| Background and Objective: The target-organ damage due to hypertension is attributed to two different pathological process: arteriosclerosis and atherosclerosis (AS). As is all known, hypertension is an important risk factor for atherosclerosis, however, the mechanism responsible for the atherosclerotic lesion formation accelerated by hypertension is still unclear. The extension of the lesion is not only related to the force of hemodynamics, but also due to other non-hemodynamic factors. It has been commonly recognized that AS is a chronic inflammatory disease. Monocyte chemoattract protein-1 (MCP-1), a powerful chemotactic factor, has been identified to play an important pathophysiological role in early atherogenesis. Angiotensin II (Ang II), a neurohormonal regulatory factor for arterial blood pressure, has been proved to be able to affect the expression of enormous inflammatory factors such as MCP-1,IL-6 by stimulating endothelia, vascular smooth muscle cells (VSMC) and monocytes. So, Ang II may play an important role in the development of atherosclerotic lesion in hypertension, and it has been conjectured to be the link of hypertension and atherosclerosis. In the present study, we investigated the MCP-1 levels in hypertensive subjects and in aorta of 2K1C hypertensive rats, and the effect of Ang II on the expression of MCP-1 in human umbilical vein endothelial cells (HUVECs).Methods: Three parts were performed sequentially: (1) the fasting serum levels of MCP-1 and Ang II were measured in 32IVhypertensive and 30 healthy subjects by ELISA and radio-immunoassay respectively. (2) 41 rats including normotensive and 2K1C hypertensive rats were divided into 5 groups: negative control group, positive central groups of 7 days> 14 days^ 28 days and treatment group. The expression of MCP-lmRNA in rat aorta was detected by RT-PCR and in situ hybridization respectively. The levels of Ang II in serum and in aorta were measured by radioimmunoassay. (3) The effects of Ang II of different concentrations and stages on the expression of MCP-1 were performed in HUVECs; The MCP-1 protein in supernatant was assayed by ELISA, and MCP-lmRNA expression was detected by RT-PCR.Results: (1) The concentration of MCP-1 in hypertensions were significantly higher than that of normotensives (18.66?.55 Vs 15.45?.13,P<0.001), but the concentration of Ang II had no significant difference between the two groups (32.98?4.61 Vs 32.51?0.65, P=0.887); and no correlation was found between MCP-1 and Ang II or MCP-1 and blood pressure (R=0.013,-0.082,-0.011 respectively,P>0.05); (2) No expression of MCP-lmRNA was detected by RT-PCR and in situ hybridization in aorta of normotensive rats; after 7 days, The expression of MCP-lmRNA was detected in aorta of 2K1C rats ^specially in intima , and it significantly increased with a duration-dependent mode, with a peak at 28 days. After treatment with losartan (25mg/kg/d) for 28 days, the expression of MCP-lmRNA decreased significantly compared with nontreatment groups(MCP-l/GAPDH ratio: 0, 0.58?.10> 1.14?.09> 1.52?.20 > 0.66?.07 respective, PO.01). (3) A little expression MCP-lmRNA in HUVECs was detected without existence of Ang II, however, Ang II dramatically activated the expression of MCP-lmRNA.after preincubation for 6 hours at a dose-dependent manner. The strongest expression of MCP-lmRNA was at the dose of lxlO~7mol/l (MCP-1/GAPDHratio: 0.40?.08> 0.95?.2K 1.16?.13> 1.48?.24> 1.01?.18 respective). (4)with incubation of HUVECs with Ang II for 2 hours, the expression of MCP-lmRNA was markedly increased, and the strongest expression was found at the fourth hour, but almost recovered to basal level at the 24th hour(MCP-l/GAPDH ratio: 0. 3?.08> 0.99?.2K 1.19?.30> 1.03?.18> 0.8?.15 and 0.34?.07 respective).(5)The concentration of MCP-1 in supernatant of HUVECs increased gradually after 12 and 24 hours when HUVECs were stimulated by Ang II (20.24?.36 Vs 25.26?.28, PO.001), (6) Losartan had no effect on the expression of MCP-1 in HUVECs. But the effect o...
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