Angiopoietin-1 enhances neutrophil chemotaxis in vitro and migration in vivo through interaction with CD18 and release of CCL4.

Angiopoietins are a family of growth factors that are ligands for the tyrosine kinase receptor, Tie2. Angiopoietin 1 (Ang-1) is agonistic for Tie2, plays a key role in blood vessel maturation and stability and has been shown to possess anti-inflammatory properties. However, Tie2 expression has been demonstrated on human neutrophils and the observation that neutrophils migrate in response to Ang-1 in vitro has confounded research into its exact role in inflammation as well as its potential use as a therapeutic agent.

Familial Hypercholesterolemia in Greek children and their families: genotype-to-phenotype correlations and a reconsideration of LDLR mutation spectrum.

Objective: Familial Hypercholesterolemia (FH) is a common lipid metabolism disease, resulting in premature atherosclerosis, even from childhood. We aimed to define the genetic basis of FH in children and their families, to refine the spectrum of Low-Density Lipoprotein Receptor gene (LDLR) mutations and identify genotype-to-phenotype correlations in patients of Greek origin.

Methods: LDLR was analyzed in 561 patients from 262 families, by whole-gene sequencing.

Novel LDLR variants in patients with familial hypercholesterolemia: in silico analysis as a tool to predict pathogenic variants in children and their families.

Familial hypercholesterolemia (FH) is an autosomal dominant disease with a frequency of 1:500 in its heterozygous form. To date, mutations in the low-density lipoprotein receptor gene (LDLR) are the only identified causes of FH in the Greek population, causing high levels of low-density lipoprotein (LDL) and total cholesterol and premature atherosclerosis. The Greek FH population is genetically homogeneous, but most previous studies screened for the most common mutations only.

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis.

Introduction: Severe sepsis is characterised by intravascular or extravascular infection with microbial agents, systemic inflammation and microcirculatory dysfunction, leading to tissue damage, organ failure and death. The growth factor angiopoietin (Ang-1) has therapeutic potential but recombinant Ang-1 tends to aggregate and has a short half-life in vivo. This study aimed to investigate the acute effects of the more stable Ang-1 variant matrilin-1-angiopoietin-1 (MAT.

Structure of the extracellular domain of Tie receptor tyrosine kinases and localization of the angiopoietin-binding epitope.

Angiogenesis is essential for tissue repair and regeneration during wound healing but also plays important roles in many pathological processes including tumor growth and metastasis. The receptor protein tyrosine kinase Tie2 and its ligands, the angiopoietins, have important functions in the regulation of angiogenesis. Here, we report a detailed structural and functional characterization of the extracellular region of Tie2.

A conserved trimerization motif controls the topology of short coiled coils.

In recent years, short coiled coils have been used for applications ranging from biomaterial to medical sciences. For many of these applications knowledge of the factors that control the topology of the engineered protein systems is essential. Here, we demonstrate that trimerization of short coiled coils is determined by a distinct structural motif that encompasses specific networks of surface salt bridges and optimal hydrophobic packing interactions.

The major human structural IgE epitope of the Brazil nut allergen Ber e 1: a chimaeric and protein microarray approach.

A protein microarray system containing different dilutions of 77 related and non-related proteins was used to show that IgE from subjects allergic to Brazil nut specifically recognise the seed 2S albumin protein (Ber e 1). Further, correctly folded chimaeric 2S albumin proteins containing structural epitope replacement were constructed and directed to the secretion pathway of the methylotropic yeast Pichia pastoris. Through the use of a chimaeric protein microarray system together with sera from a panel of 18 well-characterised Brazil nut allergic subjects, a structural IgE epitope of Ber e 1 was mapped to a helix-loop-helix region.