Efek Pemberian Matrix Metalloproteinase-9 ( MMP- 9) Rna Interference Terhadap Ekspresi MMP- 9 Pada Kultur Sel Endotel Vaskular

Abstract

Retinal neovascularization is the main problem that causes blindness in many types of eye desease. Neovascularization occurs in ischemic retina, and several important mediators that induce neovascularization is secreted by the surrounding cell and endothelial cell vessels. Matrix metalloproteinase-9 is an enzyme secreted by endothelial cell vessels and plays an important role in the pathogenesis of retinal induce neovascularization. Vascular endothelial cells were cultured and transfected with Matrix Metalloproteinase -9 RNA interference in two doses (100nM or 200nM) and the cells were taken at 24, 48 and 72 hours. The expression of Matrix Metalloproteinase -9 protein levels were examined by immunocytochemistry, and compared with control group. The data were analyzed with factorial anova. Statistical analysis showed that transfection with different doses of MMP-9 RNAi gave a significant different effect on MMP-9 expression (pvalue < 0.05), while exposure time did not give significant difference (p-value < 0.05). This in-vitro study indicated that transfection of MMP-9 RNAi with dose 200nM reduced the expression of MMP-9 by 50% compared to the control. Because exposure time was not significant, the lowest expression of MMP-9 can be achieved by transfecting MMP-9 RNAi 200nM for 24 hours. This is the first study that demonstrates the effectiveness of RNA interference mediated targeting of MMP-9 to reduce the MMP-9 expression in vascular endothelial cell lines Key Words : Matrix Metalloproteinase -9 -RNA interference -vascular endothelial cell lines. PENDAHULUANAngiogenesis merupakan suatu proses terbentuknya pembuluh darah baru dari endotel vaskular. Proses angiogenesis sangat penting dalam reproduksi, pertumbuhan dan proses penyembuhan luka. Pada proses tersebut angiogenesis terkontrol dengan baik dimana proses pembentukan pembuluh darah baru akan berlangsung dalam beberapa waktu dan pada saat tertentu prosesnya akan berhenti. Ada beberapa penyakit yang mengakibatkan proses angiogenesis menjadi tidak terkontrol sama sekali. Retinopati diabetika proliferatif, degenerasi makula terkait usia tipe eksudatif, oklusi vena retina sentral dan retinopathy of prematurity seringkali mengakibatkan proses angiogenesis yang tidak terkontrol, hal ini akan mengakibatkan munculnya pembuluh darah baru pada retina dan selanjutnya bisa mengakibatkan kebutaaan. Proses angiogenesis terdiri dari beberapa mekanisme yaitu peningkatan angiogenic growth factor, degradasi matriks ekstra sel, migrasi dan proliferasi sel endotel, pembentukan komponen matriks ekstra sel baru dan diikuti dengan pembentukan pipa kapiler baru.Degradasi matriks ekstra sel atau proteolisis merupakan proses penting dalam pembentukan neovaskularisasi sehingga terjadi kerusakan pertahanan anatomi dari pembuluh darah. Pada tahap ini dibutuhkan peranan matrix metalloproteinases (MMPs). Matrix metalloproteinase-9 adalah anggota MMPs kelompok gelatinase yang memiliki keistimewaan yaitu dapat memecah kolagen tipe IV. Kolagen tipe IV sendiri harus dipecah untuk memfa...

Activity of robusta coffee on the expression of CRP and MMP-9 against hyperlipidemia

“…This happens since the control group is the only one that is given a standard diet so that LDL does not occur in the intima tunica. In general, under normal conditions MMP-9 is also secreted to normal limit but if there is inflammation there will be an increase in MMP-9 (Wulandari et al, 2016).…”