The Association of Serum Levels of stromolysin-1 and connexin-37 with the severity of coronary artery disease

Background Coronary Artery Disease (CAD) is a common form of heart disease that is considered a serious health problem in society. Atherosclerosis is widely recognized as a chronic inflammatory disease of the vessels and can lead to CAD and myocardial infarction. The aim of the present study was to investigate serum levels of connexin-37 and stromelysin-1 as significant biomarkers of CAD and their correlation with the extent of CAD. Methods and results Sixty CAD patients with one-vessel (1VD), two-vessel (2VD), and three-vessel (3VD) disease were enrolled in this study. For comparison with the results, 20 healthy control subjects were also included in this study. Serum concentrations of connexin-37 and stromelysin-1 were determined using commercial ELISA kits. Serum connexin-37 concentrations were not significantly different between the patient and control groups (p < 0.05). The analysis showed a statistically significant difference between subjects with one-vessel disease, subjects with two-vessel disease, and subjects with three-vessel disease. Serum Stromelysin-1 concentration was significantly higher in the patients than in the control group (p < 0.05). Conclusions The results of our study indicate that serum levels of stromelysin-1, but not connexin-37, may contribute to the prediction of the occurrence and progression of CAD.

The Role of Connexin 37 Polymorphism in Spontaneous Abortion

Among unique cardiovascular risk factors in women are complications during pregnancy, including miscarriage. Important risk factor is also genetic background. One of powerful candidate genes for cardiovascular disease of atherosclerotic origin (aCVD) is gene for connexin 37 (Cx37) with strong gene-environment interaction including smoking status, that is also strong risk factor for complications in pregnancy including spontaneous abortion (SA). We analyzed association between SA and Cx37 gene polymorphism (1019C>T; Pro319Ser) in 547 fetuses and its potential interaction with smoking status of mothers. Using genetic analyses from women from general population as controls, ORs for T allele, found in our previous studies to be protective against aCVD, were calculated. T allele carriers (fetuses), had OR 0.91 (95 % CI 0.72-1.14) and no interaction with smoking was observed. In conclusion, no significant association between Cx37 polymorphism and SA was observed and no modifying effect of smoking status on this association was detected.

Genetic deletion of connexin 37 causes polyuria and polydipsia

The connexin 37 (Cx37) channel is clustered at gap junctions between cells in the renal vasculature or the renal tubule where it is abundant in basolateral cell interdigitations and infoldings of epithelial cells in the proximal tubule, thick ascending limb, distal convoluted tubule and collecting duct; however, physiological data regarding its role are limited. In this study, we investigated the role of Cx37 in fluid homeostasis using mice with a global deletion of Cx37 (Cx37-/- mice). Under baseline conditions, Cx37-/- had ~40% higher fluid intake associated with ~40% lower urine osmolality compared to wild-type (WT) mice. No differences were observed between genotypes in urinary adenosine triphosphate or prostaglandin E2, paracrine factors that alter renal water handling. After 18-hours of water deprivation, plasma aldosterone and urine osmolality increased significantly in Cx37-/- and WT mice; however, the latter remained ~375 mmol/kg lower in Cx37-/- mice, an effect associated with a more pronounced body weight loss despite higher urinary AVP/creatinine ratios compared to WT mice. Consistent with this, fluid intake in the first 3 hours after water deprivation was 37% greater in Cx37-/- vs WT mice. Cx37-/- mice showed significantly lower renal AQP2 abundance and AQP2 phosphorylation at serine 256 than WT mice in response to vehicle or dDAVP, suggesting a partial contribution of the kidney to the lower urine osmolality. The abundance and responses of the vasopressin V2 receptor, AQP3, NHE3, NKCC2, NCC, H+-ATPase, αENaC, γENaC or Na+/K+-ATPase were not significantly different between genotypes. In summary, these results demonstrate that Cx37 is important for body water handling.

Signal molecules as biomarkers of prediction of the premature rupture of membranes (clinicodiagnostic aspects)

One of the most commonly encountered pregnancy complications is the premature rupture of membranes. This pathology results in the increase of frequency of operative delivery, birth traumatism and neonatal complications. The purpose of the research described was verification of key signal molecules, providing integrity of fetal membranes, with subsequent development of possible biomarkers of non-invasive prediction of the premature rupture of membranes. This work presents the comparison studies of expression of VEGF, MMP-9, connexin 37, connexin 40, endorphins, enkephalins, actin, miosin in a buccal epithelium and fetal membranes for 70 patients of the basic group (with premature rupture of membranes) and for 70 patients of the control group (with timely rupture of membranes). Research of fetal membranes and buccal epithelium was carried out by means of primary monoclonal mouse antibodies to the investigated markers. The universal basis set was used as the secondary antibodies, containing of biotinylated anti-mouse immunoproteins. The study of the preparations was carried out in the confocal microscope OLYMPUS FLUOVIEW FV 1000 at the image enlargement of ×400 and ×1000 with use of the system MRC-1024, with the software suite for computer processing OLYMPUS FLUOVIEW 5.0. Statistical processing of the material was carried out with the application of the standard statistical software suite Statistica 10.0. Obtained in a group with the premature rupture of membranes and in a control group were the reliable differences of expression of MMP-9, VEGF, connexin 37 and connexin 40 were. The multifactorial analysis of the indices of expression of signal molecules allowed to discover the high information significance for premature rupture of membranes prediction, matrix metalloproteinase ММP-9, connexin 37 and connexin 40, as well as VEGF. Matrix metalloproteinase ММP-9, connexin 37 and connexin 40, VEGF can be considered as non-invasive markers of premature rupture of membranes prediction.