MicroRNAs in pathophysiology of acute myocardial infarction and cardiogenic shock.

AIM: Levels of circulating miRNA are considered to be potential biomarkers of acute myocardial infarction and disease progression. METHODS: In this study, the expression levels of circulating miRNA-1, miRNA-133 and miRNA-124a were investigated in a group of patients with acute myocardial infarction (STEMI) and cardiogenic shock (CS) compared to controls. RESULTS: During the hospitalization period, miRNA-133 showed a significant up-regulation in the serum of STEMI and CS patients compared to controls, while the expression of miRNA-1 was significantly different only in CS. The expression of miRNA-124 was significantly higher in STEMI and CS. Furthermore, miRNA-1 expression was related to the level of circulating glucose in patients with STEMI. We also found a negative correlation between miRNA-133 and MMP-9 levels. MiRNA-124 expression was significantly related to the level of soluble ST2; the marker correlated to cardiac damage. CONCLUSION: All selected miRNAs are potential markers of cardiac injury in cardiogenic shock, whereas miRNA-124a and -133 are markers of injury in STEMI. MiRNA-1 expression is related to circulating glucose in STEMI. None of miRNAs could be correlated to the extent of injury, progress of the disease, or prognosis of patient outcome. Therefore, the levels of circulating miRNA have no potential for becoming a biomarker of myocardial damage and as such would bring no further benefit compared to current markers (Tab. 4, Fig. 1, Ref. 47).

Early Inflammatory Response in the Brain and Anesthesia Recovery Time Evaluation After Experimental Subarachnoid Hemorrhage.

The main objective was to evaluate, whether the subarachnoid hemorrhage (SAH)-associated early inflammatory response has focal or global character, i.e., whether areas distant to hematoma may be affected by an early inflammatory response. The second objective was to evaluate the association of anesthesia recovery time for basic reflexes/neurological functions with severity of SAH. SAH was induced in rats using an endovascular perforation model. Anesthesia recovery time was evaluated for pain reaction recovery time (spinal level), spontaneous ventilation recovery time (brain stem level), and consciousness recovery time (neocortical level). mRNA expressions of TNFα, IL-1ß, IL-6, ICAM-1, and VCAM-1 in areas adjacent and distant to hematoma were evaluated between 2 and 8 h after SAH. Serum levels of TNFα, IL-1ß, and IL-6 were assessed at 4 and 8 h after SAH. Anesthesia recovery time of all selected parameters was associated with severity of SAH. The consciousness recovery time test had the best predictive value, while the spontaneous ventilation recovery time test was able to bring information in the shortest time. The mRNA expressions of pro-inflammatory cytokines were significantly increased in severe SAH groups in both adjacent and distant areas. The inflammatory response in mild/moderate SAH groups was less strong, peaking at 4 h after SAH. Serum levels of pro-inflammatory cytokines were ambiguous. Anesthesia recovery time may be useful for bleeding severity prediction in the SAH model; however, further validation is needed. Severe subarachnoid hemorrhage is associated with the strong early inflammatory response, which has a global character, while mild subarachnoid hemorrhage is accompanied by a weaker inflammation.

Central pulse pressure and variability in matrix metalloproteinases genes and their inhibitors in patients with ischemic heart disease.

Matrix metalloproteinases (MMPs) as well as their inhibitors (TIMPs) play a crucial role in controlling extracellular matrix turnover and have recently been associated with atherosclerosis, myocardial and vascular injury. Moreover, the genetic variability of MMP genes has been suggested to play an important role in vascular remodeling and age-related arterial stiffening. This study aims to describe associations of 14 selected polymorphisms in genes for MMPs and TIMPs with selected cardiovascular parameters (including central pulse pressure), clinical conditions and drug treatment profiles in 411 stable ischemic patients with preserved systolic function of the left ventricle. The genotyping of 14 single-nucleotide polymorphisms in 8 genes was carried out either using 5´ exonuclease (TaqMan®) reagents or by restriction analysis. Numerous associations of the investigated polymorphisms with systolic and diastolic blood pressure, maximum left ventricular end diastolic pressure and ejection fraction were observed. While some of the observed effects were found to be age-dependent, associations with clinical conditions (hypertension, diabetes mellitus, angina pectoris) were only observed in women and associations with four groups of drugs (statins, nitrates, calcium channel blockers, anti-aggregation drugs) were only observed in men. The results of this study indicate that the genetic variability of MMPs and TIMPs is an important factor which influences cardiovascular functions and may have important consequences for individual therapy customization in the future.

Relation of IL-6, IL-13 and IL-15 gene polymorphisms to the rheumatoid factors, anti-CCP and other measures of rheumatoid arthritis activity.

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL-6, IL-13 and IL-15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti-CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL-6, IL-13 and IL-15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL-15 -267C/T polymorphism. A higher prevalence of heterozygote variants of IL-15 polymorphisms (14035A/T and -267C/T) in the RF IgG- and RF IgA-negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL-15 with circulating level of IL-15 (14035A/T and 367G/A) and with total RF and Ig-specific RFs (-267C/T) was found. The relation of IL-15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL-13 polymorphism -1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL-15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL-15 levels in circulation to RFs.

Importance of the assessment of coenzyme Q10, alpha-tocopherol and oxidative stress for the diagnosis and therapy of infertility in men.

UNLABELLED: Male infertility is one of the most stressful factors of couples, being present in about 40% cases. It is usually caused by a low number of sperm (oligozoospermia) or poor sperm motility (asthenozoospermia). The sperm motility is used as an indicator of semen quality and male infertility. To the impairment of male reproduction health can contribute genetic, nutritional and environmental factors, smoking and drugs. It is well documented that excessive reactive oxygen species (ROS) production decreases sperm motility, impairs sperm function, damages the morphology of spermatozoa (1, 2). To the decreased sperm motility contribute also disturbances of sperm mitochondrial function and energy production, low levels of coenzyme Q10 and carnitine, as well as sperm mitochondrial deoxyribonucleic acid (DNA) defects. The origin of sperm dysfunction, however, is not well understood. BACKGROUND: Oxidative stress has been established as a major factor in the pathogenesis of male infertility. Low level of coenzyme Q10 contributes to the decreased sperm motility, which plays a vital role in sperm mitochondrial energy production and neutralization of reactive oxygen species (ROS).The aim of the present study was to find out, if an assessment of coenzyme Q10-TOTAL (CoQ10-TOTAL), α-tocopherol, γ-tocopherol and oxidative stress could contribute to the diagnosis of infertility in men. SUBJECTS AND METHODS: Two groups of infertile men, according to sperm motility (a+b and b+c) were included in the study. CoQ10-TOTAL, α-tocopherol, γ-tocopherol in plasma and seminal fluid, and parameter of oxidative stress (thiobarbituric acid reactive substances - TBARS) in plasma were determined. RESULTS: Higher sperm density and decreased sperm pathology were found in group a+b vs b+c (class a and b - fast and weak forward motility, class c - nonprogressive motility). Concentrations of CoQ10-TOTAL and α-tocopherol were significantly increased in seminal fluid of groups a+b vs b+c, opposite results were estimated in plasma. Concentrations of γ-tocopherol in plasma and seminal fluid of both groups were similar. Plasmatic TBARS concentrations were increased in both groups of infertile men. CONCLUSION: We suppose that incorporation of oxidative stress assessment, CoQ10-TOTAL and α-tocopherol concentrations in seminal fluid and plasma into routine andrology can play an important role for the diagnosis and targeted therapy of male infertility (Tab. 1, Ref. 16).

Relationship of resistin levels with endometrial cancer risk.

Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p <001). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects.