Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout mice via macrophage effects

Atherosclerosis is considered to be a chronic inflammatory disease that can lead to severe clinically important cardiovascular events. miR-150 is a small noncoding RNA that significantly enhances inflammatory responses by upregulating endothelial cell proliferation and migration, as well as intravascular environmental homeostasis. However, the exact role of miR-150 in atherosclerosis remains unknown. Here, we investigated the effect of miR-150 deficiency on atherosclerosis development. Using double-knockout (miR-150−/− and ApoE−/−) mice, we measured atherosclerotic lesion size and stability. Meanwhile, we conducted in vivo bone marrow transplantation to identify cellular-level components of the inflammatory response. Compared with mice deficient only in ApoE, the double-knockout mice had significantly smaller atherosclerotic lesions and displayed an attenuated inflammatory response. Moreover, miR-150 ablation promoted plaque stabilization via increases in smooth muscle cell and collagen content and decreased macrophage infiltration and lipid accumulation. The in vitro experiments indicated that an inflammatory response with miR-150 deficiency in atherosclerosis results directly from upregulated expression of the cytoskeletal protein, PDZ and LIM domain 1 (PDLIM1), in macrophages. More importantly, the decreases in phosphorylated p65 expression and inflammatory cytokine secretion induced by miR-150 ablation were reversed by PDLIM1 knockdown. These findings suggest that miR-150 is a promising target for the management of atherosclerosis. Atherosclerosis is considered to be a chronic inflammatory disease that can lead to severe clinically important cardiovascular events. miR-150 is a small noncoding RNA that significantly enhances inflammatory responses by upregulating endothelial cell proliferation and migration, as well as intravascular environmental homeostasis. However, the exact role of miR-150 in atherosclerosis remains unknown. Here, we investigated the effect of miR-150 deficiency on atherosclerosis development. Using double-knockout (miR-150−/− and ApoE−/−) mice, we measured atherosclerotic lesion size and stability. Meanwhile, we conducted in vivo bone marrow transplantation to identify cellular-level components of the inflammatory response. Compared with mice deficient only in ApoE, the double-knockout mice had significantly smaller atherosclerotic lesions and displayed an attenuated inflammatory response. Moreover, miR-150 ablation promoted plaque stabilization via increases in smooth muscle cell and collagen content and decreased macrophage infiltration and lipid accumulation. The in vitro experiments indicated that an inflammatory response with miR-150 deficiency in atherosclerosis results directly from upregulated expression of the cytoskeletal protein, PDZ and LIM domain 1 (PDLIM1), in macrophages. More importantly, the decreases in phosphorylated p65 expression and inflammatory cytokine secretion induced by miR-150 ablation were reversed by PDLIM1 knockdown. These findings suggest that miR-150 is a promising target for the management of atherosclerosis. Cardiovascular disease is the leading cause of death among a variety of chronic noncommunicable diseases affecting patients worldwide (1.Benjamin E.J. Blaha M.J. Chiuve S.E. Cushman M. Das S.R. Deo R. de Ferranti S.D. Floyd J. Fornage M. Gillespie C. et al.Heart disease and stroke statistics-2017 update: a report from the American Heart Association.Circulation. 