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Pharmacology

Dyslipidemia and Atherosclerosis

2016-11-28
15759
Kunming, China, November 28, 2016

The aged cynomolgus macaque has been a well-studied translational model for human atherosclerosis, hypercholesterolemia and essential hypertension.   Cynomolgus macaques share several similarities in lipoproteins and the cardiovascular system with humans. While cynomolgus macaques do develop atherosclerotic lesions spontaneously, the process is markedly exacerbated when a cholesterol-containing diet is fed.  Macaques fed with diets similar in fat and cholesterol content to those commonly consumed by people in industrialized nations develop dyslipidemia/ hyperlipoproteinemia and atherosclerosis with many similarities to atherosclerosis of human beings.  The progression of atherosclerosis in the macaque also resembles that of humans as lesions develop initially in the aorta, subsequently affecting the coronary arteries, the common carotid arteries, and ultimately, the cerebral arteries.  Similar to man, the atherogenic lesion progress from the development of fatty streaks to atheromatous plaques with lesion complications such as calcification, ulceration, haemorrhage, stenosis and thrombosis.  The importance of the macaque as translational models is reflected not only in their resemblance to humans in the development of dyslipidemia and atherosclerosis, but also because they display close variants of the comorbidities (e.g. obesity and diabetes) that often accompany atherosclerosis and coronary arterial disease (CAD).


KBI has incomparably large cohorts of macaques with spontaneous metabolic disorders making it possible to screen and select dyslipidemic/ hyperlipoproteinemia models from the colony. Furthermore, HFD (High Fat Diet) induced hyperlipidemia models are also available to conduct efficacy, PK/PD, biomarkers, and possible adverse effects studies.


     

    


For research aimed at clinical translation, it is imperative that initial results from rodent studies be confirmed in a large animal model more closely resembling the heart of humans. KBI utilizes Cardiac Magnetic Resonance Imaging (CMRI) based on available NHP protocols and back-translated human protocols to get quantitative information on:
·  Lumen and vessel wall thickness
·  Plaque burden and inflammation


Abdominal Aorta and Iliac Arteries

Abdominal Aorta

  

Iliac Arteries

  

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