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

Table 4

Atherosclerotic mouse models with increased atherosclerosis after genetically induced diabetes.

Mouse model	Diet	Hyperlipidemia	Atherosclerosis	Comments	Reference
Diabetes increases atherosclerosis without changes in plasma lipids
LDLR^−/−GP		TC↔ (8.8 mM); TG↔ (2.1 mM)	↑ × 3		[139]
ApoE^−/−IRS2^−/−	WD; (9–12 wks)	TC↔ (64.9 mM); TG↔ (0.8 mM)	↑		[140]
ApoE^−/−IRS2^−/−	AD; (4 wks)	TC↔ (15.6 mM)	↑		[141]
ApoE^−/−Insr^+/−Irs1^+/−	WD; (15 wks)	TC↔ (24.0–30.9 mM); TG↔ (1.1–1.5 mM)	↑		[44]
Diabetes increases atherosclerosis and alters plasma lipid levels
LDLR^−/−ob/ob		TC↑ (44.5 mM); TG↑ (11.5 mM)	↑		[38]
LDLR^−/−GP	AD; (12 wks)	TC↑ (34.9 mM); TG↑ (23.8mM)	↑ × 2	Lesion hemorrhages↑	[139]
LDLR^−/−ob/ob		TC↑ (17.2 mM); TG↑ (3.4 mM)	↑ × 4		[36]
LDLR^−/−ApoB^100/100ob/ob		TC↑ (44.8 mM); TG↑ (7.4 mM)	↑	Versus C57Bl/6: Insulin↑, BP↑	[39]
ApoE^−/−db/db		TC↑ (15.1 mM); TG↑ (2.6 mM)	↑ × 3		[37]
ApoE^−/−db/db	WD; (10 wks)	TC↑ (37.9 mM); TG↑ (10.1 mM)	↑		[37]
ApoE^−/−db/db		TC↑ (24.8 mM); TG↔ (0.2 mM)	↑ × 3		[142]
ApoE^−/−db/db	Chow diet	TC↑ (30–40 mM); TG↔ (1-2 mM)	↑ × 3-4	C57BL/6 background	*
ApoE^−/−ob/ob		TC↑ (17.7 mM); TG↔ (1.5 mM)	↑ × 3		[36]
ApoE^−/−ApoB^100/100ob/ob		TC↑ (31.2 mM); TG↑ (3.8 mM)	↑	Versus C57Bl/6: glucose↑, insulin↑, IR, BP↑	[39]
LDLR^−/−Ins2^Akita	HCD; (16 wks)	TC↑ (32.5 mM); TG↑ (5.3 mM)	↑ × 2	Phenotype stronger in males	[25]
ApoE^−/−Ins2^Akita		TC↑ (22.5 mM); TG↑ (0.9 mM)	↑ × 3		[24]
E4hLDLR-tg; Ins2^Akita		TC↑ (2.6 mM); TG↔ (0.5 mM)	↑	Non-HDL-C/HDL-C ratio~3	[143]
KKAy^+ApoE^−/−		TC↑ (7.6 mM); TG↑ (1.3 mM)	↑		[41]
Trail^−/−ApoE^−/−	WD; (12 wks)	TC↑ (23 mM); TG↑ (2.2 mM)	↑		[144]

AD, atherogenic diet (10.8–40% energy from fat, 0.075–1.5% cholesterol, possibly with 0.5% sodium cholate); BP, blood pressure; E4, human ApoE^*4 allele; HCD, high-cholesterol diet (20% energy from fat, 0.15–1.25% cholesterol); hLDLR, human LDLR; TC, total cholesterol; TG, triglycerides; WD, Western diet (Harlan Teklad TD96125 or TD88137). ^*Hübschle T, Hiss K. unpublished data.