Diabetes-induced accelerated atherosclerosis in swine

Area of Science:

• Cardiovascular Science
• Metabolic Disease Research
• Animal Models in Atherosclerosis

Background:

• Diabetes mellitus is a significant risk factor for accelerated atherosclerotic cardiovascular disease.
• Existing humanoid animal models for studying diabetes-accelerated atherosclerosis are limited.
• Understanding the mechanisms requires a suitable, reproducible animal model.

Purpose of the Study:

• To establish and characterize a swine model of diabetes superimposed on hyperlipemia.
• To investigate the impact of diabetes and hyperlipemia on atherosclerosis development in swine.
• To provide a valuable tool for studying diabetes-accelerated atherosclerosis in a humanoid context.

Main Methods:

• Diabetes was induced in a swine model using streptozotocin (STZ), targeting beta-cells.
• Animals were maintained without insulin for up to 48 weeks, with plasma glucose and cholesterol monitored.
• Atherosclerosis progression was assessed by quantifying aortic sudanophilia, coronary artery stenosis, and lesion cholesterol content.

Main Results:

• Diabetic/hyperlipemic (D-HL) swine exhibited hypertriglyceridemia and a doubling of aortic sudanophilia compared to nondiabetic/hyperlipemic (N-HL) controls.
• Coronary artery stenosis was significantly higher in D-HL swine (86%) versus N-HL swine (46%) at 20 weeks.
• Aortic lesions in D-HL swine had double the cholesterol content, with increased oleate incorporation in aortic areas and monocytes.

Conclusions:

• A reproducible swine model of diabetes with hypertriglyceridemia and accelerated atherosclerosis has been successfully established.
• This model exhibits humanoid characteristics relevant to human diabetic cardiovascular complications.
• The model is valuable for elucidating mechanisms underlying accelerated atherosclerosis in diabetic individuals.