Induction and functional significance of the heme oxygenase system in pathological shear stress in vivo

The present study examined the heme oxygenase (HO) system in an in vivo murine model of pathological shear stress induced by partial carotid artery ligation. In this model, along with upregulation of vasculopathic genes, HO-1 is induced in the endothelium and adventitia, whereas HO-2 is mainly upregulated in the endothelium. Within minutes of ligation, NF-κB, a transcription factor that upregulates vasculopathic genes and HO-1, is activated. Failure to express either HO-1 or HO-2 exaggerates the reduction in carotid blood flow and exacerbates vascular injury. After artery ligation, comparable induction of HO-2 occurred in HO-1+/+and HO-1−/−mice, whereas HO-1 induction was exaggerated in HO-2−/−mice compared with HO-2+/+mice. Upregulation of HO-1 by an adeno-associated viral vector increased vascular HO-1 expression and HO activity and augmented blood flow in both ligated and contralateral carotid arteries. Acute inhibition of HO activity decreased flow in the ligated carotid artery, whereas a product of HO, carbon monoxide (CO), delivered by CO-releasing molecule-3, increased carotid blood flow. In conclusion, in the partial carotid artery ligation model of pathological shear stress, this study provides the first demonstration of 1) upregulation and vasoprotective effects of HO-1 and HO-2 and the vasorelaxant effects of CO as well as 2) vascular upregulation of HO-1 in vivo by an adeno-associated viral vector that is attended by a salutary vascular response. Induction of HO-1 may reside in NF-κB activation, and, along with induced HO-2, such upregulation of HO-1 provides a countervailing vasoprotective response in pathological shear stress in vivo.

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Ekspresi PDGF-B dan SCUBE 1 pada Arteri Karotis Mencit yang Diligasi dan Tidak Diligasi

Jurnal Kesehatan Andalas ◽

10.25077/jka.v4i2.275 ◽

2015 ◽

Vol 4 (2) ◽

Author(s):

Ranti Verdiana ◽

Hirowati Ali ◽

Husnil Kadri

Keyword(s):

Shear Stress ◽

Carotid Artery ◽

Carotid Arteries ◽

Hypothesis Test ◽

Intimal Thickening ◽

Artery Ligation ◽

Adaptive Process ◽

Carotid Artery Ligation ◽

Significant Difference ◽

Diffuse Intimal Thickening

AbstrakDiffuse Intimal Thickening (DIT)terjadi sebagai adaptasi fisologis terhadap shear stress yang dapat terbentuk melalui ligasi arteri karotis. Ligasi akan menyebabkan terbentuknya penebalan tunika intima pada pembuluh darah. Penebalan tunika intima terjadi melalui proses inflamasi yang melibatkan sitokin seperti PDGF-Bdan SCUBE 1 yang terdapat di dalam trombosit dan endotel. Tujuan penelitian adalah mengetahui ekspresi PDGF-B dan SCUBE 1 pada arteri karotis mencit yang diligasi dan tidak diligasi. Desain penelitian adalah eksperimental dengan menggunakan 5 ekor mencit yang dilakukan ligasi pada arteri karotis kiri sedangkan arteri karotis kanan tidak diligasi. Kemudian, arteri karotis tersebut dikumpulkan dan diperiksa kadar PDGF-B dan SCUBE 1 dengan menggunakan PCR. Uji hipotesis yang digunakan adalah independent t-test. Hasil penelitian adalah tidak terdapat perbedaan bermakna PDGF-B pada arteri karotis mencit yang diligasi dan tidak diligasi (p = 0,66; p>0,05) dan tidak terdapat perbedaan bermakna SCUBE 1 pada arteri karotis mencit yang diligasi dan tidak diligasi (p = 0,33; p>0,05).Kata kunci: diffuse intimal thickening, DIT, PDGF-B, SCUBE 1, PCR. AbstractDiffuse Intimal Thickening (DIT) develops as physiological adaptive process of shear stress which can be performed by carotid artery ligation in mice. Ligation will cause an intimal thickening in vessel. Intimal thickening occurs through an inflammatory process that involves cytokines such as PDGF-B and SCUBE 1 that are found in platelet and endothelial cells.The objective of this study was to determine the expression of PDGF-B and SCUBE 1 in ligated and non ligated carotid artery of mice.The design study was experimental. This study used 5 mouse that were ligated in left carotid artery and non ligated in right carotid artery. Then, those carotid arteries were collected and examined PDGF-B and SCUBE 1 levels using PCR. The hypothesis test of this study was Independent t-test.The result was no significant difference between PDGF-B in ligated and non ligated carotid artery of mice (p = 0.66; p>0.05). The same result was also found in SCUBE 1 as well (p = 0.33; p>0.05).Keywords: diffuse intimal thickening, DIT, PDGF-B, SCUBE 1, PCR.

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