2017; 135: e146-e603Crossref PubMed Scopus (6296) Google Scholar). Atherosclerosis, the critical pathophysiological process underlying CVD, is well-recognized as a complex multifactorial disease and is generally considered a chronic inflammatory response (2.Ross R. Atherosclerosis–an inflammatory disease.N. Engl. J. Med. 1999; 340: 115-126Crossref PubMed Scopus (19241) Google Scholar) that can lead to several severe clinical cardiovascular events, such as myocardial infarction, sudden cardiac death, and stroke. During the initiation of atherosclerosis, the injured endothelial cells attract circulating monocytes by expressing chemokines and adhesion molecules, which also mediate the adhesion and rolling of monocytes on endothelium. The monocytes subsequently migrate through the endothelium and differentiate into macrophages, a process that gives rise to foam cells following the excess engulfment of oxidized LDL (Ox-LDL). The continuous intensification of the inflammatory response from endothelium and macrophages promotes the expansion of vascular smooth muscle cells (VSMCs), accumulation of more macrophages, development of atherosclerotic plaques, and the formation of necrotic cores and vulnerable plaques (3.Kim C.H.J. Mitchell J.B. Bursill C.A. Sowers A.L. Thetford A. Cook J.A. van Reyk D.M. Davies M.J. The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE-/- mice.Atherosclerosis. 2015; 240: 234-241Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar). Therefore, exploring and targeting the key regulators of atherosclerosis-related inflammation may provide clinicians with an effective strategy for preventing atherosclerosis. The effectiveness of anti-inflammation has been verified recently by a clinical study (4.Weber C. von Hundelshausen P. CANTOS trial validates the inflammatory pathogenesis of atherosclerosis: setting the stage for a new chapter in therapeutic targeting.Circ. Res. 2017; 121: 1119-1121Crossref PubMed Google Scholar), further strengthening the urgency of elucidating the mechanism underlying the development of inflammation during atherogenesis. microRNAs are a class of small noncoding RNAs that are widely present in eukaryotic organisms and have important regulatory effects on cell metabolism, cell development, tumorigenesis, and immune inflammation (5.Kluiver J.L. Chen C.Z. MicroRNAs regulate B-cell receptor signaling-induced apoptosis.Genes Immun. 2012; 13: 239-244Crossref PubMed Scopus (24) Google Scholar, 6.Lin Y.C. Kuo M.W. Yu J. Kuo H.H. Lin R.J. Lo W.L. Yu A.L. c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development.Mol. Biol. Evol. 2008; 25: 2189-2198Crossref PubMed Scopus (92) Google Scholar, 7.Haga H. Yan I. Takahashi K. Wood J. Patel T. Emerging insights into the role of microRNAs in the pathogenesis of cholangiocarcinoma.Gene Expr. 2014; 16: 93-99Crossref PubMed Scopus (20) Google Scholar). microRNAs fulfill their biological functions by negatively regulating the mRNA of their target molecules and have thus emerged as novel biomarkers for the diagnosis of various diseases and regulators of the progression of these diseases (8.Wang W. Zhang Y. Wang D. Gao S. Wang X. Gao H. Wang L. Prognostic role of microRNA-150 in various carcinomas: a meta-analysis.Onco Targets Ther. 2016; 9: 1371-1379Crossref PubMed Scopus (15) Google Scholar). miR-150 is a 22-nucleotide microRNA and is highly expressed in human lymph nodes, spleen, mature lymphocytes, regulatory T cells, and B cells under physiological conditions (9.Mi Q-S. Xu Y-P. Qi R-Q. Shi Y-L. Zhou L. Lack of microRNA miR-150 reduces the capacity of epidermal Langerhans cell cross-presentation.Exp. Dermatol. 2012; 21: 876-877Crossref PubMed Scopus (29) Google Scholar). miR-150 has also been shown to be upregulated in peripheral blood in patients with coronary heart disease (CHD) (10.Zeller T. Keller T. Ojeda F. Reichlin T. Twerenbold R. Tzikas S. Wild P.S. Reiter M. Czyz E. Lackner K.J. et al.Assessment of microRNAs in patients with unstable angina pectoris.Eur. Heart J. 2014; 35: 2106-2114Crossref PubMed Scopus (115) Google Scholar, 11.Huan T. Rong J. Tanriverdi K. Meng Q. Bhattacharya A. McManus D.D. Joehanes R. Assimes T.L. McPherson R. Samani N.J. et al.Dissecting the roles of microRNAs in coronary heart disease via integrative genomic analyses.Arterioscler. Thromb. Vasc. Biol. 2015; 35: 1011-1021Crossref PubMed Scopus (46) Google Scholar). Previous studies have demonstrated that miR-150 plays important roles in regulating endothelial cell proliferation and migration and intravascular environmental homeostasis (12.Zhang Y. Liu D. Chen X. Li