The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT 1 ) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/ Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) ra ts served as controls. Both TGR and HanSD rats responded to two weeks' exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT 1 receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of su ppression of ACE/ANG II/AT 1 receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats., V. Hampl, J. Herget, J. Bíbová, A. Baňasová, Z. Husková, Z. Vaňourková, Š. Jíchová, P. Kujal, Z. Vernerová, J. Sadowski, L. Červenka., and Obsahuje bibliografii
Proteinuria has been recently shown to be an independent risk factor for the progression of chronic nephropathies, but the actual mechanisms by which urinary protein load damages renal tissue in humans remain unsolved. Using real-time RT-PCR method we evaluated intrarenal mRNA expression of various cytokines and chemokines in patients with biopsy-proven IgA nephropathy (IgAN, n=11), membranous nephropathy (MN, n=6) and focal and segmental glomerulosclerosis (FSGS, n=6) who exhibited proteinuria over 0.5 g/day. There was a significant positive correlation between the proteinuria extent and the intrarenal RANTES (regulated upon activation normal T cell expressed and secreted) mRNA expression in patients with IgAN, a similar trend was also observed in patients with MN and FSGS. There were no clear relationships between the proteinuria and intrarenal mRNA expression of tumor necrosis factor α, transforming growth factor β1 and monocyte chemoattractant peptide-1. There were no differences in the pattern of cytokine mRNA expression between different glomerulopathies. In conclusion, our results support the hypothesis that lymphocytes, macrophages and their products provoke tissue in jury in response to proteinuria independently of the nature of renal diseases in man., I. Brabcová, K. Kotsch, P. Hřibová, A. Loužecká, K. Bartošová, K. Hyklová, J. Lácha, H.-D. Volk, O. Viklický., and Obsahuje bibliografii a bibliografické odkazy
It is believed that atherogenesis is a multifactorial process, which could already start in utero. Development of atherosclerosis progresses over decades and leads to the cardiovascular morbidity and mortality in adulthood. At present, we have no exact explanation for all the risk factors acting in the pathogenesis of atherosclerosis. This review should provide an overview about the possible role of intrauterine undernutrition in the development of risk factors for cardiovascular disease. Intrauterine undernutrition leads to changes in fetal growth and metabolism and programs later development of some of these risk factors. A number of experimental and human studies indicates that hypertension as well as impaired cholesterol and glucose metabolism are affected by intrauterine growth. Intrauterine undernutrition plays an important role and acts synergistically with numerous genetic and environmental factors in the development of atherosclerosis. There is evidence that undernutrition of the fetus has permanent effects on the health status of human individuals., P. Szitányi, J. Janda, R. Poledne., and Obsahuje bibliografii
Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways., Pei Sun, Rumeng Li, Yingying Meng, Shijun Xi, Qinqi Wang, Xiulan Yang, Xiaochun Peng, Jun Cai., and Obsahuje bibliografii
Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women, mea n age 45.6±14.0 years) into our cross-sectional study. Lp(a) concentrations correlated inversely with TG, AIP, insulin, HOMA, C-peptide, BMI, waist circumference, and number of MS components (p<0.01 for all). Subjects with MS had significantly lower Lp(a) concentrations in comparison with those without the presence of this phenotype (p<0.0001). Serum concentrations of Lp(a) in the lower (1th 3rd) quartiles of insulin and HOMA were significantly higher than in the 4 th quartile of these insulin resistance markers (p<0.001). Odds ratios of having increased markers of IR (TG, HOMA) and MS in top quartile of Lp(a) also indicate inverse association of Lp(a) with IR. The results of our study support an inverse association of Lp(a) levels with IR and MS that precedes overt T2DM diagnosis., H. Vaverková, D. Karásek, M. Halenka, L. Cibíčková, V. Kubíčková., and Obsahuje bibliografii