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2015 ; 13
(ä): 312
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English Wikipedia
Göttingen minipig model of diet-induced atherosclerosis: influence of mild
streptozotocin-induced diabetes on lesion severity and markers of inflammation
evaluated in obese, obese and diabetic, and lean control animals
#MMPMID26394837
J Transl Med
2015[Sep]; 13
(ä): 312
PMID26394837
show ga
BACKGROUND: From a pharmacological perspective, readily-available,
well-characterized animal models of cardiovascular disease, including relevant in
vivo markers of atherosclerosis are important for evaluation of novel drug
candidates. Furthermore, considering the impact of diabetes mellitus on
atherosclerosis in human patients, inclusion of this disease aspect in the
characterization of a such model, is highly relevant. The objective of this study
was to evaluate the effect of mild streptozotocin-induced diabetes on ex- and in
vivo end-points in a diet-induced atherosclerotic minipig model. METHODS:
Castrated male Göttingen minipigs were fed standard chow (CD), atherogenic diet
alone (HFD) or with superimposed mild streptozotocin-induced diabetes (HFD-D).
Circulating markers of inflammation (C-reactive protein (CRP), oxidized
low-density lipoprotein (oxLDL), plasminogen activator inhibitor-1, lipid and
glucose metabolism were evaluated together with coronary and aortic
atherosclerosis after 22 or 43 diet-weeks. Group differences were evaluated by
analysis of variance for parametric data and Kruskal-Wallis test for
non-parametric data. For qualitative assessments, Fisher's exact test was
applied. For all analyses, p < 0.05 was considered statistically significant.
RESULTS: Overall, HFD and HFD-D displayed increased CRP, oxLDL and lipid
parameters compared to CD at both time points. HFD-D displayed impaired glucose
metabolism as compared to HFD and CD. Advanced atherosclerotic lesions were
observed in both coronary arteries and aorta of HFD and HFD-D, with more advanced
plaque findings in the aorta but without differences in lesion severity or
distribution between HFD and HFD-D. Statistically, triglyceride was positively (p
= 0.0039), and high-density lipoprotein negatively (p = 0.0461) associated with
aortic plaque area. CONCLUSIONS: In this model, advanced coronary and aortic
atherosclerosis was observed, with increased levels of inflammatory markers,
clinically relevant to atherosclerosis. No effect of mild streptozotocin-induced
diabetes was observed on plaque area, lesion severity or inflammatory markers.