Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice.
Two month old C57BL/6 mice were placed on three different diets: 1) normal diet (NC; 0.025% cholesterol), 2) hypercholesterolemic Western-type diet (HC-W; 0.2% cholesterol), and 3) hypercholesterolemic Paigen-type diet (HC-P; 1.25% cholesterol plus 0.5% cholic acid). At 6 months of age, the animals underwent ligation of the left carotid artery and were randomly assigned to vehicle (PBS, subcutaneous) or angiotensin II (Ang II; 1.4 mg/kg/day, subcutaneous) treatment for 4 weeks. Low density lipoprotein-cholesterol levels were similarly increased in both HC diets (NC, 4 +/- 3 mg/dl; HC-W, 123 +/- 17 mg/dl; HC-P, 160 +/- 14 mg/dl). However, the levels of high density lipoprotein-cholesterol (HDL-C) were reduced only in animals fed the HC-P diet (NC, 82 +/- 6 mg/dl; HC-W, 79 +/- 7 mg/dl; HC-P, 58 +/- 7 mg/dl). In Ang II-treated mice, carotid artery ligation induced intimal smooth muscle cell proliferation to a similar extent in NC- and HP-W-fed animals. However, a significantly larger intimal area developed in ligated vessels from Ang II-treated mice fed the HC-P diet (3.6-fold higher than in Ang II-treated NC mice). Together, these results show the accelerating effect of mild hypercholesterolemia, reduced HDL-C levels, and Ang II on intimal hyperplasia after carotid artery ligation in mice.
da Cunha
Valdeci
V
Department of Pharmacology, Berlex Bioscience, Richmond, CA, USA. valdeci_dacunha@yahoo.com
Martin-McNulty
Baby
B
Vincelette
Jon
J
Zhang
Lening
L
Rutledge
John C
JC
Wilson
Dennis W
DW
Vergona
Ronald
R
Sullivan
Mark E
ME
Wang
Yi-Xin
YX
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000601:surgery; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D004032:Diet; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000378:metabolism*; D006965:Hyperplasia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D008076:Cholesterol, HDL; D000804:Angiotensin II