Adapting Technological Interventions to Meet the Needs of Priority Populations

Cardiovascular diseases (CVD) comprise the leading cause of mortality worldwide, accounting for 3 in 10 deaths. Individuals with certain risk factors, including tobacco use, obesity, low levels of physical activity, type 2 diabetes mellitus, racial/ethnic minority status and low socioeconomic status, experience higher rates of CVD and are, therefore, considered priority populations. Technological devices such as computers and smartphones are now routinely utilized in research studies aiming to prevent CVD and its risk factors, and they are also rampant in the public and private health sectors. Traditional health behavior interventions targeting these risk factors have been adapted for technology-based approaches. This review provides an overview of technology-based interventions conducted in these priority populations as well as the challenges and gaps to be addressed in future research. Researchers currently possess tremendous opportunities to engage in technology-based implementation and dissemination science to help spread evidence-based programs focusing on CVD risk factors in these and other priority populations

Epigenetic control of microsomal prostaglandin E synthase-1 by HDAC-mediated recruitment of p300

Nonsteroidal anti-inflammatory drugs are the most widely used medicine to treat pain and inflammation, and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. HDAC inhibition (HDACi) with the pan-HDAC inhibitor, vorinostat, attenuated prostaglandin (PG)E2 generation in the murine vasculature and in human vascular smooth muscle cells. In line with this, the expression of the key enzyme for PGE2 synthesis, microsomal PGE synthase-1 (PTGES1), was reduced by HDACi. Accordingly, the relaxation to arachidonic acid was decreased after ex vivo incubation of murine vessels with HDACi. To identify the underlying mechanism, chromatin immunoprecipitation (ChIP) and ChIP-sequencing analysis were performed. These results suggest that HDACs are involved in the recruitment of the transcriptional activator p300 to the PTGES1 gene and that HDACi prevented this effect. In line with the acetyltransferase activity of p300, H3K27 acetylation was reduced after HDACi and resulted in the formation of heterochromatin in the PTGES1 gene. In conclusion, HDAC activity maintains PTGES1 expression by recruiting p300 to its gene

Long-term physical activity outcomes in the Seamos Activas II trial.

Latinas report disproportionately low physical activity (PA) levels and related health conditions. Reducing chronic disease in Latinas requires interventions to increase and maintain health-enhancing PA levels; yet limited intervention studies have examined PA maintenance among Latinas. The present study evaluated the efficacy during the maintenance phase (months 6-12) of the Enhanced PA intervention for Latina adults in Seamos Activas II compared to the Original PA Intervention. Seamos Activas II was conducted in San Diego, California from 2015 to 2020. Underactive adult Latina women (N = 199), mainly of Mexican descent (89%) were randomized to the original intervention or a theory- and technology-enhanced intervention. Their PA was measured objectively (via accelerometers) and via self-report at baseline, 6, and 12 months. Quantile regression models assessed treatment effects on min/week of moderate to vigorous PA (MVPA) at 12 months. Generalized linear models examined treatment effects on indicators of meeting 2008 National PA Guidelines. Both groups maintained the significant gains in MVPA they had made during the first 6 months of the intervention, neither increasing nor decreasing their MVPA over the maintenance period, with no significant between-group differences. At 12 months, 46.3% of Enhanced Intervention participants were meeting self-reported PA guidelines (vs 35.6 % of the Original PA Intervention arm, p = .02). Even with minimal contact throughout the maintenance phase, participants maintained their MVPA, which underscores the importance of continued use of evidence-based behavior change tools and techniques to reinforce newly established habits. Theoretical and technological enhancements may help Latinas to continue meeting PA guidelines during maintenance periods

Randomized Trial of a Physical Activity Intervention for Latino Men: Activo

IntroductionLatino men experience disproportionately high rates of diseases related to low physical activity, yet they are poorly represented in physical activity intervention trials. Efforts to promote physical activity in Latina women show promising results, yet such interventions are yet to be extended to Latino men. This study tested a computer expert system‒tailored, text messaging-supported physical activity intervention for underactive Spanish-speaking Latino men compared with a control group matched for contact time. Potential predictors of intervention success were also explored.Study designRandomized trial. Participants were randomized to receive a Tailored Physical Activity Intervention (Intervention) or a Wellness Control (Control). Data were collected in 2015-2017 and analyzed in 2018-2019.Setting/participantsInsufficiently active Latino men (n=46).InterventionIntervention participants received a baseline counseling session and then, individually tailored print materials and text messages on a tapered schedule for 6 months. Control participants received printed wellness materials and text messages on the same schedule.Main outcome measuresPrimary outcome was a change in weekly moderate to vigorous physical activity from baseline to 6 months measured by accelerometers. Self-reported moderate to vigorous physical activity measured by the 7-day Physical Activity Recall Interview was a secondary outcome.ResultsFor Intervention participants, median accelerometer-measured moderate to vigorous physical activity increased from 10.0 minutes/week at baseline to 57.5 minutes/week at 6 months, whereas for Control participants, it increased from 21.0 minutes/week at baseline to 23.0 minutes/week at 6 months (p<0.05). Similar results were found for self-reported moderate to vigorous physical activity. At 6 months, 47% of Intervention participants met national guidelines of 150 minutes/week versus 25% of Control participants (p=0.15, not significant).ConclusionsFindings suggest that an individually tailored intervention can successfully increase moderate to vigorous physical activity in underactive Latino men. Such technology-supported interventions have the potential for broad dissemination.Trial registrationThis study is registered at www.clinicaltrials.gov NCT02512419

The polarity protein Scrib limits atherosclerosis development in mice

AIMS: The protein Scrib (Scribble 1) is known to control apico-basal polarity in epithelial cells. The role of polarity proteins in the vascular system remains poorly characterized; however, we previously reported that Scrib maintains the endothelial phenotype and directed migration. On this basis, we hypothesized that Scrib has anti-atherosclerotic functions. METHODS AND RESULTS: Tamoxifen-induced Scrib-knockout mice were crossed with ApoE-/- knockout mice and spontaneous atherosclerosis under high-fat diet, as well as accelerated atherosclerosis in response to partial carotid artery ligation and high-fat diet, was induced. Deletion of Scrib resulted in increased atherosclerosis development in both models. Mechanistically, flow- as well as acetylcholine-induced endothelium-dependent relaxation and AKT phosphorylation was reduced by deletion of Scrib, whereas vascular permeability and leukocyte extravasation were increased after Scrib knockout. Scrib immune pull down in primary carotid endothelial cells and mass spectrometry identified Arhgef7 (Rho Guanine Nucleotide Exchange Factor 7, βPix) as interaction partner. Scrib or Arhgef7 downregulation by siRNA reduced the endothelial barrier function in HUVEC. Gene expression analysis from murine samples and from human biobank material of carotid endarterectomies indicated that loss of Scrib resulted in endothelial dedifferentiation with a decreased expression of endothelial signature genes. CONCLUSIONS: By maintaining a quiescent endothelial phenotype, the polarity protein Scrib elicits antiatherosclerotic functions

Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells

Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a causal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipoproteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2-controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis.DFG Excellence Cluster "Cardiopulmonary System-ECCPS" [SFB 1039, IRTG1874/2, SFB 1118]; German Center for Cardiovascular Research DZHK; Faculty of Medicine, Goethe University, Frankfurt am Main, Germany; NIH [U01HG008451]; US National Institutes of Health [HL30568, HL095070]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]