RESUMEN
Hypertension is a disorder controlled by multiple genes and inflammation and vascular remodelling of arteries have been implicated in pathogenesis of this disease. Green tea polyphenols (GrTPs) are rich in antioxidants and are known to inhibit inflammatory responses. A significant time-dependent increase in mRNA expression of both IL-6 and MMP-9 were observed in THP-1 macrophages when cultured in normocholesterolaemic hypertensive sera (P<0.05).
Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Hipertensión/sangre , Interleucina-6/genética , Macrófagos/fisiología , Metaloproteinasa 9 de la Matriz/genética , Fenoles/farmacología , Té , Células Cultivadas , Expresión Génica , Humanos , Extractos Vegetales/farmacología , Polifenoles , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The genomics of atherosclerosis can arise as a result of cross-talk between the genes coding for the LDL-receptor (LDL-R), LXR-alpha, PPARs (alpha, gamma), CD36 and C-myc because these genes control lipid metabolism, cytokine production and cellular activity within the arterial wall. The effect of green tea polyphenols (GTPs) upon such genomics revealed their ability to down-regulate genes coding for PPAR-gamma, CD36, LXR-alpha, C-myc coupled with up-regulation of genes coding for LDL-R and PPAR-alpha at the transcriptional level. Based upon these results, it is proposed that GTPs have the inherent capacity to inhibit the development of atherosclerotic lesions.
Asunto(s)
Arteriosclerosis/genética , Arteriosclerosis/prevención & control , Flavonoides/farmacología , Fenoles/farmacología , Fitoterapia , Té , Proteínas de Unión al ADN , Relación Dosis-Respuesta a Droga , Flavonoides/administración & dosificación , Flavonoides/uso terapéutico , Regulación de la Expresión Génica , Genes myc/genética , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Receptores X del Hígado , Receptores Nucleares Huérfanos , Fenoles/administración & dosificación , Fenoles/uso terapéutico , Polifenoles , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/genética , Receptores de LDL/genética , Factores de Transcripción/genéticaRESUMEN
In sickle cell (SS) vaso-occlusion, the culminating event is blockage of blood vessels by sickled red blood cells (SS RBCs). As shown in animal models, SS RBC-induced vaso-occlusion is often partial, allowing for a residual flow, hence oxygen delivery to partially occluded vessels could reduce vaso-occlusion. The efficacy of an oxygenated perflubron-based fluorocarbon emulsion (PFE) was tested for its anti-vaso-occlusive effects in the ex vivo mesocecum vasculature of the rat. Microvascular obstruction was induced by the infusion of deoxygenated SS RBCs into ex vivo preparations with or without pretreatment with platelet-activating factor (PAF). PAF induced enhanced SS RBC-endothelium interactions, leading to greater vaso-occlusion. Microvascular blockage resulted in increased peripheral resistance units (PRU). Deoxygenated SS RBCs caused a persistent 1.5-fold PRU increase in untreated preparations and approximately a 2-fold PRU increase in PAF-treated preparations. The greater PRU in PAF-treated preparations was caused by widespread adhesion and postcapillary blockage. Oxygenated PFE, but not deoxygenated PFE, resulted in PRU decreases to baseline values in both groups of experiments (with or without PAF). The PRU decrease caused by oxygenated PFE infusion was caused by unsickling of SS RBCs in partially occluded vessels, with no antiadhesive effect on already adherent SS RBCs as assessed by intravital microscopy. PFE had no effect on vascular tone. The efficacy of PFE appears to result from its greater capacity to dissolve oxygen (10-fold higher than plasma). The dislodgement of trapped SS RBCs and an increase in wall shear rates will help reverse the partial obstruction. Thus, oxygenated PFE is capable of reducing SS RBC-induced vaso-occlusion, and further development of this approach is advisable.