Inducible phospholipid transfer protein deficiency ameliorates atherosclerosis.

Abstract

BACKGROUND AND AIMS:

Atherosclerosis progression and regression studies are related to its prevention and treatment. Although we have gained extensive knowledge on germline phospholipid transfer protein (PLTP) deficiency, the effect of inducible PLTP deficiency in atherosclerosis remains unexplored.

METHODS:

We generated inducible PLTP (iPLTP)-knockout (KO) mice and measured their plasma lipid levels after feeding a normal chow or a Western-type diet. Adenovirus associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9) was used to induce hypercholesterolemia in the mice. Collars were placed around the common carotid arteries, and atherosclerosis progression and regression in the carotid arteries and aortic roots were evaluated.

RESULTS:

On a normal chow diet, iPLTP-KO mice exhibited decreased cholesterol, phospholipid, apoA-I, and apoB levels compared with control mice. Furthermore, the overall amount of high-density lipoprotein (HDL) particles was reduced in these mice, but this effect was more profound for larger HDL particles. On a Western-type diet, iPLTP-KO mice again exhibited reduced levels of all tested lipids, even though the basal lipid levels were increased. Additionally, these mice displayed significantly reduced atherosclerotic plaque sizes with increased plaque stability. Importantly, inducible PLTP deficiency significantly ameliorated atherosclerosis by reducing the size of established plaques and the number of macrophages in the plaques without causing lipid accumulation in the liver.

CONCLUSIONS:

Induced PLTP deficiency in adult mice reduces plasma total cholesterol and triglycerides, prevents atherosclerosis progression, and promotes atherosclerosis regression. Thus, PLTP inhibition is a promising therapeutic approach for atherosclerosis.

• Authors: Ke Zhang, Jiao Zheng, Yunqin Chen, Jibin Dong, Zhiqiang Li, Yeun-Po Chiang, Mulin He, Qingxia Huang, Huiru Tang, Xian-Cheng Jiang
• Journal: Atherosclerosis (Atherosclerosis) Vol. 324 Pg. 9-17 (05 2021) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 33798923 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Phospholipid Transfer Proteins
• phospholipid transfer protein, mouse

Topics

• Animals
• Atherosclerosis (genetics, prevention & control)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phospholipid Transfer Proteins (genetics)