J. Li L. Bian Z. Sun F. Lu J. Yin Y. Cai X. et al.Secreted monocytic miR-150 enhances targeted endothelial cell migration.Mol. Cell. 2010; 39: 133-144Abstract Full Text Full Text PDF PubMed Scopus (995) Google Scholar, 13.Li J. Zhang Y. Liu Y. Dai X. Li W. Cai X. Yin Y. Wang Q. Xue Y. Wang C. et al.Microvesicle-mediated transfer of microRNA-150 from monocytes to endothelial cells promotes angiogenesis.J. Biol. Chem. 2013; 288: 23586-23596Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 14.Zhao Y. Li Y. Luo P. Gao Y. Yang J. Lao K-H. Wang G. Cockerill G. Hu Y. Xu Q. et al.XBP1 splicing triggers miR-150 transfer from smooth muscle cells to endothelial cells via extracellular vesicles.Sci. Rep. 2016; 6: 28627Crossref PubMed Scopus (27) Google Scholar). In addition, miR-150-knockout mice displayed exacerbated obesity, tissue inflammation, and insulin resistance (15.Ying W. Tseng A. Chang R.C-A. Wang H. Lin Y-l. Kanameni S. Brehm T. Morin A. Jones B. Splawn T. et al.miR-150 regulates obesity-associated insulin resistance by controlling B cell functions.Sci. Rep. 2016; 6: 20176Crossref PubMed Scopus (54) Google Scholar). Ox-LDL-mediated lipoprotein accumulation in macrophages is attenuated by miR-150 in vitro (16.Li J. Zhang S. microRNA-150 inhibits the formation of macrophage foam cells through targeting adiponectin receptor 2.Biochem. Biophys. Res. Commun. 2016; 476: 218-224Crossref PubMed Scopus (22) Google Scholar). Nevertheless, the specific role of miR-150 in atherosclerosis development has not been elucidated. The present study showed that miR-150 expression was significantly upregulated in plaques from human patients with CHD and high-fat diet (HFD)-treated ApoE−/− mice. Specifically, miR-150 expression was upregulated in bone marrow-derived macrophages (BMDMs) upon Ox-LDL stimulation. miR-150 deficiency not only attenuated atherosclerotic plaque formation by decreasing inflammatory cytokine production but also protected against vulnerable plaque formation. By performing bone marrow transplantation and in vitro experiments, we showed that the effects of miR-150 on atherogenesis were largely dependent on its effects in macrophages, phenomena accompanied by inflammation alleviation. We noticed that miR-150 ablation reduced phosphorylated p65 expression, inflammatory cytokine secretion, and macrophage infiltration by directly upregulating PDZ and LIM domain 1 (PDLIM1) expression. The animal study procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee of the Renmin Hospital. miR-150-knockout mice were purchased from the Jackson Laboratory (007750). To purify the background, the female mice on a were with and the mice were with female mice for the mice. The mice were with mice the these mice were to mice. ApoE−/− mice and mice were to mice and ApoE−/− mice were into which were a and for to These mice were via the of the of tissue a for the mice were through of were with through the and from the of the the was with and atherosclerotic lesion were as H. W.L. X. Wang C. Z. Li H. of regulatory against atherosclerosis in 2017; PubMed Scopus (22) Google Scholar). The heart and were subsequently and in for of the and the of heart were the were with for for collagen and for lipid accumulation The plaque muscle cell collagen lipid W. K. S. C. M. S. K. C. A. atherosclerosis in PubMed Scopus Google Scholar). were for were W.L. Wang Wang T. Zhang Y. C. Li H. Y. of against atherosclerosis in J. 2015; PubMed Scopus Google Scholar). were in with for 1 and with the following and muscle The were with the following and were with a and were with were from the the mice were under The were by for and were to lipid and inflammatory cytokine In the bone marrow transplantation ApoE−/− mice were with a of of of of marrow cells from the and of mice ApoE−/−) were under and was with bone marrow cells through the genomic was from peripheral blood and was The mice were subsequently a for an for mRNA was by in and into with a as Zhang Yan Zhang P. Yang X. J. S. et and in mice and Med. 2017; PubMed Scopus Google Scholar). The expression of the target