Impact Of Acute Antioxidant Supplementation On Neural Cardiovascular Control In Psoriatic Subjects

Recent studies indicate psoriasis not only affects the skin and joints, but, as a systemic inflammatory disorder, is also associated with increased risk of vascular complications leading to myocardial infarction and stroke. Systemic inflammation is a contributor to heightened cardiovascular disease risk. Individuals with psoriasis have been shown to have altered cardiovascular regulation; however, the underlying mechanisms are unclear. Cellular oxidative stress, if not managed by antioxidants, can destabilize the cell and lead to cellular damage causing chronic inflammation. Heightened oxidative stress and inflammation can lead to heightened muscle sympathetic nerve activity and vascular dysfunction - most notably decreased nitric oxide bioavailability, along with hypertension, COPD, and heart failure. Oxidative stress and inflammation, like that seen in psoriasis, is suspected of causing impaired vascular function. These two factors may be causing exaggerated muscle sympathetic nerve activity, increases in blood pressure, vascular dysfunction, and decreased exercise tolerance. These factors can ultimately contribute to cardiovascular disease development in psoriatic subjects. Therefore, the purpose of this study is to examine vascular function and muscle sympathetic nerve activity at rest and during exercise, prior to and following an acute antioxidant supplementation designed to dampen systemic inflammation, oxidative stress, and MSNA in diagnosed subjects with psoriasis

Predictors of Performance during a 161 km Mountain Footrace

Training volume and cardiovascular dynamics influence endurance performance. However, there is limited information on the interplay between training volume, cardiovascular dynamics, and performance in ultra-marathon athletes. PURPOSE: We aimed to determine predictors of performance in finishers of the 2023 Western States Endurance Run (WSER). METHODS: Sixty participants who finished the race (49 males/11 females; mean age: 44.7 ± 9.6 y, range: 26–66 y; BMI: 22.7 ± 2.2 kg/m2) completed pre-race surveys including average training volume (AV) and peak training volume (PV), as well as resting cardiovascular measures including resting heart rate (RHR) and augmentation index (AIx), a measure of wave reflection characteristics. Based on WSER completion time, we calculated average running velocity (RV). We assessed associations among 22 variables using bivariate correlation analysis (Pearson’s Correlation for normally distributed data and Spearman’s Rank Correlation if normality was not met). Within our listed variables, normality was met in age and AV. Additionally, we completed multiple regression analyses for predictors. We present descriptive data as mean ± SD. RESULTS: Participants had an average RV of 6.33 ± 0.97 km/h (3.93 ± 0.6 mph), and reported an AV of 91.9 ± 24.5 km/wk (57.1 ± 15.2 miles/wk) and a PV of 141.0 ± 47.2 km/wk (87.6 ± 29.3 miles/wk). We observed significant associations between RV and age (r(58) = -0.57, p r(58) = 0.41, p r(58) = 0.34, p R2 = 0.37; F(3,56) = 12.4, pb1 = 0.013; t(56) = 2.57, p = 0.013), resulting in a 0.33 km/h increase in RV for every 25-km increase in AV. Last, significant relations existed between RV and AIx (r(58) = -0.30, p = 0.022); and RHR (r(58) = -0.26, p = 0.046). CONCLUSION: We found that (1) average weekly training volume is a significant predictor of performance in elite ultra-marathon athletes and (2) race performance was inversely associated with resting arterial wave reflection characteristics and heart rate

AGE AND PHYSICAL ACTIVITY DO NOT IMPACT CIRCULATING SOLUBLE CD14 CONCENTRATION IN APPARENTLY HEALTHY ADULTS

BACKGROUND: Soluble CD14 (sCD14) (cluster of differentiation 14) is a co-receptor of bacterial lipopolysaccharide that is released from monocytes upon activation. There is a well-recognized role of sCD14 in inflammation, and aging has been associated with increased inflammation and cardiometabolic health risk factors (e.g., high blood pressure [BP], hyperglycemia). However, there is limited information on the combined influence of aging and physical activity on circulating sCD14. Therefore, the purpose of this study was to examine the influence of aging on plasma sCD14 concentration and the potential influence of physical activity. METHODS: Twenty young (11 females, age 22.7± 2.6, body mass index 26.7 ± 3.3, BP 119/73 ± 7/8 mmHg) and 21 old (11 female, age 58.4 ± 7.4, body mass index 27.8 ± 4.8, BP 125/76 ± 12/8 mmHg) adults participated in the study. Physical activity (PA) was assessed using waist worn ActiGraph GT3X accelerometers for a minimum of 5-days (7.6 ± 1.6 days) to obtain average daily steps, sedentary time, and moderate and vigorous PA (MVPA). We measured brachial BP using a SpyghmoCor XCEL after 10-minutes of supine rest. We assessed plasma concentrations of sCD14 using an enzyme-linked immunosorbent assay kit. Normality was assessed using Shapiro-Wilk. Students’ T Test or Mann Whitney test were used to make age comparisons between young (\u3c35 years) and older (\u3e45 years) adults. Pearson’s correlation and Spearman’s rho, controlled for age, body mass index, and sex, were used to assess relations between MVPA and steps with sCD14. Statistical significance was set as p ≤ 0.05 RESULTS: There was not a difference between young and older adults in circulating sCD14 concentration (young: 2348 ± 441 vs. older: 2487 ± 541 pg/ml, p = 0.501). There was not a difference between young and older adults in MVPA (young: 47 ± 25 vs. older: 48 ± 24 min/day, p = 0.873) or average daily steps (young: 7179 ± 3171 vs. older: 7797 ± 3595 steps/day, p = 0.679). There were not associations between sCD14 and daily MVPA (r = -0.176, p = 0.343) or Steps (rho = -0.278, p = 0.130). CONCLUSION: Our preliminary data indicate that there were no age differences in circulating sCD14 and no associations between habitual physical activity and circulating sCD14

