Arterial stiffening, wave reflection, and inflammation in habitually exercising systemic lupus erythematosus patients.

BACKGROUND: Chronic systemic inflammation has been implicated in the pathogenesis of hypertension and cardiovascular disease. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation and an increased risk for cardiovascular disease. Currently few studies have evaluated the potential cardiovascular benefits of exercise in SLE. It is unknown whether the favorable effect of habitual exercise on arterial stiffness observed in healthy adults can be extended to SLE. Therefore, as an initial step, we determined the association between habitual exercise, inflammatory markers, central arterial compliance, and aortic wave reflection in healthy adults and SLE patients. METHODS: We studied 41 adults, aged 33 ± 11 years (15 healthy controls, 12 sedentary SLE, and 14 physically active SLE patients). RESULTS: Age, body mass index, and metabolic risk factors were not different between the three groups. Carotid arterial compliance was lower whereas augmentation index (AI) and inflammatory markers (C-reactive protein (CRP), interleukin (IL)-12, tumor necrosis factor-α (TNF-α)) were higher in sedentary SLE patients compared with healthy controls, but were not different between physically active SLE patients and healthy controls. Cardiac ejection fraction was lower in sedentary SLE than physically active SLE or healthy controls. In the pooled population, carotid arterial compliance was inversely associated with TNF-α (r = -0.38; P < 0.01), and AI was positively associated with both CRP (r = 0.33; P < 0.05) and intercellular adhesion molecule-1 (r = 0.28; P < 0.05). CONCLUSIONS: SLE-associated stiffening of the central artery and wave reflection were not observed in habitually exercising adults with SLE. Furthermore, greater arterial stiffness was associated with higher inflammatory markers, suggesting that need for studies on inflammation and SLE-associated arterial stiffening.

Habitual resistance exercise and endothelial ischemia-reperfusion injury in young adults.

Resistance exercise involves muscular contractions that can render downstream tissues ischemic and may precondition the vasculature against ischemia-reperfusion (IR) injury, but it is unknown if habitual resistance exercise protects against IR injury in humans. We determined the magnitude and recovery from endothelial IR injury induced by forearm occlusion in 22 healthy young sedentary and resistance-trained adults. After IR injury, brachial artery flow-mediated dilation (FMD) significantly decreased by 36% in sedentary, but not resistance-trained subjects and fully recovered within 45 min. Though HDL-cholesterol, handgrip strength and systolic blood pressure were significantly associated with FMD 15 min after IR injury, the change in FMD from before to 15 min after IR injury was not associated with any subject characteristics. These results are consistent with the notion that habitual resistance exercise may protect against endothelial IR injury in young adults, presumably through effects analogous to ischemic preconditioning.

Use of temperature alterations to characterize vascular reactivity.

Monitoring alterations in fingertip temperature during ischaemia and the subsequent hyperaemia provides a novel way of studying microvascular reactivity. The relations between parameters characterizing blood perfusion and the thermal response of fingertips were studied using experimental and theoretical approaches. During the experimental protocol, two brachial artery occlusion tests were conducted in 12 healthy volunteers, and fingertip temperature, heat flux and skin perfusion using laser Doppler flowmetry (LDF) were measured. The temperature curves provide a smooth and robust response that is able to capture occlusion and reperfusion. The temperature fall during occlusion as well as the maximum temperature recorded depended linearly on the initial temperature. The magnitude of the LDF signal was associated with local tissue temperature and followed an exponential response. Heat flux measurements demonstrated rapid changes and followed variations in blood perfusion closely. The time points at which the heat flux reached its maximum corresponded to the time at which the fingertip temperature curves showed an inflection point after cuff release. The time required for the fingertip temperature to arrive at the maximum temperature was greater than the time to peak for the heat flux signal, which was greater than the LDF signal to reach a maximum. The time lag between these signals was a function of the finger size and finger temperature at the moment reperfusion restarted. Our present results indicate that finger temperature, heat flux and perfusion display varying rates of recovery following ischaemic stimuli and that differential responses are associated with the initial finger temperature.

Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity.

The clinical importance of vascular reactivity as an early marker of atherosclerosis has been well established, and a number of established and emerging techniques have been employed to provide measurements of peripheral vascular reactivity. However, relations between these methodologies are unclear as each technique evaluates different physiological aspects related to micro- and macrovascular reactive hyperemia. To address this question, a total of 40 apparently healthy normotensive adults, 19-68 yr old, underwent 5 min of forearm suprasystolic cuff-induced ischemia followed by postischemic measurements. Measurements of vascular reactivity included 1) flow-mediated dilatation (FMD), 2) changes in pulse wave velocity between the brachial and radial artery (DeltaPWV), 3) hyperemic shear stress, 4) reactive hyperemic flow, 5) reactive hyperemia index (RHI) assessed by fingertip arterial tonometry, 6) fingertip temperature rebound (TR), and 7) skin reactive hyperemia. FMD was significantly and positively associated with RHI (r=0.47) and TR (r=0.45) (both P<0.01) but not with reactive hyperemic flow or hyperemic shear stress. There was no correlation between two measures of macrovascular reactivity (FMD and DeltaPWV). Skin reactive hyperemia was significantly associated with RHI (r=0.55) and reactive hyperemic flow (r=0.35) (both P<0.05). There was a significant association between reactive hyperemia and RHI (r=0.30; P<0.05). In more than 75% of cases, vascular reactivity measures were not significantly associated. We concluded that associations among different measures of peripheral micro- and macrovascular reactivity were modest at best. These results suggest that different physiological mechanisms may be involved in changing different measures of vascular reactivity.

Analysis of the roles of FlgP and FlgQ in flagellar motility of Campylobacter jejuni.

Flagellar motility is an important determinant of Campylobacter jejuni that is required for promoting interactions with various hosts to promote gastroenteritis in humans or commensal colonization of many animals. In a previous study, we identified a nonmotile mutant of C. jejuni 81-176 with a transposon insertion in Cj1026c, but verification of the role of the encoded protein in motility was not determined. In this study, we have determined that Cj1026c and the gene immediately downstream, Cj1025c (here annotated as flgP and flgQ, respectively), are both required for motility of C. jejuni but not for flagellar biosynthesis. FlgP and FlgQ are not components of the transcriptional regulatory cascades to activate sigma(28)- or sigma(54)-dependent expression of flagellar genes. In addition, expression of flgP and flgQ is not largely dependent on sigma(28) or sigma(54). Immunblot analyses revealed that the majority of FlgP in C. jejuni is associated with the outer membrane. However, in the absence of FlgQ, the amounts of FlgP in the outer membrane of C. jejuni are greatly reduced, suggesting that FlgQ may be required for localization or stability of FlgP at this location. This study provides insight into features of FlgP and FlgQ, two proteins with previously undefined functions that are required for the larger, multicomponent flagellar system of C. jejuni that is necessary for motility.