =0.40) or heart rate (P =0.90) in middle-aged and older sedentary, but had no effect in young sedentary (623 ± 19) or middle-aged and older trained (699 ± 30). Following salsalate treatment, aPWV no longer was significantly different in middle-aged and older sedentary vs. middle-aged and older trained (P =0.29). The reduction in aPWV with salsalate administration was inversely related to baseline (placebo) aPWV (r = −0.60, P <0.001). Conclusion These results support the hypothesis that suppressed NFκB signalling may partially mediate the lower aortic stiffness in middle-aged and older adults who regularly perform aerobic exercise. Because aPWV predicts incident cardiovascular events in this population, this suggests that tonic suppression of NFκB signalling in middle-aged and older exercising adults may potentially lower cardiovascular risk.

IL-1 Inhibition and Vascular Function in CKD

“…12,44,49 aPWV was measured as described in detail previously. 12,50,51 Briefly, a transcutaneous custom tonometer (University of Colorado used a Noninvasive Hemodynamics Workstation; Cardiovascular Engineering Inc., Norwood, MA; and Vanderbilt University used a Sphygmocor; AtCor Medical, Itasca, IL) was positioned at the carotid, brachial, radial, and femoral arteries to noninvasively assess aPWV and carotid-radial pulse-wave velocity (an index of peripheral stiffness [Denver site only]). Distance between the suprasternal notch and femoral artery was measured using a custom raised ruler (Noninvasive Hemodynamics Workstation) or tape measure (all other distances).…”

Inflammation as a mediator of arterial ageing

“…In smaller mechanistic studies, short-term inhibition of NF B with salsalate improved EDD in older adults (Figure 2 (Pierce et al, 2009). In a subsequent investigation, the same shortterm inhibition of NF B improved PWV in older adults (Jablonski et al, 2015). Supporting this line of evidence, inflammation induced via vaccination acutely impairs EDD in young, healthy subjects (Hingorani et al, 2000).…”

“…Interestingly, in this cohort, salsalate reduced endothelial cell NFκB, oxidative stress and ROS‐producing enzymes, but not endothelial cell or systemic cytokines/chemokines (Pierce et al., ). In a subsequent investigation, the same short‐term inhibition of NFκB improved PWV in older adults (Jablonski et al., ). Supporting this line of evidence, inflammation induced via vaccination acutely impairs EDD in young, healthy subjects (Hingorani et al., ).…”

“…Habitually exercising older adults exhibit lower PWV compared with their sedentary counterparts, and improvements in PWV induced by inhibition of NFκB occur only in sedentary older adults (Jablonski et al., ), suggesting that NFκB activity is restrained by chronic exercise. Habitually exercising older adults also exhibit blunted endothelial senescence and production of SASP components compared with their sedentary counterparts (Rossman et al., ).…”

Intrauterine growth restriction influences vascular remodeling and stiffening in the weanling rat more than sex or diet

“…IUGR increases MMP-9 and TIMP-2, critical players in increased collagen content and vascular stiffening with aging and may be important modulators in IUGR-induced vascular stiffening through mechanisms such as oxidative stress (20,22). Oxidative stress activates vascular inflammation along with increased AGEs and nuclear factor-B (NF-B) contributing to the arterial stiffening pathway in aging (21,30). However, in our model AGEs decreased with IUGR and IUGR ϩ HFD possibly in part due to increased insulin sensitivity and decreased exposure to post-prandial glucoses thus decreasing the protein glycation after exposure to circulating sugars.…”