Expression and Function of Osteopontin in Vascular Adventitial Fibroblasts and Pathological Vascular Remodeling

Osteopontin is known to play important roles in various diseases including vascular disorders. However, little is known about its expression and function in vascular adventitial fibroblasts. Adventitial fibroblasts have been shown to play a key role in pathological vascular remodeling associating with various vascular disorders. In this study, we measured activation of Osteopontin and its biological functions in cultured adventitial fibroblasts and injured rat carotid injury arteries induced by balloon angioplasty. Our results showed that angiotensin II and aldosterone increased Osteopontin expression in adventitial fibroblasts in a time- and concentration-dependent manner. MAPKs and AP-1 pathways were involved in Osteopontin upregulation. In addition, Adventitial fibroblast migration stimulated by Angiotensin II and aldosterone required OPN expression. Perivascular delivery of antisense oligonucleotide for Osteopontin suppressed neointimal formation post-injury. We concluded that upregulation of Osteopontin expression in adventitial fibroblasts might be important in the pathogenesis of vascular remodeling after arterial injury

Endothelial progenitor cells and integrins: adhesive needs

In the last decade there have been multiple studies concerning the contribution of endothelial progenitor cells (EPCs) to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute to new vessel formation in adults is termed postnatal vasculogenesis and occurs via four inter-related steps. They must respond to chemoattractant signals and mobilize from the bone marrow to the peripheral blood; home in on sites of new vessel formation; invade and migrate at the same sites; and differentiate into mature endothelial cells (ECs) and/or regulate pre-existing ECs via paracrine or juxtacrine signals. During these four steps, EPCs interact with different physiological compartments, namely bone marrow, peripheral blood, blood vessels and homing tissues. The success of each step depends on the ability of EPCs to interact, adapt and respond to multiple molecular cues. The present review summarizes the interactions between integrins expressed by EPCs and their ligands: extracellular matrix components and cell surface proteins present at sites of postnatal vasculogenesis. The data summarized here indicate that integrins represent a major molecular determinant of EPC function, with different integrin subunits regulating different steps of EPC biology. Specifically, integrin α4β1 is a key regulator of EPC retention and/or mobilization from the bone marrow, while integrins α5β1, α6β1, αvβ3 and αvβ5 are major determinants of EPC homing, invasion, differentiation and paracrine factor production. β2 integrins are the major regulators of EPC transendothelial migration. The relevance of integrins in EPC biology is also demonstrated by many studies that use extracellular matrix-based scaffolds as a clinical tool to improve the vasculogenic functions of EPCs. We propose that targeted and tissue-specific manipulation of EPC integrin-mediated interactions may be crucial to further improve the usage of this cell population as a relevant clinical agent

The effect of deprivation and HbA1c on admission to hospital for diabetic ketoacidosis in type 1 diabetes

Aims/hypothesis: Diabetic ketoacidosis is a potentially life-threatening complication of diabetes and has a strong relationship with HbA1c. We examined how socioeconomic group affects the likelihood of admission to hospital for diabetic ketoacidosis. <p/>Methods: The Scottish Care Information – Diabetes Collaboration (SCI-DC), a dynamic national register of all cases of diagnosed diabetes in Scotland, was linked to national data on hospital admissions. We identified 24,750 people with type 1 diabetes between January 2005 and December 2007. We assessed the relationship between HbA1c and quintiles of deprivation with hospital admissions for diabetic ketoacidosis in people with type 1 diabetes adjusting for patient characteristics. <p/>Results: We identified 23,479 people with type 1 diabetes who had complete recording of covariates. Deprivation had a substantial effect on odds of admission to hospital for diabetic ketoacidosis (OR 4.51, 95% CI 3.73, 5.46 in the most deprived quintile compared with the least deprived). This effect persisted after the inclusion of HbA1c and other risk factors (OR 2.81, 95% CI 2.32, 3.39). Men had a reduced risk of admission to hospital for diabetic ketoacidosis (OR 0.71, 95% CI 0.63, 0.79) and those with a history of smoking had increased odds of admission to hospital for diabetic ketoacidosis by a factor of 1.55 (95% CI 1.36, 1.78). <p/>Conclusions/interpretation: Women, smokers, those with high HbA1c and those living in more deprived areas have an increased risk of admission to hospital for diabetic ketoacidosis. The effect of deprivation was present even after inclusion of other risk factors. This work highlights that those in poorer areas of the community with high HbA1c represent a group who might be usefully supported to try to reduce hospital admissions

Overview and State-of-the-Art of Uncertainty Visualization

International audienceThe goal of visualization is to effectively and accurately communicate data. Visualization research has often overlooked the errors and uncertainty which accompany the scientific process and describe key characteristics used to fully understand the data. The lack of these representations can be attributed, in part, to the inherent difficulty in defining, characterizing, and controlling this uncertainty, and in part, to the difficulty in including additional visual metaphors in a well designed, potent display. However, the exclusion of this information cripples the use of visualization as a decision making tool due to the fact that the display is no longer a true representation of the data. This systematic omission of uncertainty commands fundamental research within the visualization community to address, integrate, and expect uncertainty information. In this chapter, we outline sources and models of uncertainty, give an overview of the state-of-the-art, provide general guidelines, outline small exemplary applications, and finally, discuss open problems in uncertainty visualization