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.
Keywords: apoptosis; phospholipid transfer proteins.
© 2014 American Heart Association, Inc.