Since the identification of the alternative angiotensin converting enzyme (ACE)2/Ang-(1-7)/Mas receptor axis, renin-angiotensin system (RAS) is a new complex target for a pharmacological intervention. We investigated the expression of RAS components in the heart and kidney during the development of hypertension and its perinatal treatment with losartan in young spontaneously hypertensive rats (SHR). Expressions of RAS genes were studied by the RT-PCR in the left ventricle and kidney of rats: normotensive Wistar, untreated SHR, SHR treated with losartan since perinatal period until week 9 of age (20 mg/kg/day) and SHR treated with losartan only until week 4 of age and discontinued until week 9. In the hypertrophied left ventricle of SHR, cardiac expressions of Ace and Mas were decreased while those of AT1 receptor (Agtr1a) and Ace2 were unchanged. Continuous losartan administration reduced LV weight (0.43 ± 0.02; P < 0.05 versus SHR) but did not influence altered cardiac RAS expression. Increased blood pressure in SHR (149 ± 2 in SHR versus 109 ± 2 mmHg in Wistar; P < 0.05) was associated with a lower renal expressions of renin, Agtr1a and Mas and with an increase in ACE2. Continuous losartan administration lowered blood pressure to control levels (105 ± 3 mmHg; P < 0.05 versus SHR), however, only renal renin and ACE2 were significantly up-regulated (for both P < 0.05 versus SHR). Conclusively, prevention of hypertension and LV hypertrophy development by losartan was unrelated to cardiac or renal expression of Mas. Increased renal Ace2, and its further increase by losartan suggests the influence of locally generated Ang-(1-7) in organ response to the developing hypertension in SHRs.
- MeSH
- angiotensin konvertující enzym metabolismus MeSH
- hypertenze komplikace farmakoterapie genetika prevence a kontrola MeSH
- hypertrofie levé komory srdeční komplikace farmakoterapie genetika prevence a kontrola MeSH
- ledviny účinky léků enzymologie MeSH
- losartan aplikace a dávkování farmakologie terapeutické užití MeSH
- messenger RNA genetika metabolismus MeSH
- myokard enzymologie MeSH
- novorozená zvířata MeSH
- oxid dusnatý metabolismus MeSH
- potkani inbrední SHR MeSH
- protoonkogenní proteiny metabolismus MeSH
- receptory spřažené s G-proteiny metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- renin-angiotensin systém účinky léků genetika MeSH
- signální transdukce účinky léků MeSH
- srdeční komory účinky léků metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Úvod a ciele: Svetlobunkový renálny karcinóm (CCRCC) predstavuje až 75-80 % všetkých histologických podtypov, a tak je najčastejšie sa vyskytujúcim podtypom adenokarcinómu obličiek. Tkanivová hypoxia je výsledkom nerovnováhy v zásobení tkanív kyslíkom a jeho metabolickej spotrebe. Hypoxia vedie k aktivácii viacerých génov kódujúcich proteíny, ktoré sa zúčastňujú na procesoch angiogenézy, erytropoézy a glukózovom metabolizme. Cieľom práce bolo sledovať expresiu erytropoetínu (EPO) v tumorových tkanivách za hypoxických podmienok, so zámerom poukázať na jeho možnú úlohu pri rozvoji svetlobunkového adenokarcinómu obličiek. Materiál a metódy: Pacientom po radikálnej nefrektómii boli odobraté tumorové a kontrolné tkanivá, v ktorých sa sledovali zmeny v expresii HIF-1α prostredníctvom imunoblotovej analýzy a expresia EPO a EPOR metódou RT-PCR. Výsledky: Nezaznamenali sme zmeny v expresii HIF-1α ani v expresii EPOR v tumorových tkanivách v porovnaní s kontrolnými. Metódou RT-PCR sme stanovili aj expresiu EPO, kde naše výsledky poukázali na zvýšenú expresiu EPO v tumoroch v porovnaní s kontrolnými tkanivami. Záver: Zatiaľ nie je známa funkcia nadmerne produkovaného EPO bunkami v CCRCC, keďže iba u 5 % pacientov s RCC je zaznamenaná erytrocytóza. Nadmerná produkcia EPO v bunkách CCRCC pravdepodobne súvisí s jeho proangiogénnymi, antiapoptotickými a proliferačnými procesmi počas tumorigenézy nádorového ochorenia.
