| RRC ID |
67818
|
| Author |
Koga M, Kanaoka Y, Okamoto M, Nakao Y, Inada K, Takayama S, Kataoka Y, Yamauchi A.
|
| Title |
Varenicline aggravates atherosclerotic plaque formation in nicotine-pretreated ApoE knockout mice due to enhanced oxLDL uptake by macrophages through downregulation of ABCA1 and ABCG1 expression.
|
| Journal |
J Pharmacol Sci
|
| Abstract |
Varenicline is a widely used and effective drug for smoking cessation. We previously reported that varenicline aggravates atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. However, it remains unknown whether varenicline affects cardiovascular events in patients with nicotine addiction. Here, we examined the effect of varenicline on atherosclerotic plaque formation in nicotine-pretreated ApoE KO mice and oxidized low-density lipoprotein (oxLDL) uptake in nicotine-treated peritoneal macrophages. Varenicline caused significant progression of plaque formation in the whole aorta and aortic root and further accelerated the increased formation of a macrophage-rich plaque area in the aortic root in nicotine-pretreated ApoE KO mice. Varenicline (10 μM) enhanced oxLDL uptake in peritoneal macrophages. Furthermore, this treatment significantly further lowered the decreased protein levels of ATP-binding cassette (ABC) transporter without affecting the expression of scavenger receptors LOX-1 and CD36 in RAW264.7 cells treated with 100 nM nicotine. Varenicline enhanced nicotine-induced oxLDL uptake in macrophages through decreased expression of cholesterol efflux transporters ABCA1 and ABCG1 and thereby progressed atherosclerotic plaque formation. Taken together, we tentatively conclude that nicotine exposure before and/or during varenicline treatment can aggravate varenicline-increased atherosclerotic plaque formation and progression. Therefore, this enhanced risk requires special consideration when prescribing varenicline to smoker patients.
|
| Volume |
142(1)
|
| Pages |
9-15
|
| Published |
2020-1-1
|
| DOI |
10.1016/j.jphs.2019.11.002
|
| PII |
S1347-8613(19)35727-5
|
| PMID |
31771811
|
| MeSH |
ATP Binding Cassette Transporter 1 / genetics
ATP Binding Cassette Transporter 1 / metabolism*
ATP Binding Cassette Transporter, Subfamily G, Member 1 / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism*
Animals
Down-Regulation
Gene Expression Regulation / drug effects
Lipoproteins, LDL / metabolism
Macrophages / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout, ApoE
Nicotine / agonists
Nicotine / pharmacology*
Plaque, Atherosclerotic / etiology*
RAW 264.7 Cells
Smoking Cessation Agents / toxicity
Varenicline / toxicity*
|
| IF |
2.835
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535) |
