Interaction of p120 with juxtamembrane domain (JMD) of VE-cadherin has been implicated in regulation of endothelial cell-cell adhesion. We used a number of approaches to alter the level of p120 available for binding to VE-cadherin as a means to investigate the role of p120-VE-cadherin interaction in regulation of barrier function in confluent endothelial monolayers. Expression of an epitope-tagged fragment corresponding to JMD of VE-cadherin resulted in a decrease in endothelial barrier function as assessed by changes in albumin clearance and electrical resistance. Binding of JMD-Flag to p120 resulted in a decreased level of p120. In addition to decreasing p120 level, expression of JMD also decreased level of VE-cadherin. Expression of JMD also caused an increase in MLC phosphorylation and rearrangement of actin cytoskeleton, which, coupled with decreased cadherin, can contribute to loss of barrier function. Reducing p120 by siRNA resulted in a decrease in VE-cadherin, whereas increasing the level of p120 increased the level of VE-cadherin, demonstrating that p120 regulates the level of VE-cadherin. Overexpression of p120 was, however, associated with decreased barrier function and rearrangement of the actin cytoskeleton. Interestingly, expression of p120 was able to inhibit thrombin-induced increases in MLC phosphorylation, suggesting that p120 inhibits activation of Rho/Rho kinase pathway in endothelial cells. Excess p120 also prevented JMD-induced increases in MLC phosphorylation, correlating this phosphorylation with Rho/Rho kinase pathway. These findings show p120 plays a major role in regulating endothelial barrier function, as either a decrease or increase of p120 resulted in disruption of permeability across cell monolayers.
Vegetarian diets are associated with several health benefits, but whether a vegetarian or vegan diet is beneficial for athletic performance has not yet been defined. Based on the evidence in the literature that diets high in unrefined plant foods are associated with beneficial effects on overall health, lifespan, immune function, and cardiovascular health, such diets likely would promote improved athletic performance as well. In this article, we review the state of the literature on vegetarian diets and athletic performance, discuss prevention of potential micronutrient deficiencies that may occur in the vegan athlete, and provide strategies on meeting the enhanced caloric and protein needs of an athlete with a plant-based diet.
Type 1diabetes (T1D), in contrast to type 2 diabetes, is an autoimmune disease rather than a lifestyle disease. However, diet and lifestyle factors such as nutrient density, glycemic load, fiber intake, and exercise do affect glycemic control, cardiovascular risk, and risk of complications in patients with type 1 diabetes. Patients with T1D may be able to reduce insulin requirements and achieve better glycemic control if practicing dietary methods to increase plant fibers and micronutrient density, and decrease glycemic load. We propose that anti-inflammatory effects of foods central to a nutrient-dense, plant-rich (NDPR) diet –vegetables, legumes, nuts and seeds, and lower-sugar fruits – may slow or prevent further destruction of beta cells if dietary intervention is initiated early enough. Herein, we present three cases of patients with T1D who have adopted a NDPR diet at varying times following T1D diagnosis. One patient who began a NDPR diet at age 3 immediately following diagnosis has not yet required insulin therapy nearly three years after diagnosis, and has experienced a steady decline in autoantibody levels. Another child who began a NDPR diet several months after diagnosis maintains a low dose of insulin, a favorable HbA1c, and more consistent blood glucose readings. A patient in his mid-40s who began a NDPR diet 13 years after T1D diagnosis, dramatically reduced insulin requirements and C-reactive protein and maintains favorable HbA1c and cardiovascular markers.
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