Valsartan has the potential to attenuate neointimal hyperplasia and to suppress the inflammatory response. This study aimed to evaluate the role of valsartan in neointimal hyperplasia and the toll-like receptor 4 (TLR4)-nitric oxide synthase (NOS) pathway in the balloon-injured rat aorta.Forty-eight Wistar rats were randomly allocated to three groups: sham control (control), balloon-injured group (surgery), and balloon-injured+valsartan-treated group (valsartan). Rats were killed at 14 and 28 days after balloon-injury, and then the aortic tissues were collected for morphometric analysis as well as for measurements of the mRNA or protein expression of angiotensin II, angiotensin II type 1 (AT1) receptor, angiotensin II type 2 (AT2) receptor, TLR4, endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), serine/arginine-rich splicing factor 1(SRSF1) and extracellular signal regulated kinase (ERK). Valsartan at a dose of 20 mg/kg/day markedly decreased neointimal hyperplasia in the aorta of balloon-injured rats, and significantly reduced the mRNA or protein expression of TLR4, AT1 receptor, SRSF1 and phosphorylated-ERK (p-ERK) as well as the aortic levels of iNOS (all p < 0.05). Moreover, valsartan increased the eNOS level and AT2 receptor mRNA and protein expression levels (all p < 0.05). Valsartan prevented neointimal hyperplasia and inhibited SRSF1 expression and the TLR4-iNOS-ERK-AT1 receptor pathway in the balloon-injured rat aorta.

• MeSH
• aorta účinky léků   enzymologie   patologie   MeSH
• blokátory receptorů AT1 pro angiotensin II farmakologie   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• fosforylace MeSH
• hyperplazie MeSH
• modely nemocí na zvířatech MeSH
• nemoci aorty farmakoterapie   enzymologie   genetika   patologie   MeSH
• neointima * MeSH
• poranění cév farmakoterapie   enzymologie   genetika   patologie   MeSH
• potkani Wistar MeSH
• receptor angiotensinu typ 1 genetika   metabolismus   MeSH
• serin-arginin sestřihové faktory metabolismus   MeSH
• signální transdukce MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• toll-like receptor 4 genetika   metabolismus   MeSH
• valsartan farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIMS: Increased plasma levels of soluble endoglin (sEng) were detected in patients with endothelial dysfunction-related disorders and hypercholesterolemia. In this study, we hypothesized that high levels of sEng accompanied by mild hypercholesterolemia could aggravate endothelial and vessel wall dysfunction and affect endoglin/eNOS signaling in mouse aorta. METHODS: Three-month-old female transgenic mice on CBAxC57BL/6J background, with high levels of sEng (Sol-Eng+high HFD), and their littermates with low levels of sEng (Sol-Eng+low HFD), were fed a high fat diet for six months. Plasma samples were used for biochemical, ELISA and Luminex analyses of total cholesterol, sEng and inflammatory markers. Functional parameters of aorta were assessed with wire myograph 620M. Western blot analyses of membrane endoglin/eNOS signaling and endothelial dysfunction/inflammation markers in aorta were performed. RESULTS: Functional analysis of aorta showed impaired KCl induced vasoconstriction, endothelial-dependent relaxation after the administration of acetylcholine as well as endothelial-independent relaxation induced by sodium nitroprusside in the Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. Ach-induced vasodilation after administration of l-NAME was significantly higher in the Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. The expression of endoglin, p-eNOS/eNOS, pSmad2/3/Smad2/3 signaling pathway was significantly lower in the Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. CONCLUSIONS: The results indicate that long-term hypercholesterolemia combined with high levels of sEng leads to the aggravation of endothelial and vessel wall dysfunction in aorta, with possible alterations of the membrane endoglin/eNOS signaling, suggesting that high levels of soluble endoglin might be considered as a risk factor of cardiovascular diseases.

• MeSH
• aorta metabolismus   patologie   patofyziologie   MeSH
• ateroskleróza genetika   metabolismus   patologie   patofyziologie   MeSH
• cévní endotel metabolismus   patologie   patofyziologie   MeSH
• dieta s vysokým obsahem tuků MeSH
• endoglin genetika   metabolismus   MeSH
• fosforylace MeSH
• hypercholesterolemie komplikace   etiologie   MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• nemoci aorty genetika   metabolismus   patologie   patofyziologie   MeSH
• protein Smad2 metabolismus   MeSH
• protein Smad3 metabolismus   MeSH
• signální transdukce MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• upregulace MeSH
• vazodilatace MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• genetické testování * metody   MeSH
• geny MeSH
• hypertenze genetika   klasifikace   patofyziologie   MeSH
• kardiologie * metody   MeSH
• kardiomyopatie genetika   klasifikace   patologie   MeSH
• kardiovaskulární nemoci genetika   klasifikace   patologie   MeSH
• lidé MeSH
• nemoci aorty genetika   klasifikace   patologie   MeSH
• srdeční arytmie genetika   klasifikace   patologie   MeSH
• vrozené srdeční vady etiologie   genetika   klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

