Background Dietary interventions may play a role in secondary cardiovascular prevention. hsCRP (High‐sensitivity C‐reactive protein) is a marker of risk for major adverse cardiovascular outcomes in coronary artery disease. Methods and Results The open‐label, blinded end‐point, EVADE CAD (Effects of a Vegan Versus the American Heart Association‐Recommended Diet in Coronary Artery Disease) trial randomized participants (n=100) with coronary artery disease to 8 weeks of a vegan or American Heart Association–recommended diet with provision of groceries, tools to measure dietary intake, and dietary counseling. The primary end point was high‐sensitivity C‐reactive protein. A linear regression model compared end points after 8 weeks of a vegan versus American Heart Association diet and adjusted for baseline concentration of the end point. Significance levels for the primary and secondary end points were set at 0.05 and 0.0015, respectively. A vegan diet resulted in a significant 32% lower high‐sensitivity C‐reactive protein (β, 0.68, 95% confidence interval [0.49–0.94]; P =0.02) when compared with the American Heart Association diet. Results were consistent after adjustment for age, race, baseline waist circumference, diabetes mellitus, and prior myocardial infarction (adjusted β, 0.67 [0.47–0.94], P =0.02). The degree of reduction in body mass index and waist circumference did not significantly differ between the 2 diet groups (adjusted β, 0.99 [0.97–1.00], P =0.10; and adjusted β, 1.00 [0.98–1.01], P =0.66, respectively). There were also no significant differences in markers of glycemic control between the 2 diet groups. There was a nonsignificant 13% reduction in low‐density lipoprotein cholesterol with the vegan diet when compared with the American Heart Association diet (adjusted β, 0.87 [0.78–0.97], P =0.01). There were no significant differences in other lipid parameters. Conclusions In patients with coronary artery disease on guideline‐directed medical therapy, a vegan diet may be considered to lower high‐sensitivity C‐reactive protein as a risk marker of adverse outcomes. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02135939.

BackgroundMultiple sclerosis (MS) is a progressively debilitating neurological condition in which the immune system abnormally erodes the myelin sheath insulating the nerves. Mesenchymal stem cells (MSC) have been used in the last decade to safely treat certain immune and inflammatory conditions.MethodsA safety and feasibility study was completed on the use of umbilical cord MSC (UCMSC) as a treatment for MS. In this 1-year study, consenting subjects received seven intravenous infusions of 20 × 106 UCMSC over 7 days. Efficacy was assessed at baseline, 1 month and 1 year after treatment, including magnetic resonance imaging (MRI) scans, Kurtzke Expanded Disability Status Scale (EDSS), Scripps Neurological Rating Scale, Nine-Hole Peg Test, 25-Foot Walk Test, and RAND Short Form-36 quality of life questionnaire.ResultsTwenty subjects were enrolled in this study. No serious adverse events were reported. Of the mild AEs denoted as possibly related to treatment, most were headache or fatigue. Symptom improvements were most notable 1 month after treatment. Improvements were seen in EDSS scores (p < 0.03), as well as in bladder, bowel, and sexual dysfunction (p < 0.01), in non-dominant hand average scores (p < 0.01), in walk times (p < 0.02) and general perspective of a positive health change and improved quality of life. MRI scans of the brain and the cervical spinal cord showed inactive lesions in 15/18 (83.3%) subjects after 1 year.ConclusionsTreatment with UCMSC intravenous infusions for subjects with MS is safe, and potential therapeutic benefits should be further investigated.Trial registration ClinicalTrials.gov NCT02034188. Registered Jan 13, 2014. https://clinicaltrials.gov/ct2/show/NCT02034188

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The authors identified a heightened platelet activity profile and unraveled a novel immunomodulatory effector role of platelet-derived MRP-14 in reprograming monocyte activation in symptomatic PAD. (Platelet Activity in Vascular Surgery and Cardiovascular Events [PACE]; NCT02106429; and Platelet Activity in Vascular Surgery for Thrombosis and Bleeding [PIVOTAL]; NCT01897103).

