Hypoxia Inducible Factor (HIF) 1-Α dan Vascular Endothelial Growth Factor (VEGF) pada Stroke Iskemik Fase Akut

Lisda Amalia, Ida Parwati, Ahmad Rizal, Ramdan Panigoro, Uni Gamayani, Al Rasyid, Nur Atiik


Stroke iskemik merupakan salah satu penyebab stroke tersering, disebabkan oleh oklusi pembuluh darah serebral dan penyebab kematian ketiga. Saat awitan stroke iskemik terjadi, area otak yang diperdarahi oleh pembuluh darah akan kekurangan oksigen dan nutrisi sehingga sel otak terutama neuron berada dalam risiko, neuron ini masih dapat berfungsi yang dikenal sebagai penumbra. Hipoksik, salah satu karakteristik penumbra merupakan stimulus utama regulasi protein HIF-1α. Hipoksik sendiri merupakan stimulus utama prekondisi iskemik. Prekondisi iskemik akan menghasilkan fenotipe tahan hipoksia yakni protein hypoxia inducible factor (HIF)-1α. HIF-1α merupakan satu-satunya zat yang dikeluarkan oleh jaringan yang mengalami hipoksia. HIF-1α bertindak sebagai protein sinyal yang dapat meregulasi gen protein lain. Efektor HIF-1α antara lain eritropoitin dan vascular endothelial growth factor (VEGF). Pertumbuhan, diferensiasi dan ketahanan sel endotel diregulasi oleh VEGF yang distimulasi dari HIF-1α. Selama iskemik serebral, jaringan yang rusak mencoba untuk meningkatkan pengiriman oksigen melalui induksi angiogenesis melalui produksi VEGF. Hal ini ditandai dengan adanya peningkatan jumlah pembuluh-pembuluh darah mikro di area infark. VEGF dan reseptornya diregulasi oleh HIF-1α dalam hari pertama iskemik.

Hypoxia Inducible Factor (HIF) 1-Α and Vascular Endothelial Growth Factor (VEGF) in Acute Ischemic Stroke


Ischemic stroke is one of the most common causes of stroke, caused by cerebral vascular occlusion and the third cause of death. When the onset of an ischemic stroke occurs, the area of the brain bleeding by blood vessels will lack oxygen and nutrients so that brain cells, especially neurons, are at risk, these neurons can still function known as penumbra. Hypoxic, one of the characteristics of penumbra is the main stimulus for regulation of HIF-1α protein. Hypoxia itself is the main stimulus of ischemic precondition. The ischemic precondition will produce a hypoxic-resistant phenotype namely protein hypoxia inducible factor (HIF) -1α. HIF-1αis the only substance released by tissue that experiences hypoxia. HIF-1α acts as a signaling protein that can regulate other protein genes. Effectors of HIF-1αinclude erythropoitin and vascular endothelial growth factor (VEGF). Growth, differentiation and endurance of endothelial cells are regulated by VEGF stimulated from HIF-1α. During cerebral ischemia, damaged tissue tries to increase oxygen delivery through induction of angiogenesis through VEGF production. This is characterized by an increase in the number of micro blood vessels in the infarct area. VEGF and its receptors are regulated by HIF-1α in the first day of ischemia.


stroke iskemik akut; HIF-1α; luaran klinis; VEGF; acute ischemic stroke; clinical outcome; HIF-1α; VEGF

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Yuwono S. Stroke dan penanganan terkini: Apakah kecatatan permanen atau kematian akibat stroke dapat dicegah?: Kementrian Kesehatan RI; 2016.

Rajamani K, Fisher M. Atherosclerosis-pathogenesis and pathophysiology. Dalam: Ginsberg MD, Bogousslavsky J, eds. Cerebrovascular Disease: Pathophysiology, Diagnosis, and Management, vol.2. Londodn: Blackwell Science;1998:308–18

De Gracia DJ, Rafols JA, Morley SJ, Kayali F. Immunohistochemical mapping of total and phosphorilated eucariotic initiation factor 4 G in rat hippocampus following gobal brain ischemic and reperfusion. Neuroscience. 2006;139;1235–48.