AIMS: A soluble form of endoglin (sEng) was proposed to participate in the induction of endothelial dysfunction in small blood vessels. Here, we tested the hypothesis that high levels of sEng combined with a high-fat diet induce endothelial dysfunction in an atherosclerosis-prone aorta. METHODS AND RESULTS: Six-month-old female and male transgenic mice overexpressing human sEng (Sol-Eng+) with low (Sol-Eng+low) or high (Sol-Eng+high) levels of plasma sEng were fed a high-fat rodent diet containing 1.25% cholesterol and 40% fat for 3 months. The plasma cholesterol and mouse sEng levels did not differ in the Sol-Eng+high and Sol-Eng+low mice. The expression of proinflammatory (P-selectin, ICAM-1, pNFκB and COX-2) and oxidative-stress-related markers (HO-1, NOX-1 and NOX-2) in the aortas of Sol-Eng+high female mice was significantly higher than in Sol-Eng+low female mice. Endothelium-dependent vasodilatation induced by acetylcholine was preserved better in the Sol-Eng+ high female mice than in the Sol-Eng+low female mice. CONCLUSION: These results suggest that high concentrations of sEng in plasma in combination with a high-fat diet induce the simultaneous activation of proinflammatory, pro-oxidative and vasoprotective mechanisms in mice aorta and the balance of these biological processes determines whether the final endothelial phenotype is adaptive or maladaptive.

• MeSH
• aorta účinky léků   metabolismus   patofyziologie   MeSH
• ateroskleróza krev   genetika   metabolismus   patofyziologie   MeSH
• biologické markery metabolismus   MeSH
• dieta s vysokým obsahem tuků * MeSH
• endoglin krev   genetika   metabolismus   MeSH
• fenotyp MeSH
• fyziologická adaptace MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• nemoci aorty krev   genetika   metabolismus   patofyziologie   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres * MeSH
• upregulace MeSH
• vazodilatace * účinky léků   MeSH
• vazodilatancia farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zánět krev   genetika   metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Neurofibromatosis von Recklinghausen type 1 (NF1) is an autosomal dominant neurocutaneous disorder affecting one in 3 000-4 000 individuals. Mid-aortic syndrome (MAS) is a rare condition characterized by segmental narrowing of abdominal aorta and stenosis of its major branches - mainly renal arteries, including manifestation of renovascular hypertension. MAS can be caused by different diseases, including NF1. MAIN FINDINGS: A 9 years old girl with primary diagnosis of NF1 combined with renovascular hypertension due to MAS, suffered of bilateral optic and chiasm glioma, pubertas praecox, speech disorder, light mental retardation and scoliosis. We have found a mutation in exone 34 of the NF1 gene (17q11.2). Her father has been also diagnosed with NF1 and hypertension developed at early age. He has the same mutation in exone 34 of NF1 gene. The girl is currently treated with conservative antihypertensive medication with positive effect. Bilateral optic and chiasm glioma are asymptomatic at the time and they had been without progress over period of time. Any vascular surgery, neurosurgical and oncological therapy are not indicated at the present time. CONCLUSION: This article is a summary of clinical findings in patient with NF1 due to NF1 gene mutation in exone 34. It confirms the importance of complex multidisciplinar approach to examination and taking care of NF1 patients and their families.

• MeSH
• aorta abdominalis abnormality   patologie   MeSH
• arteria renalis patologie   MeSH
• chiasma opticum patologie   MeSH
• dítě MeSH
• financování organizované MeSH
• gliom genetika   komplikace   patologie   MeSH
• hypertrofie levé komory srdeční genetika   komplikace   MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• mutace MeSH
• nádory zrakového nervu genetika   komplikace   patologie   MeSH
• nemoci aorty genetika   komplikace   patologie   MeSH
• neurofibromatóza 1 MeSH
• neurofibromin 1 genetika   metabolismus   MeSH
• předškolní dítě MeSH
• proteosyntéza MeSH
• renovaskulární hypertenze genetika   komplikace   patologie   MeSH
• stenóza MeSH
• syndrom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH

Obsahem sdělení je kazuistika pacienta ve věku 41 let, kterého jsme přijímali na JIP naší kliniky pro těžké bilaterální srdeční selhání (NYHA IV) při vrozené kombinované aortální vadě s převahou stenózy a suspekci na infekční endokarditidu. Stav byl komplikován akutním renálním selháním prerenální etiologie při nízkém minutovém volumu a anasarkou. Za použití CRRT se nám podařilo pacienta po 5 týdnech stabilizovat, upravit vnitřní prostředí a připravit ho ke kardiochirurgickému výkonu, po němž se mohl vrátit do běžného života.

This casework describes a 41-year-old patient, whom we hospitalized at our Intensive Care Unit with severe bacterial heart failure (NYHA IV). This patient had congenital combine aortal deficiency with prevailing stenosis and suspicion to infective endocarditis. His state was complicated with acute renal impairment of pre-renal etiology with low minute volume and anasarka. We managed to stabilize the patient after 5 weeks with the use of continuous renal replacement therapy, we arranged the internal environment and prepared him for a cardio surgery, which he successfully passed and return to a common life.

• MeSH
• akutní poškození ledvin MeSH
• hemofiltrace metody   MeSH
• lidé MeSH
• náhrada funkce ledvin metody   MeSH
• nemoci aorty genetika   komplikace   MeSH
• srdeční selhání komplikace   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kazuistiky MeSH