Regulation of NOS expression in vascular diseases

doi:10.52586/4926

Cited by 29 publications

(14 citation statements)

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“… 37 In addition, NO generated by endothelial NOS3 spread into vascular smooth muscle cells, thus leading to relaxation of smooth muscle cells and vasodilation. 38 Özmen et al found higher expression of NOS3 intron 4b/4b in AD than in the control group. 39 About 13% of NOS3 knockout mice had spontaneous AD in the sinotubular junction, 40 indicating the important role of NOS3 in AD development.…”

Section: Discussionmentioning

confidence: 96%

Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification

Zheng,

Yang,

Liu

et al. 2024

JIR

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Purpose Immune microenvironment plays an important role in aortic dissection (AD). Therefore, novel immune biomarkers may facilitate AD prevention, diagnosis, and treatment. This study aimed at mining key immune-related genes and relevant mechanisms involved in AD pathogenesis. Patients and Methods Key immune cells in AD were identified by ssGESA algorithm. Next, genes associated with key immune cells were screened by weighted gene coexpression network analysis (WGCNA). Then hub immune genes were picked from protein-protein interaction network of overlapped genes from differential expression and WGCNA analyses by cytohubba plug-in. Their diagnostic potential was evaluated in two independent cohorts from GEO database. In addition, the expressions of hub immune genes were determined by quantitative RT-PCR, immunohistochemistry, and Western blotting in dissected and normal aortic tissues. Results Activated B cells, CD56dim natural killer cells, eosinophils, gamma delta T cells, immature B cells, natural killer cells and type 17 T helper cells were identified as key immune cells in AD. Thereafter, a gene module significantly correlated with key immune cells were found by WGCNA method. Subsequently, KDR, IGF1, NOS3, PECAM1, GAPDH, FLT1, DLL4, CDH5, VWF, and TEK were identified as hub immune cell related genes by PPI network analysis, which may be potential diagnostic markers for AD, as evidenced by ROC curves. Moreover, the decreased expression of VWF in AD was validated at both mRNA and protein levels, and its expression was significantly positive correlated with the marker of smooth muscle cells, ACTA2, in AD. Further immunofluorescent results showed that VWF was colocalized with ACTA2 in aortic tissues. Conclusion We identified key immune cells and hub immune cell-related genes involved in AD. Moreover, we found that VWF was co-expressed with the smooth muscle cell marker ACTA2, indicating the important role of VWF in smooth muscle cell loss in AD pathogenesis.

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Section: Discussionmentioning

confidence: 96%

Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification

Zheng,

Yang,

Liu

et al. 2024

JIR

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“…Furthermore, free radicals, such as superoxide anion, often act as NO scavengers, reducing their bioavailability and impairing vasodilatation. 30 In this regard, Ortiz et al 12 also found a reduction in the activity of NADPH oxidase in the aorta of infarcted rats treated with thyroid hormones, while De Castro et al 11 showed that TH administration is capable of reducing ROS in the heart of infarcted rats. In terms of total ROS levels, however, the present study did not find differences among groups.…”

Section: Discussionmentioning

confidence: 99%

“…Além disso, os radicais livres, como o ânion superóxido, muitas vezes atuam como sequestradores de NO, reduzindo sua biodisponibilidade e prejudicando a vasodilatação. 30 Nesse sentido, Ortiz et al 12 também observaram uma redução na atividade da NADPH oxidase na aorta de ratos infartados tratados com hormônios tireoidianos, enquanto De Castro et al 11 mostraram que a administração de TH é capaz de reduzir ROS no coração de ratos infartados. Porém, em termos de níveis totais de ROS, o presente estudo não observou diferenças entre os grupos.…”

Section: Discussionunclassified

Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox

Pederiva,

Castro,

Belló-Klein

et al. 2024

Arq. Bras. Cardiol.

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Resumo Fundamento A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva (“redox”), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. Objetivos Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. Métodos Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. Resultados A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. Conclusão A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.

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“…Our data indicate that only LASSBio-2039 reduced the NO production by activated macrophages. After 8 h of activation with LPS, there is a peak in the expression of the iNOS enzyme and that, despite this, the production of NO and this production remains for 24 h [ 36 ]. So, we evaluated the effect of LASSBios on NO production after 8 h of LPS activation; however, none of the LASSBios affected NO production.…”

Section: Discussionmentioning

confidence: 99%

Novel Regioisomeric Analogues of Naphthyl-N-Acylhydrazone Derivatives and Their Anti-Inflammatory Effects

Salomé

Freitas

Fraga

et al. 2022

IJMS

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Background: When homeostasis is disturbed it can result in a pathological event named inflammation. The main drugs used in the treatment consist of non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this study, we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effects in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios affected inducible nitric oxide synthase activity nor presented nitric oxide (NO) scavenger effect. No toxic effect was observed, either in vivo or in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented significant anti-inflammatory activity, suggesting LASSBio-2039 has a direct effect in leukocytes migratory capacity. Conclusions: Taken together, the data indicate that these substances present promising effects for the development of a prototype for new drugs.

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Regulation of NOS expression in vascular diseases

Cited by 29 publications

References 184 publications

Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification

Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification

Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox

Novel Regioisomeric Analogues of Naphthyl-N-Acylhydrazone Derivatives and Their Anti-Inflammatory Effects

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