Pathobiochemistry of combined diabetes and atherosclerosis studied on a novel animal model

The hyperlipemic-hyperglycemic hamster

Maya Simionescu, Doina Popov, Anca Sima, Mirela Hasu, Gabriela Costache, Silviu Faitar, Alexandra Vulpanovici, Camelia Stancu, David Stern, Nicolae Simionescu

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Because accelerated atherosclerosis is the main complication of diabetes, we devised, a new animal model that combines these two diseases, and investigated their joint impact on the main plasma components and organs known to be most affected in each disorder. Male Golden Syrian hamsters were subjected to three experimental conditions: streptozotocin-induced diabetes (D), diet-induced hyperlipemia (H), and a combination of hyperlipemia and diabetes (HD). At time intervals ranging from 2 to 24 weeks, the animals were sacrificed, the appropriate plasma constituents were determined, and the ultrastructural modifications of relevant tissues such as the heart, cardiac valves, coronary arteries, aorta, retina, and kidney were examined. The HD hamsters were characterized by marked alterations of plasma components, ie, increase in circulating glucose, cholesterol and lipid peroxide levels, glycation of albumin, and the appearance of irreversibly glycated albumin (AGE-Alb). These humoral changes coexisted with micro-and macroangiopathic lesions characteristic to both diseases, ie, capillary narrowing, hyperplasia of endothelial basal lamina, proliferation of perivascular extracellular matrix (abnormali-ties reminiscent of type I diabetes), and concomitant intimal accumulation of modified lipoproteins and macrophage-derived foam cells in the aorta, coronaries, and cardiac valves, leading to accelerated formation of atherosclerotic plaques. These changes eventually appeared in the D hamsters also, but at a much slower rate, whereas the H group showed only modifications characteristic for atherosclerosis. Our findings indicate that, overall, 1) diabetes accelerated the early development and progression of atherosclerotic lesions leading to rapid calcification, and 2) hyperlipidemia associated with diabetes accelerated the rate of development of diabetes-induced microvascular disease. The hamster model may be useful to study the impact of various drugs on the diabetes-related vascular complications.

Original languageEnglish (US)
Pages (from-to)997-1014
Number of pages18
JournalAmerican Journal of Pathology
Volume148
Issue number3
StatePublished - Mar 1 1996
Externally publishedYes

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Hyperlipidemias
Cricetinae
Heart Valves
Atherosclerosis
Animal Models
Diabetes Complications
Aorta
Tunica Intima
Foam Cells
Experimental Diabetes Mellitus
Lipid Peroxides
Mesocricetus
Atherosclerotic Plaques
Type 1 Diabetes Mellitus
Basement Membrane
Lipoproteins
Hyperplasia
Extracellular Matrix
Blood Vessels
Retina

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Simionescu, M., Popov, D., Sima, A., Hasu, M., Costache, G., Faitar, S., ... Simionescu, N. (1996). Pathobiochemistry of combined diabetes and atherosclerosis studied on a novel animal model: The hyperlipemic-hyperglycemic hamster. American Journal of Pathology, 148(3), 997-1014.

Pathobiochemistry of combined diabetes and atherosclerosis studied on a novel animal model : The hyperlipemic-hyperglycemic hamster. / Simionescu, Maya; Popov, Doina; Sima, Anca; Hasu, Mirela; Costache, Gabriela; Faitar, Silviu; Vulpanovici, Alexandra; Stancu, Camelia; Stern, David; Simionescu, Nicolae.

In: American Journal of Pathology, Vol. 148, No. 3, 01.03.1996, p. 997-1014.

Research output: Contribution to journalArticle

Simionescu, M, Popov, D, Sima, A, Hasu, M, Costache, G, Faitar, S, Vulpanovici, A, Stancu, C, Stern, D & Simionescu, N 1996, 'Pathobiochemistry of combined diabetes and atherosclerosis studied on a novel animal model: The hyperlipemic-hyperglycemic hamster', American Journal of Pathology, vol. 148, no. 3, pp. 997-1014.
Simionescu, Maya ; Popov, Doina ; Sima, Anca ; Hasu, Mirela ; Costache, Gabriela ; Faitar, Silviu ; Vulpanovici, Alexandra ; Stancu, Camelia ; Stern, David ; Simionescu, Nicolae. / Pathobiochemistry of combined diabetes and atherosclerosis studied on a novel animal model : The hyperlipemic-hyperglycemic hamster. In: American Journal of Pathology. 1996 ; Vol. 148, No. 3. pp. 997-1014.
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