Objective Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet–endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. Approach and Results Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.1±12.8 years; 82% female; 37% white) with age- and sex-matched controls. Platelets were coincubated with human umbilical vein endothelial cells (HUVECs) and changes to gene expression assessed by an RNA array and quantitative reverse transcription polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1±3.9). Compared with controls, patients with SLE had significantly increased monocyte and leukocyte–platelet aggregation and platelet aggregation in response to submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with SLE platelets found a platelet-mediated effect on endothelial gene pathways involved in cell activation. Sera from SLE versus control subjects significantly increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3) platelet-induced HUVEC gene expression of interleukin-8, and intercellular adhesion molecule 1; and (4) proinflammatory gene expression in HUVECs, mediated by interleukin-1β–dependent pathway. Incubation of SLE-activated platelets with an interleukin-1β–neutralizing antibody or HUVECs pretreated with interleukin-1 receptor antibodies attenuated the platelet-mediated activation of endothelial cells. Conclusions Platelet activity measurements and subsequent interleukin-1β–dependent activation of the endothelium are increased in subjects with SLE. Platelet–endothelial interactions may play a role in the pathogenesis of cardiovascular disease in patients with SLE.

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro, and a clinically relevant 1.8 mg oral loading dose administered over one hour in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations, but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28% [22–57] to 22% [19–31], p=0.05) and NPA (19% [16–59] to 15% [11–30], p=0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328–555] to 333 MFI [232–407], p=0.02) and P-selectin (351 MFI [269–492] to 279 [226–364], p=0.03), and platelet adhesion to collagen (10.2% [2.5–32.6] to 2.0% [0.2–9.5], p=0.09) 2 hours post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation, but does not inhibit homotypic platelet aggregation.

Individuals with autism spectrum disorder (ASD) suffer from developmental disabilities that impact communication, behavior, and social interaction. Immune dysregulation and inflammation have been linked to children with ASD, the latter manifesting in serum levels of macrophage‐derived chemokine (MDC) and thymus, and activation‐regulated chemokine (TARC). Mesenchymal stem cells derived from umbilical cord tissue (UC‐MSCs) have immune‐modulatory and anti‐inflammatory properties, and have been safely used to treat a variety of conditions. This study investigated the safety and efficacy of UC‐MSCs administered to children diagnosed with ASD. Efficacy was evaluated with the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS), and with measurements of MDC and TARC serum levels. Twenty subjects received a dose of 36 million intravenous UC‐MSCs every 12 weeks (four times over a 9‐month period), and were followed up at 3 and 12 months after treatment completion. Adverse events related to treatment were mild or moderate and short in duration. The CARS and ATEC scores of eight subjects decreased over the course of treatment, placing them in a lower ASD symptom category when compared with baseline. MDC and TARC inflammatory cytokine levels also decreased for five of these eight subjects. The mean MDC, TARC, ATEC, and CARS values attained their lowest levels 3 months after the last administration. UC‐MSC administration in children with ASD was therefore determined to be safe. Although some signals of efficacy were observed in a small group of children, possible links between inflammation levels and ASD symptoms should be further investigated. Stem Cells Translational Medicine 2019;8:1008–1016

Platelet activity plays a major role in hemostasis with increased platelet activity likely contributing to the pathogenesis of atherothrombosis. We sought to identify associations between platelet activity variability and platelet-related genes in healthy controls. Transcriptional profiling of platelets revealed that WD-40 repeat domain 1 (WDR1), an enhancer of actin-depolymerizing factor activity, is downregulated in platelet messenger RNA (mRNA) from subjects with a hyperreactive platelet phenotype. We used the human megakaryoblastic cell line MEG-01 as an in vitro model for human megakaryocytes and platelets. Stimulation of MEG-01 with thrombin reduced levels of WDR1 transcripts and protein. WDR1 knockdown (KD) in MEG-01 cells increased adhesion and spreading in both the basal and activated states, increased F-actin content, and increased the basal intracellular calcium concentration. Platelet-like particles (PLPs) produced by WDR1 KD cells were fewer in number but larger than PLPs produced from unmodified MEG-01 cells, and had significantly increased adhesion in the basal state and upon thrombin activation. In contrast, WDR1 overexpression reversed the WDR1 KD phenotype of megakaryocytes and PLPs. To translate the clinical significance of these findings, WDR1 expression was measured in platelet RNA from subjects with established cardiovascular disease (n = 27) and age- and sex-matched controls (n = 10). The WDR1 mRNA and protein level was significantly lower in subjects with cardiovascular disease. These data suggest that WDR1 plays an important role in suppressing platelet activity, where it alters the actin cytoskeleton dynamics, and downregulation of WDR1 may contribute to the platelet-mediated pathogenesis of cardiovascular disease.