Caffeic Acid Phenethyl Ester Menurunkan Ekspresi Endoglin pada Kultur HUVECs yang Dipapar Glukosa Tinggi
DOI:
https://doi.org/10.21776/ub.jkb.2013.027.04.3Abstract
Komplikasi vaskuler pada diabetes mellitus (DM) menimbulkan keadaan hipoksia yang berlanjut pada proses angiogenesis yang dapat dicegah dengan antiioksidan diantaranya caffeic acid phenethyl Ester (CAPE). Penelitian ini bertujuan untuk mengetahui efek pemberian CAPE terhadap ekspresi endoglin pada HUVECs yang dipapar glukosa tinggi. Penelitian ini menggunakan desain analitik eksperimental pada HUVECs primer yang dipapar glukosa tinggi. HUVECs dibagi menjadi 5 kelompok yaitu: 1. HUVECs+DMSO (kontrol negatif), 2. HUVECs+glukosa 22 mM+DMSO (kontrol positif), 3. HUVECs+glukosa 22 mM+CAPE 3 µM+DMSO 4. HUVECs+glukosa 22 mM+CAPE 10 µM+DMSO, 5. HUVECs+glukosa 22 mM+CAPE 30 µM+DMSO. Inkubasi dilakukan selama 48 jam pada suhu 37°C, lalu dilakukan pengecatan imunositokimia menggunakan antibodi endoglin. Ekspresi endoglin diamati dengan mikroskop cahaya 400x, endoglin tervisualisasi berwarna coklat. Didapatkan perbedaan efek CAPE di antara kelompok perlakuan terhadap ekspresi endoglin pada HUVECs yang dipapar glukosa tinggi (ANOVA p=0,000). Ekspresi endoglin pada tiap kelompok didapatkan perbedaan signifikan (Tukey test, p<0,05), kecuali antar kelompok 1 dan 5 tidak didapatkan perbedaan signifikan (Tukey test, p>0,05). Dengan Person test didapatkan korelasi positif signifikan antara pemberian CAPE dengan ekspresi endoglin pada HUVECs yang dipapar glukosa tinggi (r=-0,839; p=0,000). Pemberian CAPE dapat menurunkan ekspresi endoglin pada HUVECs yang dipapar glukosa tinggi.Kata Kunci: Caffeic acid phenetyl ester, endoglin, HUVECs
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Perkumpulan Endokrinologi Indonesia. Konsensus Pengelolaan Diabetes Mellitus Tipe 2 di Indonesia. Jakarta: PERKENI; 2003.
Apushkin M, Scott L, and Lyon A. Screening for Spesific Disease. Clinical Pathways in Vitreoretina Disease. New York: Thieme Medical Publishers Inc.; 2003: p. 374-377.
DaSilva Z, Freitas AM, and Marcon IM. Risk Factors Related to Severity of Diabetic Retinopathy. Arquivos Brasileiros de Oftalmologia. 2003; 66: 739-743.
Stehouwer CD, Lambert J, Donker AJ, and Van Hinsbergh VW. Endothelial Dysfunction and Pathogenesis of Diabetic Angiopathy. Cardiovascular Research. 1997; 34(1): 55-68.
Cai J and Boulton M. The Pathogenesis of Diabetic Retinopathy: Old Concepts and New Questions. Eye. 2002; 16: 242-260.
Cines DB, Pollak ES, Buck CA, et al. Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders. Blood. 1998; 91: 3527-3561.
Catrina S, Okamoto K, Pereira T, Brismar K, and Poellinger L. Hyperglycemia Regulates Hypoxia-Inducible Factor 1-α Protein Stability and Function. Diabetes. 2004; 53(12): 3226-3232.
Michiels C, Arnould T, and Remacle J. Endothelial Cell Responses to Hypoxia: Initiation of Cascade of Cellular Interactions. Biochimica et Biophysica Acta. 2000; 1497(1): 1-10.
Orević G, Matušan-Ilijaš K, Babarović E, et al. Hypoxia Inducible Factor-1α Correlates with Vascular Endothelial Growth Factor A and C Indicating Worse Prognosis in Clear Cell Renal Cell Carcinoma. Journal of Experimental and Clinical Cancer Research. 2009; 28: 40.
Tailor A and Granger D. Role of Adhesion Molecules in Vascular Regulation and Damage. Current Hypertension Reports. 2000; 2: 78-83.
Li C, Issa R, Kumar P, et al. CD105 Prevents Apoptosis in Hypoxic Endothelial Cells. Journal of Cell Science. 2003; 116: 2677-2685.
