Increased atherosclerosis in diabetic dyslipidemic swine

Dixon, John R.; Shen, Siming; Vuchetich, James P.; Wysocka, Elżbieta; Sun, Grace Y.; Sturek, Michael

doi:10.1194/jlr.m200134-jlr200

Cited by 44 publications

(10 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, just like in the current study, cholesterol serum concentrations were slightly higher in the statin-treated group, which, nevertheless, experienced improvement in microvascular vasoreactivity [47]. In diabetic dyslipidemic male Yucatan pigs, daily administration of 80 mg of atorvastatin reduced triglyceride but not LDL levels and still decreased vascular collagen deposition [48]. On the contrary, in familial hypercholesterolemic pigs, simvastatin did not reduce triglyceride but decreased LDL levels and the largest effect was noted at a daily dose of 200 mg [49].…”

Section: Discussionmentioning

confidence: 57%

Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

et al. 2011

View full text Add to dashboard Cite

Objective: Isolated diastolic dysfunction is present in 40% of heart failure patients. It has been attributed to myocardial fibrosis and related to cardiovascular risk factor exposure. We hypothesized that simvastatin will improve these dynamics in experimental hypercholesterolemia (HC). Methods: Three groups of pigs were studied after 12 weeks of normal (N) diet, HC diet, or HC diet with simvastatin (80 mg/day) treatment. Cardiac function was assessed by electron beam computed tomography (EBCT) and percentage of myocardium occupied by microvessels (myocardial vascular fraction) was calculated by micro-CT. Collagen content was determined by Sirius red staining and confirmed by a quantitative, hydroxyoproline-based assay. Results: Compared with N, LDL serum concentration was higher in HC and HC + simvastatin (1.0 ± 0.1 vs. 7.9 ± 1.7 and 9.6 ± 1.2 mmol/L, p < 0.05 for both). Cardiac early diastolic filling was reduced in HC compared with N (102.4 ± 11.3 vs. 151.1 ± 12.1 mL/s; p < 0.05) but restored in HC + simvastatin (176.8 ± 21.3 mL/s, p < 0.05 vs. HC). Compared with N, myocardial vascular fraction was higher in HC but not in HC + simvastatin (1.98 ± 0.84 vs. 4.48 ± 0.31 and 2.95 ± 0.95%; p < 0.05 for HC vs. N). Myocardial collagen content was higher in HC than in HC + simvastatin and N (4.72 ± 1.03 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p < 0.05 for HC vs. N), which was attributable mainly to an increase in collagen III (2.90 ± 0.48 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p < 0.05 for HC vs. N). Conclusions: Simvastatin is able to prevent diastolic dysfunction in experimental HC independent of its lipid lowering effect. This beneficial effect is, at least partially, due to a decrease in myocardial fibrosis and angiogenesis.

show abstract

Section: Discussionmentioning

confidence: 57%

Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Yucatan miniature pigs fed a high fat diet and treated with Alloxan develop hypercholesterolaemia and insulin resistance 242 . When compared to high fat fed untreated pigs, the high fat fed Alloxan-treated group showed significantly increased coronary atherosclerosis 243 . Similarly, Alloxan treatment in conjunction with high fat feeding increased atherosclerosis in Sinclair miniature pigs 76 .…”

Section: Diabetes Mellitus Accelerated Atherosclerosismentioning

confidence: 83%

Large animal models of cardiovascular disease

Tsang

Rashdan

Whitelaw

et al. 2016

Cell Biochemistry & Function

113

View full text Add to dashboard Cite

The human cardiovascular system is a complex arrangement of specialized structures with distinct functions. The molecular landscape, including the genome, transcriptome and proteome, is pivotal to the biological complexity of both normal and abnormal mammalian processes. Despite our advancing knowledge and understanding of cardiovascular disease (CVD) through the principal use of rodent models, this continues to be an increasing issue in today's world. For instance, as the ageing population increases, so does the incidence of heart valve dysfunction. This may be because of changes in molecular composition and structure of the extracellular matrix, or from the pathological process of vascular calcification in which bone‐formation related factors cause ectopic mineralization. However, significant differences between mice and men exist in terms of cardiovascular anatomy, physiology and pathology. In contrast, large animal models can show considerably greater similarity to humans. Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research. These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo. In turn, this will help bridge the gap between basic science and clinical applications by facilitating the refinement of therapies for cardiovascular disease. 2016 The Authors. Published by John Wiley & Sons Ltd.

show abstract

“…[1] Also the incidence of atherosclerosis is 3 – 4 times greater in diabetics than non-diabetics at comparable plasma total cholesterol concentrations. [2] Accordingly, prevention of onset and progression of atherosclerosis, as well as tight glycemic control are essential goals of treatment in type two diabetic patients. It has been extensively demonstrated that inflammation plays a central role in atherogenesis, and mediates all stages of this disease, from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits

Hadi

Al-Amran

Hussein

et al. 2012

Journal of Cardiovascular Disease Research

View full text Add to dashboard Cite

Background:Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance.Objectives:The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways.Materials and Methods:Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin – 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness.Results:Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05).Conclusions:Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters.

show abstract

Increased atherosclerosis in diabetic dyslipidemic swine

Cited by 44 publications

References 65 publications

Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

Large animal models of cardiovascular disease

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits

Contact Info

Product

Resources

About