Introduction and objectives: Clear cell renal cell carcinoma (CCRCC) represents 75-80 % of all histological subtypes and it is the most commonly occurring subtype of renal adenocarcinoma. Tissue hypoxia is the result of an imbalance in the supply of oxygen to the tissues, and its metabolic consumption. Hypoxia leads to activation of several genes encoding proteins involved in angiogenesis, erythropoiesis, and glucose metabolism. Aim of this study was to investigate the expression of erythropoietin (EPO) in tumour tissue after hypoxic conditions, with the aim to highlight its role in the development of clear cell renal cell carcinoma. Material and methods: In patients after radical nephrectomy tumour and control tissues were sampled, in which there were monitored changes in the expression of HIF-1α by immunoblot analysis and expression of EPO and EPOR using RT-PCR method. Results: We have observed neither change in HIF-1α expression nor in EPOR expression in tumour tissue compared with control one. By RT-PCR method we determined the expression of EPO, where our results showed an increased expression of EPO in tumours compared to control tissue. Conclusion: The function of EPO overexpression by cells in CCRCC has not been known yet, as only in 5 % of patients with RCC erythrocytosis is reported. The excessive EPO production in CCRCC cells is probably related to its proangiogenic, antiapoptotic and proliferative processes during tumourigenesis in neoplastic diseases.
Úvod a ciele: Adenokarcinóm obličiek (RCC – renal cell carcinoma) je najbežnejším nádorovým ochorením obličiek a tvorí 3 % zo všetkých nádorových ochorení. Pacienti sú pri stanovení diagnózy často v pokročilom štádiu ochorenia a až 20-30 % pacientov je postihnutých metastázami. Materiál a metódy: Pacientom po radikálnej nefrektómii boli odobraté tumorové a kontrolné tkanivá, v ktorých sa sledovali zmeny expresie kaveolínu-1 (Cav-1) prostredníctvom metódy western blot a imunohistochémie (ICC). Zmeny expresie boli porovnané s TNM klasifikáciou a Fuhrmanovej nukleárnym gradingom tumorov. Výsledky: V tumorových tkanivách sme pozorovali nadprodukciu Cav-1 v porovnaní s kontrolným tkanivom. Súbor pacientov sme rozdelili podľa TNM klasifikácie do skupín T1a, T1b, T3a a T3b a podľa Fuhrmanovej nukleárneho gradingu do skupín G1, G2 a G3. Zaznamenali sme zvýšenú expresiu Cav-1 v T1a stupni TNM klasifikácie a v G1 stupni Fuhrmanovej gradingu v porovnaní s kontrolou. Záver: Cav-1 sa môže podieľať na rozvoji nádorovej masy. Jeho vysoké hladiny by mohli slúžiť ako indikátor závažnosti ochorenia adenokarcinómu obličiek.
Introduction and objectives: Renal cell carcinoma is the most common malignant disease of the kidney. It accounts for 3 % of all adult malignancies. The 20-30 % of patients are often diagnosed with metastatic disease. Material and methods: Samples of tumor and healthy tissues obtained from patients by radical nephrectomy were used to determine the expression of Cav-1 by western blot and immunohistochemistry. Changes of the expression level were correlated with TNM classification and Fuhrman nuclear grading of the tumors. Patients were divided into groups according to TNM classification and Fuhrman´s grading. Results: We observed over-expression of Cav-1 in the stages T1a of TNM and G1 of Fuhrman´s grading. Conclusion: Cav-1 may participate in the growth of tumors cell and angiogenesis and could be used as a biomarker of renal cell carcinoma.