AGE AND PHYSICAL ACTIVITY DOES NOT IMPACT LIPOPOLYSACCHARIDE-BINDING PROTEIN CONCENTRATION IN APPARENTLY HEALTHY ADULTS

BACKGROUND: LBP (lipopolysaccharide‐binding protein) is an acute‐phase protein that binds lipopolysaccharide in the blood and plays a role in subsequent activation of immune cells through the production of proinflammatory cytokines. LBP is associated with future cardiovascular disease in middle-aged and older adults. However, there is limited information on the combined influence of aging and physical activity on circulating LBP. Therefore, the purpose of this study was to examine the influence of aging on plasma LBP concentration and the potential influence of physical activity. METHODS: Ten young (4 females, age 23.5 ± 2.2, body mass index 26.3 ± 2.5 blood pressure 120/74 ± 8/8 mmHg) and 11 old (4 female, age 60.7 ± 5.5, body mass index 27.2 ± 3.2, blood pressure 124/74 ± 12/6 mmHg) participated in the study. Physical activity (PA) was assessed using waist worn ActiGraph GT3X accelerometers for a minimum of 6-days (7.1 ± 0.5 days) to obtain average daily steps, sedentary time, and moderate and vigorous PA (MVPA). We measured brachial blood pressure using a SpyghmoCor XCEL after 10-minutes of supine rest. We assessed plasma concentrations of LBP using an enzyme-linked immunosorbent assay kit. Normality was assessed using Shapiro-Wilk. Students’ T Test or Mann Whitney test were used to make age comparisons between young (\u3c35 years) and older (\u3e45 years) adults. Pearson’s correlation, controlled for age, body mass index, and sex, was used to assess relations between MVPA and steps with LBP. Statistical significance was set as p ≤ 0.05 RESULTS: There was not a difference between young and older adults in circulating LBP concentration (young: 8045 ± 3222 vs. older: 8905 ± 7087 pg/ml, p = 0.605). There was not a difference between young and older adults in MVPA (young: 56 ± 30 vs. older: 51 ± 28 min/day, p = 0.748) or average daily steps (young: 8150 ± 4315 vs. older: 8358 ± 4158 steps/day, p = 0.921). There were not associations between LBP and daily MVPA (r = -0.188, p = 0.519) or Steps (r = -0.267, p = 0.356). CONCLUSION: Our preliminary data indicate that there were no age differences in circulating LBP and no associations between habitual physical activity and circulating LBP

