کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8769012 | 1597918 | 2018 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Peripheral vascular atherosclerosis in a novel PCSK9 gain-of-function mutant Ossabaw miniature pig model
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کلمات کلیدی
RBFMDCTMPRHDL-CGFRVLDL-CLDL-CMREPCSK9ROIBold-MRIGOFCTAIVUS - IvuaComputed tomography angiography - آنژیوگرافی توموگرافیک کامپیوتریMagnetic resonance elastography - انعطاف پذیری رزونانس مغناطیسیGain of function - به دست آوردن عملکردterminal deoxynucleotidyl transferase dUTP nick-end labeling - ترمینال deoxynucleotidyl transferase dUTP نهایی پایان برچسبMultidetector computed tomography - توموگرافی کامپیوتری MultidetectorTUNEL - تونلrenal blood flow - جریان خون کلیویdihydroethidium - دی هیدروتیدیمAtherogenic diet - رژیم غذایی خامnormal diet - رژیم معمولیintravascular ultrasound - سونوگرافی داخل عضلانیmean arterial pressure - فشار متوسط شریانیhigh-density lipoprotein cholesterol - لیپوپروتئین پرچگالی یا اچدیالregion of interest - منطقه مورد نظرGlomerular filtration rate - نرخ فیلتراسیون گلومرولیmap - نقشهwild-type - نوع وحشیDHE - وLow-density lipoprotein cholesterol - کلسترول لیپوپروتئین با چگالی کمVery low-density lipoprotein cholesterol - کلسترول لیپوپروتئین با چگالی کم
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Peripheral vascular atherosclerosis in a novel PCSK9 gain-of-function mutant Ossabaw miniature pig model Peripheral vascular atherosclerosis in a novel PCSK9 gain-of-function mutant Ossabaw miniature pig model](/preview/png/8769012.png)
چکیده انگلیسی
Hypercholesterolemia is a major risk factor for atherosclerosis. Remaining challenges in the management of atherosclerosis necessitate development of animal models that mimic human pathophysiology. We characterized a novel mutant pig model with DNA transposition of D374Y gain-of-function (GOF) cDNA of chimp proprotein convertase subtilisin/kexin type-9 (PCSK9), and tested the hypothesis that it would develop peripheral vascular remodeling and target organ injury in the kidney. Wild-type or PCSK9-GOF Ossabaw miniature pigs fed a standard or atherogenic diet (AD) (nâ=â7 each) were studied in vivo after 3 and 6 months of diet. Single-kidney hemodynamics and function were studied using multidetector computed tomography and kidney oxygenation by blood oxygen level-dependent magnetic resonance imaging. The renal artery was evaluated by intravascular ultrasound, aortic stiffness by multidetector computed tomography, and kidney stiffness by magnetic resonance elastography. Subsequent ex vivo studies included the renal artery endothelial function and morphology of abdominal aorta, renal, and femoral arteries by histology. Compared with wild type, PCSK9-GOF pigs had elevated cholesterol, triglyceride, and blood pressure levels at 3 and 6 months. Kidney stiffness increased in GOF groups, but aortic stiffness only in GOF-AD. Hypoxia, intrarenal fat deposition, oxidative stress, and fibrosis were observed in both GOF groups, whereas kidney function remained unchanged. Peripheral arteries in GOF groups showed medial thickening and development of atheromatous plaques. Renal endothelial function was impaired only in GOF-AD. Therefore, the PCSK9-GOF mutation induces rapid development of atherosclerosis in peripheral vessels of Ossabaw pigs, which is exacerbated by a high-cholesterol diet. This model may be useful for preclinical studies of atherosclerosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 192, February 2018, Pages 30-45
Journal: Translational Research - Volume 192, February 2018, Pages 30-45
نویسندگان
Ahmad F. Hedayat, Kyoung-Ha Park, Taek-Geun Kwon, John R. Woollard, Kai Jiang, Daniel F. Carlson, Amir Lerman, Lilach O. Lerman,