RESUMEN
An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis in uremic patients, yet its dysfunction poses a significant clinical challenge. Venous stenosis, primarily caused by venous neointimal hyperplasia, is a key factor in the failure of vascular access. During vascular access dysfunction, endothelial cells (ECs) transform mechanical stimuli into intracellular signals and interact with vascular smooth muscle cells. Tanshinone IIA, an important compound derived from Salvia miltiorrhiza, has been widely used to treat cardiovascular diseases. However, its role in modulating ECs under uremic conditions remains incompletely understood. In this research, ECs were exposed to sodium tanshinone IIA sulfonate (STS) and subjected to shear stress and uremic conditions. The results indicate that STS can reduce the suppressive effects on the expression of NF-κB p65, JNK and Collagen I in uremia-induced ECs. Moreover, the downregulation of NF-κB p65, JNK and Collagen I can be enhanced through the inhibition of ERK1/2 and the upregulation of Caveolin-1. These findings suggest that tanshinone IIA may improve EC function under uremic conditions by targeting the Caveolin-1/ERK1/2 pathway, presenting tanshinone IIA as a potential therapeutic agent against AVF immaturity caused by EC dysfunction.
Asunto(s)
Abietanos , Caveolina 1 , Uremia , Uremia/metabolismo , Uremia/tratamiento farmacológico , Uremia/patología , Humanos , Abietanos/farmacología , Abietanos/uso terapéutico , Caveolina 1/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Colágeno Tipo I/metabolismo , Factor de Transcripción ReIA/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , FenantrenosAsunto(s)
Enfermedades Cardiovasculares/etiología , Diabetes Mellitus/fisiopatología , Síndrome Metabólico/complicaciones , Diálisis Peritoneal/efectos adversos , Enfermedades Cardiovasculares/patología , China , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: To investigate the role of wall shear stress in aspects of the formation of fibrin sheath and intimal thickening in a dog model. METHODS: Tunneled silicone 14.5-F catheters were inserted into the left internal jugular vein in eight dogs. The dogs were separated into two groups according to catheter indwelling time of 14 and 28 days. All dogs underwent extracorporeal circulation three times a week. Multidetector computed tomography venography (MDCTV) examination was used to examine the catheter tip thrombus. After the animals were sacrificed, histological and immunohistochemistry evaluations were performed to confirm specific cell populations. We used computer modeling to generate wall shear stress profiles for the blood flow through the catheter. RESULTS: Catheter-related sheaths were identified in all catheter specimens, but there was no fibrin sheath around the catheter tip. There were also differences in wall shear stress between the different venous wall sites. Differences in vein wall thickening at different sites have been found at both 14 days (intima to media (I/M) ratio S1 vs S2: p = 0.01, S3 vs S4: p<0.01) and 28 days (I/M ratio S1 vs S2: p<0.01, S3 vs S4: p<0.05). CONCLUSIONS: After catheter placement, fibrin sheath formation partially covered the catheter. Meanwhile, focal areas of intimal thickening were also seen in the venous wall adjacent to the sites of high wall shear stress. These findings indicate an important role of wall shear stress profiles in fibrin sheath formation and intimal thickening.