AGING IS NOT ASSOCIATED WITH DECREASED KIDNEY VASCULAR CONDUCTANCE IN ULTRA-MARATHON RUNNERS

BACKGROUND: Vascular conductance refers to the ease with which blood flows through arteries. Vascular conductance is reduced with aging due to impairments of vascular structure (i.e., arterial stiffness and wall thickening) and function. Reduction in renal blood flow demonstrates an increase in blood pressure (BP) which contributes to the pathogenesis of hypertension. Habitual exercise reduces age-related declines in vascular function. Whether chronic ultra-endurance training offsets age-associated reductions in vascular conductance is largely unexplored. Therefore, we evaluated associations between age and kidney vascular conductance in ultra-marathon runners aged 22-66 years. METHODS: Thirty-nine ultra-marathon runners competing in the 2023 Western States 100-mile Endurance Run were included in this analysis (33 M/6 F, 41 ± 10 years, BMI: 23 ± 2 kg/m2; mean ± SD). Kidney blood velocity in the renal and segmental arteries was measured in the decubitus position using a GE Logiq e ultrasound (3 - 5 mHz). We measured supine brachial and central blood pressure using SphygmoCor XCEL. Renal and segmental artery conductance were calculated as blood velocity divided by central mean BP (cm●s-1/mmHg). All data were normally distributed (Shapiro-Wilk test, ps \u3e 0.05). We conducted Pearson’s r correlations between age and kidney vascular conductance and kidney blood velocity with α set at ≤ 0.05. RESULTS: Central mean BP in our sample was 92 ± 8 mmHg. Age was not associated with renal (0.58 ± 0.13 cm●s-1/mmHg; r = -0.243, p = 0.137) or segmental (0.35 ± 0.08 cm●s-1/mmHg; r = -0.239, p = 0.160) artery vascular conductance. Similarly, when central BP was not accounted for, age was not associated with renal (53 ± 12 cm●s-1; r = -0.086, p = 0.603) or segmental (32 ± 7 cm●s-1; r = -0.055, p = 0.748) artery velocity. CONCLUSIONS: While additional data in a larger sample size and age-matched control participants are needed, our data indicate that age is not associated with reduced resting kidney vascular conductance or blood velocity in ultra-marathon runners

Tracking peripheral vascular function for six months in young adults following SARS‐CoV‐2 infection

Abstract SARS‐CoV‐2 infection is known to instigate a range of physiologic perturbations, including vascular dysfunction. However, little work has concluded how long these effects may last, especially among young adults with mild symptoms. To determine potential recovery from acute vascular dysfunction in young adults (8 M/8F, 21 ± 1 yr, 23.5 ± 3.1 kg⋅m−2), we longitudinally tracked brachial artery flow‐mediated dilation (FMD) and reactive hyperemia (RH) in the arm and hyperemic response to passive limb movement (PLM) in the leg, with Doppler ultrasound, as well as circulating biomarkers of inflammation (interleukin‐6, C‐reactive protein), oxidative stress (thiobarbituric acid reactive substances, protein carbonyl), antioxidant capacity (superoxide dismutase), and nitric oxide bioavailability (nitrite) monthly for a 6‐month period post‐SARS‐CoV‐2 infection. FMD, as a marker of macrovascular function, improved from month 1 (3.06 ± 1.39%) to month 6 (6.60 ± 2.07%; p  0.05). Circulating markers of inflammation, oxidative stress, antioxidant capacity, and nitric oxide bioavailability did not change during the 6 months (p > 0.05). Together, these results suggest some improvements in macrovascular, but not microvascular function, over 6 months following SARS‐CoV‐2 infection. The data also suggest persistent ramifications for cardiovascular health among those recovering from mild illness and among young, otherwise healthy adults with SARS‐CoV‐2

Monthly transthoracic echocardiography in young adults for 6 months following SARS‐CoV‐2 infection

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can elicit acute and long‐term effects on the myocardium among survivors, yet effects among otherwise healthy young adults remains unclear. Young adults with mild symptoms of SARS‐CoV‐2 (8M/8F, age: 21 ± 1 years, BMI: 23.5 ± 3.1 kg·m−2) underwent monthly transthoracic echocardiography (TTE) and testing of circulating cardiac troponin‐I for months 1–6 (M1–M6) following a positive polymerase chain reaction test to better understand the acute effects and post‐acute sequelae of SARS‐CoV‐2 on cardiac structure and function. Left heart structure and ejection fraction were unaltered from M1–M6 (p > 0.05). While most parameters of septal and lateral wall velocities, mitral and tricuspid valve, and pulmonary vein (PV) were unaltered from M1–M6 (p > 0.05), lateral wall s′ wave velocity increased (M1: 0.113 ± 0.019 m·s−1, M6: 0.135 ± 0.022 m·s−1, p = 0.013); PV S wave velocity increased (M1: 0.596 ± 0.099 m·s−1, M6: 0.824 ± 0.118 m·s−1, p < 0.001); the difference between PV A wave and mitral valve (MV) A wave durations decreased (M1: 39.139 ± 43.715 ms, M6: 18.037 ± 7.227 ms, p = 0.002); the ratio of PV A duration to MV A duration increased (M1: 0.844 ± 0.205, M6: 1.013 ± 0.132, p = 0.013); and cardiac troponin‐I levels decreased (M1: 0.38 ± 0.20 ng·ml−1, M3: 0.28 ± 0.34 ng·ml−1, M6: 0.29 ± 0.16 ng·ml−1; p = 0.002) over time. While young adults with mild symptoms of SARS‐CoV‐2 lacked changes to cardiac structure, the subclinical improvements to cardiac function and reduced inflammatory marker of cardiac troponin‐I over 6 months following SARS‐CoV‐2 infection provide physiologic guidance to post‐acute sequelae and recovery from SARS‐CoV‐2 and its variants using conventional TTE