Wang CX, Shuaib A. Critical role of microvasculature basal lamina in ischemic brain injury. Prog Neurobiol.2007;83:140–8.

Takasawa M, Beech JS, Fryer TD, Hong YT, Hughes JL, Igase K, et al. Imaging of Brain Hypoxia in permanent and temporary middle cerebral artery occlusion in the rat using F-18-fluoromisonidazole and positron emission tomography: a pilot study. J Cereb Blood Flow Metab. 2007;27:679–89.

Kane I, Sandercock P, Wardlaw J. Magnetic resonance perfusion diffusion mismatch and thrombolysis in acute ischemic stroke: a systemic review of the evidence to date. J Neurol Neurosurg Psychiatry. 2007:78:485–90.

Baranova O, Miranda LF, Pichiule P, Gragatsis I, Johnson RS, Chaver JC. Neuron specific inactivation of hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci. 2007;27;6320–32.

Lee SH, Kim YJ, Lee KM, Ryu S, Yoon BW. Ischemic preconditioning enhance neurogenesis in subventricular zone. Neuroscience, 2007;146;1020–31.

Sun Y, Jin K, Xie L. VEGF induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003;111;1843–51.

Li Y, Dong H, Chen M, Liu J, Yang L, Chen S et al. Preconditioning repeated hyperbaric oxygen induced myocardial and cerebral protection in patients undergoing coronary artery by pass graft surgery: a prospective, randomized, controllled, clinical trial. J Cardiothorac Vasc Anest, 2011;25;908–16.

Greenberg DA, Jin Kunlin. Vascular endothelial growth factors (VEGF) and stroke. Cell Mol Life Sci.2013;70(10):1753–61.

Ohtaki H, Tajeda T, Dohi K, Yofu S, Nakamachi T, et al. Increased mitochoncrial DNA oxidative damage after transient middle cerebral artery occlusion in mice. Neurosci. Res. 2008;58;349–355.

Landberg M, Lee J, Christensen S, Straka M, De Silva, et al. RAPID automated patient selection for reperfusion therapy; a pooled analysis of the echoplanar imaging thrombolytic evaluation trial (EPITHET) and the dufussion and perfusion imaging evaluation for understanding Stroke evolution (DEFUSE) study. Stroke. 2011;42;1608–14.

Straka M, Albers G, Bammer R. Real time diffusion and perfusion mismatch analysis in acute stroke. J Magn Reson Imaging. 2010;32;1024–37.

Giusti S, Plazas S. Neuroprotection by hypoxic preconditioning involves upregulation of hypoxia-inducible factor 1 alpha in a prenatal model of acute hypoxia. J Neurosci Res. 2011;22766:468–478.

Jeong J, Bae M, Ahn M, Kim S, Sohn T, et al. Regulation and destabilization of HIF-1 alha by ARD1 mediated acetylation. Cell. 2002;111:709–20.

Cheng j, Kang X, Zhang S, Yeh E. SUMO-spesific protease 1 is essential for stabilization of HIF-1alpha during hypoxia. Cell. 2007;131:584–95.

Vertegaal A, Ogg S, Jaffray E, Rodriguez M, Hay R, et al. A proteomic study of SUMO-2 target protein. J Biol Chem.2004;279:22791–33798.

Bruick R. Oxygen sensing in the hypoxic response pathway: regulation of the hypoxia-inducible transcription factor. Genes Dev. 2003;17:2614–23.

Bernaudin M, Nedelec A, Divoux D, Mackenzie E, Petit E, et al. Normobaric hypoxia induceds tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in adult mouse brain. J cereb Blood Flow Metab. 2002;22:393–403.

DOI: https://doi.org/10.24244/jni.v8i3.218


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DOI:  https://doi.org/10.24244/jni 

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