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Platelet activation plays an essential role in clot formation to prevent blood loss following vascular damage. In pathologic conditions, platelet activation can lead to obstructive clots, disrupting blood flow and resulting in thrombosis. Native Americans suffer disproportionately from arterial disease and previous research has shown that Blacks are enriched in genetic polymorphisms that correlate with higher platelet reactivity contributing to an increased risk for thrombosis. Therefore, the current study sought to determine phenotypic variations in Native American platelet responses following stimulation with agonists, simulating vascular damage. Several donors from a small cohort of Native Americans showed atypical robust platelet aggregation when stimulated with submaximal concentrations of agonists. Further, when comparing α-granule secretion, a specific marker of platelet activation, Native Americans were more likely to have elevated responses to multiple agonist conditions of stimulation compared to Whites. Interestingly, there were no noticeable differences in integrin activation between Native Americans and Whites. Our study is the first to observe elevated Native American platelet responses compared to Whites, supporting further mechanistic studies and investigation of treatment approaches for the prevention of thrombosis. [ABSTRACT FROM AUTHOR]

Ischemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGCs) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network density and glial activity were examined by Gene Set Enrichment Analysis, three-dimensional (3-D) volume imaging, and Western blot and its function in regulating epithelial restitution was assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate (FA), and in vitro by coculture assay. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete lack of coordinated reparative signaling in the mucosal microenvironment. Furthermore, we report important evidence that the subepithelial EGC network changes significantly over the early postnatal period and demonstrate that the proximity of a specific functional population of EGC to wounded intestinal epithelium contributes to intestinal barrier restitution following ischemic injury. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD), principally myocardial infarction (MI) and stroke, is the leading clinical and public health problem in the United States and is rapidly becoming so worldwide. Their primary prevention is promising, in theory, but difficult to achieve in practice. The principal modalities that have demonstrated efficacy include therapeutic lifestyle changes (TLCs) and adjunctive drug therapies under the guidance of the health-care provider and tailored to the individual patient. The prevention and treatment of the pandemic of overweight and obesity and lack of regular physical activity, both of which are alarmingly common in the United States, prevention and treatment of hypertension, avoidance and cessation of cigarette smoking, adoption and maintenance of a healthy diet, and avoidance of heavy alcohol consumption all have proven benefits in decreasing the risks of a first MI and stroke as well as other clinical manifestations of CVD. Although adoption of TLCs would avoid the need for adjunctive drug therapies in many primary prevention subjects, this strategy is difficult to achieve or maintain for most and may be insufficient for many, especially those at high risk with metabolic syndrome. The criteria for metabolic syndrome, affecting over 40% of the adult population older than 40 in the United States, include overweight or obesity, dyslipidemia, hypertension, and insulin resistance, a precursor of diabetes. The adjunctive therapies of proven benefit in the primary prevention of MI and stroke include statins, blood pressure medications, aspirin, and drugs to treat insulin resistance and hyperglycemia. Fortunately, even for patients who prefer prescription of pills to proscription of harmful lifestyles, these drug therapies still have net benefits. The adoption and maintenance of TLCs and adjunctive drug therapies into clinical practice will reduce both the incidence of and mortality from a first MI and stroke as well as other major clinical manifestations of CVD. [ABSTRACT FROM AUTHOR]