Lanatoside C Promotes Foam Cell Formation and Atherosclerosis.

ABSTRACT: Lanatoside C's impact on atherosclerosis is poorly understood. The present study was conducted to determine whether lanatoside C affects the development of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. ApoE(-/-) mice were administered either phosphate-buffered saline (PBS) containing 0.1% DMSO (the vehicle control group) or lanatoside C at low (1?mg/kg per day) or high (2?mg/kg per day) doses, and fed a Western diet for 12 weeks. Lanatoside C dose-dependently aggravated the development of atherosclerosis in the ApoE(-/-) mice compared with the vehicle control group. In an effort to determine the mechanism by which lanatoside C increased atherosclerosis, we found that lanatoside C significantly promoted the uptake of oxidised low-density lipoprotein (oxLDL) and increased foam-cell formation by upregulation of scavenger receptor class A (SR-A) and the class B scavenger receptor (CD36) in macrophages. Meanwhile, the effects of lanatoside C were abolished using small interfering RNA (siRNA) inhibition of peroxisome proliferator-activated receptors ?/? (PPAR?/?). Overall, our data demonstrate that lanatoside C aggravates the development of atherosclerosis by inducing PPAR?/? expression, which mediates upregulation of SR-A and CD36, and promotes oxLDL uptake and foam-cell formation.

SUBMITTER: Shi H 

PROVIDER: S-EPMC4731744 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other