AGE-RELATED CARDIOVASCULAR HEALTH AMONG ELITE ULTRA-ENDURANCE ATHLETES

BACKGROUND: Aging is associated with increased cardiovascular (CV) disease risk which is partly attributable to increased blood pressure (BP) and central arterial stiffness. Regular exercise is recommended to slow CV aging, but it is unclear whether “extreme exercise”, such as ultra-endurance running (\u3e42.2 km), elicits the same CV benefits as lower-volume training. Therefore, the purpose of this investigation was to test the hypothesis that ultra-endurance running preserves CV health across the lifespan. METHODS: We measured supine BP with an automated brachial cuff and arterial stiffness (carotid-to-femoral pulse wave velocity [cfPWV]) with applanation tonometry (SphygmoCor XCEL, AtCor Medical) among 72 athletes (16F/56M; BMI: 22.6 ± 1.8 kg/m2) 1-3 days before they competed in the 161-km Western States Endurance Race (WSER) (Olympic Valley, CA; elevation: 1890 m). We present data as mean ± SD and confirmed normality using Shapiro-Wilk tests (α ≥ 0.05). We used simple linear regression to assess the relationship between age and systolic BP (SBP), diastolic BP (DBP), and cfPWV. We compared individual cfPWV outcomes to available normative data. RESULTS: Among 72 WSER athletes, age (46 ± 10 years; range: 26-69 yrs), SBP (129 ± 9 mmHg), DBP (78 ± 7 mmHg), and cfPWV (n = 70; 6.5 ± 1.0 m/s) were normally distributed (Ws ≥ 0.97, Ps ≥ 0.06). Approximately 60% (43/72) of the athletes presented with hypertension (≥130mmHg SBP and/or \u3e80 mmHg DBP) but age was not associated with SBP (R2 = 0.02, P = 0.23) or DBP (R2 = 0.05, P = 0.06). Age was positively associated with cfPWV (R2 = 0.25, P \u3c 0.001) but 84% (59/70) of participants had cfPWV values below their age-predicted value (mean difference: -0.9 m/s). CONCLUSIONS: Among these WSER athletes, a majority were hypertensive, but there was not a meaningful relationship between age and BP. Moreover, in this sample, the increase in SBP per decade (1.3 mmHg/decade) was much lower compared to previously reported increases among the general population (6.5 mmHg/decade). Despite an age-related increase in cfPWV, 84% of athletes had cfPWV values below their age-predicted value. These findings suggest that ultra-endurance training is associated with preserved CV health across the lifespan via attenuated age-related increases in BP and cfPWV values below age-predicted norms

Synthesis, characterization, and in vivo\textit {in vivo} evaluation of a novel potent autotaxin-inhibitor

The autotaxin-lysophosphatidic acid (ATX-LPA) signaling pathway plays a role in a variety of autoimmune diseases, such as rheumatoid arthritis or neurodegeneration. A link to the pathogenesis of glaucoma is suggested by an overactive ATX-LPA axis in aqueous humor samples of glaucoma patients. Analysis of such samples suggests that the ATX-LPA axis contributes to the fibrogenic activity and resistance to aqueous humor outflow through the trabecular meshwork. In order to inhibit or modulate this pathway, we developed a new series of ATX-inhibitors containing novel bicyclic and spirocyclic structural motifs. A potent lead compound ($IC_{50}$ against ATX: 6 nM) with good $\textit {in vivo}$ PK, favorable $\textit {in vitro}$ property, and safety profile was generated. This compound leads to lowered LPA levels $\textit {in vivo}$ after oral administration. Hence, it was suitable for chronic oral treatment in two rodent models of glaucoma, the experimental autoimmune glaucoma (EAG) and the ischemia/reperfusion models. In the EAG model, rats were immunized with an optic nerve antigen homogenate, while controls received sodium chloride. Retinal ischemia/reperfusion (I/R) was induced by elevating the intraocular pressure (IOP) in one eye to 140 mmHg for 60 min, followed by reperfusion, while the other untreated eye served as control. Retinae and optic nerves were evaluated 28 days after EAG or 7 and 14 days after I/R induction. Oral treatment with the optimized ATX-inhibitor lead to reduced retinal ganglion cell (RGC) loss in both glaucoma models. In the optic nerve, the protective effect of ATX inhibition was less effective compared to the retina and only a trend to a weakened neurofilament distortion was detectable. Taken together, these results provide evidence that the dysregulation of the ATX-LPA axis in the aqueous humor of glaucoma patients, in addition to the postulated outflow impairment, might also contribute to RGC loss. The observation that ATX-inhibitor treatment in both glaucoma models did not result in significant IOP increases or decreases after oral treatment indicates that protection from RGC loss due to inhibition of the ATX-LPA axis is independent of an IOP lowering effect