Felmeden D, Blann A, and Lip G. Angiogenesis: Basic Pathophysiology and Implication for Disease. European Heart Journal. 2003; 24: 586-603.
Pepper M. Manipulating Angiogenesis from Basic Science to Bedside. Atherosclerosis, Thrombosis, and Vascular Biology. 1997; 17: 605-619.
Fonsatti E, Nicolay HJM, Altomonte M, Covre A, and Maio M. Targeting Cancer Vasculature Via Endoglin/CD105: A Novel Antibody-Based Diagnostic and Therapeutic Strategy in Solid Tumours. Cardiovascular Research. 2010; 86: 12-19.
Wikstrom P, Lissbrant I, Stattin P, Egevad L, and Bergh A. Endoglin (CD105) is Expressed on Immature Blood Vessels and is a Marker for Survival in Prostate Cancer. The Prostate. 2002; 51: 268-275.
Wong S, Hamel L, Chevalier S, and Philip A. Endoglin Expression on Human Microvascular Endothelial Cells Association with Betaglycan and Formation of Higher Order Complexes with TGF-beta Signalling Receptors. European Journal of Biochemistry. 2000; 267: 5550-5560.
Ten Dijke P, Goumans M, and Pardali E. Endoglin in Angiogenesis and Vascular Diseases. Angiogenesis. 2008; 11: 79-89.
Sanchez-Elsner T, Botella LM, Velasco B, Langa C, and Bernabeu C. Endoglin Expression is Regulated by Transcriptional Cooperation Between Hypoxia and Transforming Growth Factor-b Pathways. Journal of Biological Chemistry. 2002; 277: 43799-43808.
Cicala C, Morello S, Iorio C, Capasso R, Borrelli F, and Mascolo N. Vascular Effects of Caffeic Acid Phenethyl Ester (CAPE) on Isolated Rat Thoracic Aorta. Life Sciences. 2003; 73: 73-80.
Natarajan K, Singh S, Burke T, Grunberger D, and Aggarwal B. Caffeic Acid Phenethyl Ester is a Potent Specific Inhibitor of Activation of Nuclear Transcription Factor NF-kB. Immunology. 1996; 93: 9090-9095.
Ushio-Fukai M, Tang Y, Fukai T, et al. Novel Role of gp91 (phox)-containing NAD(P)H Oxidase in Vascular Endothelial Growth Factor-Induced Signaling and Angiogenesis. Circulation Research. 2002; 91(12): 1160-1167.
Durmuş M, Yilmaz HR, Uz E, and Özçelik N. The Effect of Caffeic Acid Phenethyl Ester (CAPE) Treatment on Levels of MDA, NO and Antioxidant Enzyme Activities in Retinas of Streptozotocin-Induced Diabetic Rats. Turkish Journal of Medical Sciences. 2008; 38(6): 525-530.
Izuta H, Simizawa M, Tsuruma K, Araki Y, Mishima S, and Hara H. Bee Products Prevent VEGF-Induced Angiogenesis in Human Umbilical Vein Endothelial Cells. Biomed Complementary and Alternative Medicine. 2009; 9: 45.
Torsney B, Charlton R, Parums D, Collin M, and Arthur H. Inducible Expression of Human Endoglin During Inflammation and Wound Healing. Inflammation Research. 2002; 51(9): 464-470.
Schalkwijk CG and Stehouwer CDA. Vascular Complications in Diabetes Mellitus: the Role of Endothelial Dysfunction. Clinical Science. 2005; 109: 143-159.
Treins C, Giorgetti-Peraldi S, Murdaca J, and Van Obberghen E. Regulation of Vascular Endothelial Growth Factor Expression by Advanced Glycation End Products. The Journal of Biological Chemistry. 2001; 276: 43836-43841.
Kian AYS and Mustafa S. Influence of Enriched Live Prey and Other Artificial Diets on RNA and DNA Concentration in the Ovary of Tiger Prawn, Penaeus monodon. Journal of Applied Aquaculture. 2005; 16: 147-153.
Sud'ina G, Mirzoeva O, Pushkareva G, et al. Caffeic Acid Phenethyl Ester as a Lipoxygenase Inhibitor with Antioxidant Properties. Federation of the Societies of Biochemistry and Molecular Biology Letters. 1993; 329: 21-24.
Iraz M, Fadıllıoğlu E, Taşdemir S, Ateş B, and Erdoğan S. Dose Dependent Effects of Caffeic Acid Phenethyl Ester on Heart Rate and Blood Pressure in Rats. European Journal of General Medicine. 2005; 2(2): 69-75
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