Dual effects of miR-155 on macrophages at different stages of atherosclerosis: LDL is the key?
Atherosclerosis is a chronic, maladaptive, nonresolving inflammatory response which underlies the leading cause of death in the world today. During the process, macrophages play a central role in both the initiation and development stages of disease pathogenesis. MicroRNAs are a class of small non-coding RNAs that regulate almost all biological processes. MiR-155 is multi-target molecule specifically expressed in atherosclerotic plaques and pro-inflammatory macrophages. However, the effects of miR-155 on atherogenesis have been controversial. Several lines of evidence collectively indicated that, both as inducers and carriers of miR-155, LDL and its oxidized derivatives could modulate miR-155-mediated inflammatory and apoptotic responses in lesional macrophages at different stages of atherosclerosis. During early lesion formation, both native and mildly-oxidized LDL facilitated endogenous miR-155-mediated macrophage activation and recruitment. In the meantime, they may also increase the accumulation of exogenous LDL-bound miR-155, along with lipid intake and foam cell formation. During advanced stages, the levels of exogenous miR-155 and extensively-oxidized LDL could gradually increase and become highly enough to synergistically induce macrophage apoptosis and atheroma formation. Taken together, we hypothesized that native LDL and oxidized LDL played a key role in modulating the effects of miR-155 on macrophages at different stages of atherosclerosis.
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Rd, Beijing 100037, China.
Erli
E
Zhang
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Rd, Beijing 100037, China. Electronic address: aricho1985@163.com.
Yongjian
Y
Wu
D050197:Atherosclerosis / Q000503:physiopathology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*
D008077:Lipoproteins, LDL; C524942:MIRN155 microRNA, human; D035683:MicroRNAs