NO-1886 upregulates ATP binding cassette transporter A1 and inhibits diet-induced atherosclerosis in Chinese Bama minipigs.
It is widely believed that high density lipoprotein-cholesterol (HDL-C) functions to transport cholesterol from peripheral cells to the liver by reverse cholesterol transport (RCT), a pathway that may protect against atherosclerosis by clearing excess cholesterol from arterial cells. A cellular ATP binding cassette transporter called ABCA1 mediates the first step of RCT. NO-1886 has been proven to be highly effective at increasing HDL-C and reducing atherosclerosis. However, the mechanism of atherosclerosis inhibition for NO-1886 is not fully understood. In this study, the effects of NO-1886 on ABCA1 were investigated in high-fat/high-sucrose/high-cholesterol-fed Chinese Bama minipigs. Administration of NO-1886 (0.1 g/kg body weight/day) in the diet for 5 months significantly reduced atherosclerosis lesions and significantly increased plasma HDL-C and apolipoprotein A-I levels. The mRNA and protein levels of ABCA1 in the liver, retroperitoneal adipose tissue, and aorta were increased by NO-1886 as well. Multivariate linear regression analysis showed that the levels of LPL in plasma and the levels of ABCA1 in aorta were independently associated with the atherosclerotic lesion area. In addition, NO-1886 upregulated liver X receptor alpha and affected the expression of scavenger receptor class B type I in the liver. These results demonstrate that the mechanism of atherosclerosis inhibition for NO-1886 is associated with its effect on ABCA1.
Zhang
Chi
C
Institute of Cardiovascular Research, Nanhua University Medical School, Hengyang, Hunan 421001, China.
Yin
Weidong
W
Liao
Duanfang
D
Huang
Liang
L
Tang
Chaoke
C
Tsutsumi
Kazuhiko
K
Wang
Zongbao
Z
Liu
Yi
Y
Li
Qinkai
Q
Hou
Hongjie
H
Cai
Manbo
M
Xiao
Junxia
J
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000097:blood; D050197:Atherosclerosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D015999:Multivariate Analysis; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature; D014280:Triglycerides / Q000097:blood
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001549:Benzamides; D001786:Blood Glucose; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D009943:Organophosphorus Compounds; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014280:Triglycerides; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide