Chemokines are a group of about 50 chemotactic cytokines crucial for the migration of immune system cells and tumor cells, as well as for metastasis. One of the 20 chemokine receptors identified to date is CXCR2, a G-protein-coupled receptor (GPCR) whose most known ligands are CXCL8 (IL-8) and CXCL1 (GRO-α). In this article we present a comprehensive review of literature concerning the role of CXCR2 in cancer. We start with regulation of its expression at the transcriptional level and how this regulation involves microRNAs. We show the mechanism of CXCR2 signal transduction, in particular the action of heterotrimeric G proteins, phosphorylation, internalization, intracellular trafficking, sequestration, recycling, and degradation of CXCR2. We discuss in detail the mechanism of the effects of activated CXCR2 on the actin cytoskeleton. Finally, we describe the involvement of CXCR2 in cancer. We focused on the importance of CXCR2 in tumor processes such as proliferation, migration, and invasion of tumor cells as well as the effects of CXCR2 activation on angiogenesis, lymphangiogenesis, and cellular senescence. We also discuss the importance of CXCR2 in cell recruitment to the tumor niche including tumor-associated neutrophils (TAN), tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC), and regulatory T (Treg) cells.

Conduction disturbances, aortic incompetence, and myocardial fibrosis are known complications in adult patients with ankylosing spondylitis (AS). Its incidence has been reported to be 10% to 30%; however, less attention has been paid to all cardiac arrhythmias. The aim of this study was to evaluate arrhythmias and conduction disturbances in patients with AS using electrocardiograms and Holter monitoring (including heart rate variability analysis) and to estimate its relationships with age, gender, clinical features, and duration of AS. Thirty-one patients with AS (20 to 69 years old, mean 50 +/- 14) and 22 healthy volunteers (26 to 69 years old, mean 49 +/- 13) underwent rheumatologic and cardiologic evaluations. Ventricular extrasystoles were present in 55% of AS patients and in 28% of controls. Supraventricular extrasystoles were present in 94% of AS patients and 100% of controls. The frequency of ventricular extrasystoles was found to be higher in the AS patients than in the control subjects. Significant differences were found in heart rate variability analyses: ultra low-frequency power and root mean square recessive difference (r-MSSD) were lower in the AS group. When the AS group was divided into subgroups (stages 3 and 4), significant differences were found between control subjects and stage 3 patients in PR interval, heart rate (HR), T-wave duration, ultra low frequency, and r-MSSD and between controls and stage 4 patients in HR, T-wave duration, and r-MSSD. QTc and QTd were not significantly different in groups and subgroups and were not correlated with any other clinical or electrocardiographic parameter. Cardiac arrhythmias were more frequent in patients with AS than in the healthy population. Simple electrocardiograms and Holter parameters do not correlate with the incidence of VESs, age, gender, clinical features, and duration of AS.

Introduction: Left ventricular mass (LVM) is a strong predictor of various heart diseases. We examine the association between the G(-6)A AGT, I/D ACE, A1166C AGTR1, T(-344)C CYP 11β2, A538G MR and A10631G REN polymorphisms and LVM and blood pressure in newborn infants. Material and methods:The study included 211 healthy newborn infants. Two-dimensional M-mode echocardiography was used to assess LVM between days 3-4 after birth. Polymorphisms were determined by polymerase chain reactionrestriction fragment length polymorphism (PCR-RLFP). Results: AGTR1 genotype was significantly associated with neonatal systolic blood pressure (≥90 percentile). LVM indexes (LVMIs) were tested for association with genotypes in multivariate analysis. The carriers of the A allele of the AGT polymorphism had significantly higher LVM/body length (BL) values when compared with newborn infants homozygous for the G allele (p adjusted =0.03). The higher LVM/BL values were seen in the carriers of the A alleles of the AGTR1 polymorphism (p adjusted =0.046). All examined indexes (LVM/body surface area (BSA), LVM/BL, LVM/bodyweight (BW)) were associated with CYP11B polymorphism. The newborn infants homozygous for the T allele had significantly higher values of LVM/BSA, LVM/ BL, and LVB/BW compared to non-TT-homozygous neonates (p adjusted =0.003; p adjusted =0.003; p adjusted =0.004 respectively). Conclusion: The AGT, AGTR1, CYP11β polymorphisms are associated with increased LVMIs in newborns. This observation indicates that genetic factors may be modulating LVM at birth.

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The members of the family of bone morphogenetic proteins (BMPs) are important regulators in cardiac development. The present study was designed to evaluate the effect of common genetic variants of BMP-4 and its receptors BMPR1A, BMPR1B, and ACVR1 on left ventricular mass (LVM) and other parameters of the heart and blood pressure in newborns. The study included 210 healthy newborns. Two-dimensional M-mode echocardiography was used to assess LVM between days 3 and 4 after birth. Polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism technique. We found lack of associations between LVM, values of blood pressure, and the BMP4, BMPR1A, BMPR1B, and ACVR1 genotypes. A significant association was observed between the 455C allele of BMP4 and increased left ventricular internal diameter systolic (p=0.004) and between 1650T allele of BMPR1B and lower left atrium diameter (p=0.038). Presence of the 455C allele of BMP4 and the 8474T allele of ACVR1 gene was significantly associated with decreased left ventricular ejection fraction (LVEF) (p=0.0004 and p=0.046, respectively). The 455C allele of BMP4 and the 8474T allele of ACVR1 may play a role as significant predictors for decreased LVEF in newborns.