Phospholipid transfer protein destabilizes mouse atherosclerotic plaque.

Abstract

OBJECTIVE:

Phospholipid transfer protein (PLTP) accelerates the development of atherosclerosis in mouse models. We examined the role of PLTP in atherosclerotic plaque stability.

APPROACH AND RESULTS:

We prepared apolipoprotein E and PLTP double-knockout (PLTP(-/-)ApoE(-/-)) mice. PLTP deficiency significantly decreased lesion size and reduced monocyte/macrophage infiltration, as well as macrophage apoptosis in lesion areas. Moreover, it increased fibrous content in plaques, which suggests that PLTP may affect atherosclerotic plaque stability. Importantly, PLTP overexpression mediated by adenovirus had the reverse effect. It promoted the accumulation of reactive oxygen species in macrophages, which could lead to cell apoptosis and increased the production of inflammatory cytokines and chemokines. PLTP overexpression could promote receptor-interacting protein 3 recruitment of macrophages in cytoplasm, which could induce reactive oxygen species, thus inducing atherogenesis.

CONCLUSIONS:

PLTP plays an important role in modulating the stability of atherosclerotic plaques. The receptor-interacting protein 3- reactive oxygen species signal pathway could be involved in this PLTP-mediated process.

• Authors: Ke Zhang, Xiaoling Liu, Yang Yu, Tian Luo, Lin Wang, Chen Ge, Xinxin Liu, Jiantao Song, Xiancheng Jiang, Yun Zhang, Shucun Qin, Mei Zhang
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 34 Issue 12 Pg. 2537-44 (Dec 2014) ISSN: 1524-4636 [Electronic] United States
• PMID: 25324570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Apolipoproteins E
• Chemokines
• Cytokines
• Lipids
• Phospholipid Transfer Proteins
• Reactive Oxygen Species
• phospholipid transfer protein, mouse
• Receptor-Interacting Protein Serine-Threonine Kinases
• Ripk3 protein, mouse
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Apolipoproteins E (deficiency, genetics)
• Apoptosis
• Carotid Arteries (metabolism, pathology)
• Carotid Stenosis (genetics, metabolism, pathology)
• Caspase 3 (metabolism)
• Chemokines (blood)
• Cytokines (blood)
• Lipids (blood)
• Macrophages (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Phospholipid Transfer Proteins (deficiency, genetics, metabolism)
• Plaque, Atherosclerotic (genetics, metabolism, pathology)
• Reactive Oxygen Species (metabolism)
• Receptor-Interacting Protein Serine-Threonine Kinases (metabolism)
• Signal Transduction
• Up-Regulation