RESUMO
Endothelial dysfunction is thought to be a major cause of vascular injury in smokers. Ghrelin is a recently discovered peptide that plays a modulatory role in atherosclerosis. However, it is unknown how ghrelin regulates nicotine-induced vascular cell adhesion molecule-1 (VCAM-1) expression. We examined nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells pretreated with ghrelin and detected the activity of protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor (NF)-kappaB. Our study showed that ghrelin inhibited nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells in a concentration-dependent and time-dependent way. We also found that ghrelin inhibited nicotine-induced PKC, p38 MAPK, and NF-kappaB activation. The results suggest that ghrelin inhibits nicotine-induced VCAM-1 expression, and PKC, p38 MAPK, and NF-kappaB play active roles in that process. Exogenous ghrelin may provide a possible approach for preventing or reversing atherosclerosis in smokers.
Assuntos
Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Grelina/farmacologia , Nicotina/efeitos adversos , Molécula 1 de Adesão de Célula Vascular/biossíntese , Aterosclerose/prevenção & controle , Western Blotting , Linhagem Celular , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Grelina/uso terapêutico , Humanos , NF-kappa B/metabolismo , Proteína Quinase C/metabolismo , Veias Umbilicais/citologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: During the last several years the role of adipose tissue in contributing to obesity-associated cardiovascular and metabolic risk has gained much attention. AIM: To examine the expression of TNF-alpha protein in omental and subcutaneous adipose tissue in correlation with plasma PAI-1 and other clinical parameters in obesity subjects. MATERIAL AND METHODS: Paired biopsies of omental and subcutaneous fat were collected during surgery in 32 obesity subjects. The expression of TNF-alpha protein in omental and subcutaneous fat was quantified by using Western blot method, and correlations with plasma PAI-1, homeostasis model assessment insulin resistance (HOMA-IR) and lipid were investigated. RESULTS: TNF-alpha protein expression was higher in omental than in subcutaneous adipose tissue (P<0.01). Significant positive linear correlations were found between TNF-alpha protein in omental adipose tissue and plasma PAI-1 in obesity subjects. TNF-alpha protein in omental fat was positively associated with HOMA-IR, triglycerides and negatively with HDL-cholesterol. CONCLUSION: TNF-alpha expression in omental adipose tissue could play a key role in contributing to cardiovascular risk in central obesity subjects.
