| BackgroundIt is well known that morbidity process cf atherosclerosis is very complicated and the nosogenesis is always a investigative hot spot. A large number cf data disclosed that immunity and inflammatory play a important roel during generate and development cf atherosclerosis. Acute Coronary Syndrome(ACS) is a inflammatory with plaque fracture and thrombogenic. Matrix metalloproteinase(MMP-9) can combine with ecto-substantia and degrdn it. Many research consider it as a marker cf plaque fracture. CD40/CD40L pathway penetrates all aspects cf inflammatory and plaque fracture . The interaction cf it generates immune and inflammatory reaction, including adhesion molecule,cytokine and matrix metalloproteinaseone. Thereby, promote thechronic inflammation and acute coronary syndrome. AngiotensinⅡ(AngⅡ) is an important active factor in renin-angiotensin system (RAS). It plays a cruial role in atherosclerosis. It can induce the expression of the MMP-9 and CD40/CD40L . Angiotensin-(1-7) [Ang-(1-7)] is a new member of RAS. It can inhibit the effects induced by AngⅡ, for example, having antihypertensive, antiproliferative and diuresis effects.ObjectivesTo investigate the effects of Ang (1-7) on expression of matrix metalloproteinase (MMP-9) and CD40/CD40L in THP-1 cells which is cultured in vitro,revealing the anti-inflammatory mechanisms of angiotensin(1-7) and identifying the protection of Ang(1-7)Methods1.Culture and inducement of THP-1 cells2.Group: (1) Control group: the THP-1 cells were incubated in 1640 without any stimulators or inhibitors; (2) AngⅡgroup: the THP-1 were stimulated with the final concentration AngⅡ1000nmol/L for 24 hours; (3)-(5)Ang-(1-7) + AngⅡgroup: the THP-1 cells were respectively pretreated with Ang-(1-7) 10nmol/L,100nmol/L, 1000nmol/L for 30min, then added the final concentration AngⅡ1000nmol/L for 24 hours; (6) A-779 + Ang-(1-7) + AngⅡgroup: the THP-1 cells were pretreated with the certain A-779 of 10,000nmol/L for 30min, then added Ang-(1-7) 100nmol/L for 30min, finally stimulated with the final concentration AngⅡ1 000nmol/L for 24 hours; The expression of MMP-9 and CD40/CD40L mRNA was detected by reverse transcriptional (RT-PCR).,the CD40 CD40L expression on the macrophage were detected by flow cytometric analysis . We want to discover the possible mechanism that Ang-(1-7) inhibit the effect of AngⅡon the inflammationResults1. The normal cell growths fine, investigate throught light microscopy, mononuclear cell is floating in 1640; The cell induced by phorbolester 100nmol/L for 48 hours,then, mononuclear cell becomes adherence , the appearance is anomal, stretch out pseudopod.2. Compared with the control group,1000nmol/L AngⅡinduced the expression of the MMP-9 and CD40/CD40L.3.Compared with the AngⅡgroup, the expression of the MMP-9 and CD40/CD40L reduced in the AngⅡ(100nmol/L) plus different concentration of Ang-(1-7) (100nmol/L) group. With the increase in concentration of Ang-(1-7), the expression of the MMP-9 and CD40/CD40L.reduced , the Ang(1-7) inhibitied them concentration dependently.4.The expression of the MMP-9 and CD40/CD40L. was unaffected in the A-779+Ang-(1-7)+AngⅡgroup.The expression of the MMP-9 and CD40/CD40L were similar to control groups.Conclusions1. AngⅡsignificantly induces the expression of the MMP-9 and CD40/CD40L in cultured THP-1 cells2. Ang-(1-7) dose-dependently inhibits the expression of the MMP-9 and CD40/CD40L induced by AngⅡin THP-1 cells3. Ang-(1-7) could anti-inflammatory and stabilize the plaque,the antagonism of Ang(1-7) on the expression of MMP-9 was related to the CD40/CD40L pathway。... |
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