Animal Models of Diabetic Macrovascular Complications: Key Players in the Development of New Therapeutic Approaches

Table 2

Atherosclerotic mouse models with increased atherosclerosis after diet-induced diabetes.

Mouse model	Inducer	Hyperlipidemia	Atherosclerosis	Comments	Reference
Diabetes increases atherosclerosis without changes in plasma lipids
ApoE^−/−	HFD; (17 wks)	TC↔ (15.6 mM); TG↔ (1.1 mM)	↑	Glucose↑, IR versus mice w/equal lipids on low-fat diet	[122]
LDLR^−/−	DD; (18–24 wks)	TC↔ (43.4 mM)	↑ (calcif.)	Glucose↑, IR	[123]
Diabetes increases atherosclerosis and alters plasma lipid levels
LDLR^−/−	WD; (17 wks)	TC↑ (27.0 mM); TG↑ (4.3 mM)	↑	Glucose↑, insulin↑, versus HFD w/o cholesterol + similar dysglycemia: lesions↑	[124]
LDLR^−/−	WD; (4.5 mos)	TC↑ (25.0 mM); TG↑ (2.6 mM)	↑	Insulin↑, IR; versus fructose diet w/equal cholesterol + euglycemia: lesions↔	[125]
LDLR^−/−	DD; (16 wks)	TC↑ (17.9 mM); TG↑ (5.0 mM)	↑	Glucose↑, insulin↑, IR	[126]
ApoE^−/−	WD; (5 wks)	TC↑ (33.8 mM); TG↑ (1.1 mM)	NI↑	Glucose↑, insulin↑	[127]
ApoE^*3-Leiden	HCD; (28 wks)	TC↑ (20 mM); TG↑ (1.7 mM)	↑	IR	[106]
HuB	HFD; (12 mos)	TC↑ (3.5 mM); TG↑ (1.0 mM)	Fatty streaks	Glucose↑, insulin↑, IR	[128]
ApoE^−/−	Fructose; (8 wks)	TC↔ (9.9 mM); TG↑ (2.1 mM)	↑	Glucose↑, insulin↑	[129]

DD, diabetogenic diet (Bioserve F1850: 35.5% energy from fat); HCD, high-cholesterol diet (20% energy from fat, 0.15–1.25% cholesterol); HFD, high-fat diet (20–60% energy from fat, usually no cholesterol); IR, insulin resistance; NI, neointima; TC, total cholesterol; TG, triglycerides; WD, Western diet (Harlan Teklad TD96125 or TD88137).