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

Table 3

Atherosclerotic mouse models with increased atherosclerosis after chemically induced diabetes.

Mouse model	Inducer	Hyperlipidemia	Atherosclerosis	Comments	Reference
Diabetes increases atherosclerosis without changes in plasma lipids
ApoE^−/−	STZ	TC↔ (9.1 mM); TG↔ (1.3 mM)	↑ × 2	Calcified lesions	[130]
ApoE^−/−GPx1^−/−	STZ	TC↔ (13.8 mM); TG↔ (2.1 mM)	↑ × 4		[131]
LDLR^+/−	STZ + CCA (12 wks)	TC↔ (14.1 mM); TG↔ (0.6 mM)	↑	Cholic acid	[132]
LDLR^+/−hAR	STZ + CCA (12 wks)	TC↔ (13.6 mM); TG↔ (0.6 mM)	↑ × 2	Cholic acid; versus LDLR^+/− + STZ: lipids↔, lesions↑ × 2	[132]
ApoE^−/−hAR	STZ	TC↔ (31.1 mM); TG↔ (3.1 mM)	↑ × 2		[133]
Diabetes increases atherosclerosis and alters plasma lipid levels
Balb/c	STZ + AD (12–20 wks)	TC↑ (9.8 mM); TG↑ (0.6 mM)	↑ × 17	Cholate	[134]
ApoE^−/−	STZ	TC↑ (35.3 mM); TG↔ (1.7 mM)	↑ × 5	sRAGE → lesions ↓	[135]
LDLR^−/−	STZ + WD; (6 wks)	TC↑ (44.3 mMl); TG↑ (6.3 mM)	↑ × 6.5		[136]
HuB/LPL^+/−	STZ + WD; (20 wks)	TC↑ (13.8 mM); TG↑ (5.5 mM)	↑ × 14		[137]
LDLR^−/−Apobec-1^−/−	STZ	TC↑ (9.9 mM); TG↔ (1.6 mM)	↑ × 1.5		[138]
LDLR^−/−	STZ + HCD (12 wks)	TC↑ (91.6 mM); TG↔ (1.3 mM)	↑ × 3		[132]
LDLR^−/−hAR	STZ + HCD (12 wks)	TC↑ (95.2 mM); TG↔ (1.0 mM)	↑ × 4	Versus LDLR^−/− + STZ: lipids↔, lesions↑ × 2	[132]

AD, atherogenic diet (12.5–40% energy from fat, 0.075–1.5% cholesterol, possibly with 0.5% sodium cholate); CCA, cholesterol/cholic acid–containing diet (1.25% cholesterol and 0.5% sodium cholate); HCD, high-cholesterol diet (20% energy from fat, 0.15–1.25% cholesterol); sRAGE, soluble receptor for AGEs; STZ, streptozotocin; TC, total cholesterol; TG, triglycerides; WD, Western diet (Harlan Teklad TD96125 or TD88137).