Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.

Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor's PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1ß, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.

Pacemaker detected active minutes are superior to pedometer-based step counts in measuring the response to physical activity counseling in sedentary older adults.

BACKGROUND: In patients with permanent pacemakers (PPM), physical activity (PA) can be monitored using embedded accelerometers to measure pacemaker detected active hours (PDAH), a strong predictor of mortality. We examined the impact of a PA Counseling (PAC) intervention on increasing activity as measured by PDAH and daily step counts. METHODS: Thirteen patients (average age 80 ± 6 years, 84.6% women) with implanted Medtronic PPMs with a ≤ 2 PDAH daily average were included in this study. Patients were randomized to Usual Care (UC, N = 6) or a Physical Activity Counseling Intervention (PACI, N = 7) groups. Step count and PDAH data were obtained at baseline, following a 12-week intervention, then 12 weeks after intervention completion. Data were analyzed using independent t-tests, Pearson's r, chi-square, and general linear models for repeated measures. RESULTS: PDAH significantly differed by time point for all subject combined (P = 0.01) but not by study group. Subjects with baseline gait speeds of > 0.8 m/sec were responsible for the increases in PDAH observed. Step counts did not differ over time in the entire cohort or by study group. Step count and PDAH significantly correlated at baseline (r = 0.60, P = 0.03). This correlation disappeared by week 12. CONCLUSION(S): PDAH can be used to monitor PA and PA interventions and may be superior to hip-worn pedometers in detecting activity. A significant increase in PA, regardless of treatment group, suggests that patient awareness of the ability to monitor PA through a PPM increases PA in these patients, particularly in patients with gait speeds of < 0.8 m/sec. TRIAL REGISTRATION: ClincalTrials.gov NCT03052829. Date of Registration: 2/14/2017.

Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation.

BACKGROUND: Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. METHODS: Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. RESULTS: Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = - 0.35, P = 0.03). CONCLUSION: Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation.