Video Experimental Relacionado
Updated: Jun 23, 2026
12:43
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 22, 2012
Celecoxib disminuye la expresión del factor del tejido endotelial a través de la inhibición de la fosforilación de la
Jan Steffel1, Matthias Hermann, Helen Greutert
1Cardiovascular Research, Physiology Institute, University of Zurich, Switzerland.
Circulation
|March 30, 2005
Resumen
Celecoxib, a diferencia de otros coxibs, reduce la expresión del factor tisular (TF) en las células aórticas humanas al inhibir JNK. Esto sugiere distintos efectos farmacológicos relevantes para los pacientes con enfermedades cardiovasculares.
Área de la Ciencia:
- Farmacología Cardiovascular Farmacología Cardiovascular
- Biología Molecular Biología Molecular
- Investigación de la trombosis Investigación de la trombosis
Sus antecedentes:
- Los inhibidores selectivos de la ciclooxigenasa-2 (coxibs) pueden aumentar el riesgo trombótico en pacientes cardiovasculares.
- El factor de tejido (TF) está implicado en la patogénesis de la aterosclerosis y la trombosis.
- Investigar los efectos de coxibs en la expresión de TF es crucial para la seguridad del paciente.
Objetivo del estudio:
- Examinar los efectos diferenciales de varios coxibs en la expresión del factor de tejido (TF).
- Para dilucidar los mecanismos moleculares subyacentes a los cambios mediados por coxib en la expresión de TF.
- Evaluar la relevancia clínica de estos hallazgos para pacientes con enfermedades vasculares ateroscleróticas.
Principales métodos:
- Las células endotelial aórticas humanas fueron tratadas con diferentes coxibs (celecoxib, rofecoxib, NS-398).
- El factor de necrosis tumoral alfa (TNF-α) se utilizó para inducir la expresión y la actividad de TF.
- Se emplearon Western blotting e inhibidores específicos (SP600125) para analizar las vías de señalización, incluidas JNK, p38 MAPK y p44/42 MAPK.
Principales resultados:
- Celecoxib disminuyó significativamente la expresión y actividad de TF inducida por el TNF-α.
- Rofecoxib y NS-398 no afectaron la expresión o actividad de TF.
- Celecoxib inhibió la fosforilación de JNK, un mecanismo confirmado por SP600125, mientras que otros coxibs no lo hicieron.
- El efecto del celecoxib en la TF fue independiente de la inhibición de la COX-2.
Conclusiones:
- Celecoxib exhibe una capacidad única para reducir la expresión y la actividad de TF en las células endoteliales.
- Este efecto está mediado por la inhibición de la fosforilación de JNK, no por la inhibición de COX-2.
- Existe una heterogeneidad significativa entre los coxibs con respecto a su impacto en la TF, con posibles implicaciones clínicas para las enfermedades cardiovasculares y ateroscleróticas.
Videos de Conceptos Relacionados
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...