were by 1 and a The of the target were against of were by The were by and to which were in for 1 with the The were with the and with with The expression of specific were against of were and from the and of and ApoE−/− mice under bone marrow cells were from and in of with and The specific for PDLIM1 and the were purchased from The were with the molecules to the The cells were with Ox-LDL for of human studies were conducted in accordance with the in the of and were approved by the of Renmin of The coronary of patients with CHD had heart transplantation were the of the plaques The for these experiments were from were for was from the were and are as the were by among were by was considered To the role of miR-150 in we miR-150 expression was in atherosclerotic The of coronary from and patients with CHD were to the in miR-150 expression the demonstrated the of in the from the patients with The plaques in these a and lipid cores that miR-150 expression was significantly upregulated in the of patients with CHD To the in miR-150 expression in the atherosclerotic plaques from the were with in the atherosclerotic plaques from the mice were with for a for ApoE−/− mice displayed plaques mice, as shown in the miR-150 expression were upregulated in ApoE−/− mice to in mice, which with of We also the in miR-150 expression in and We that miR-150 expression significantly in but not in upon Ox-LDL stimulation. These findings suggest that miR-150 is in the development of atherosclerosis by in macrophages. To the of miR-150 to plaque we mice with ApoE−/− mice and mice. We that the of the atherosclerotic lesions in the were significantly decreased in mice with ApoE−/− mice of in lesion the were on We further plaque formation in the of the and to the effect of miR-150 on atherogenesis in mice. demonstrated that and lesion were significantly decreased in mice with ApoE−/− mice is a for atherosclerosis were the with to and and lipoprotein and plaques can the of plaques, collagen and macrophages, are more the size of plaques for the with clinical The composition of the collagen to that in smooth is the of plaque stability. We that and collagen were in mice with ApoE−/− mice We also noticed that the of macrophages and lipid accumulation were decreased in the of the of plaque were in miR-150 ablation to the plaque these that miR-150 deficiency was effective in atherosclerotic plaque stability. that inflammation is an important of atherosclerosis development, we the expression of cytokine in the of We measured the and mRNA of We that mRNA of and in the were decreased in mice with ApoE−/− mice of 1 and were significantly in the mice with in the ApoE−/− miR-150 expression was upregulated in as shown in we investigated miR-150 deficiency in cells to the development of the in the mice. We bone marrow from ApoE−/− into ApoE−/− mice and the mice with a for The of the was by the genomic from the blood cells We that miR-150 deficiency in macrophages attenuated atherosclerotic plaque development the and Moreover, the of infiltration of macrophages, secretion, and phosphorylated p65 indicated that miR-150 deficiency in macrophages significantly inflammatory responses These results indicated that the of miR-150 expression in bone marrow-derived cells was for the effects of miR-150 We the secretion of inflammatory from from ApoE−/− mice and that several such as and were is widely as an important in the of inflammation in the development of atherosclerosis. showed that phosphorylated and p65 were decreased in from mice with from ApoE−/− mice we also that mRNA expression was reduced in from mice is critical for the of monocytes in peripheral blood and the formation of macrophages in we macrophage infiltration and that miR-150 deficiency significantly macrophage migration To the mechanism by which miR-150 macrophage we performed the The results indicated that PDLIM1 a for miR-150 in the Using we demonstrated that miR-150 promoted PDLIM1 and that effect was the the PDLIM1 were We also that PDLIM1 expression was upregulated in the of mice study the PDLIM1 phosphorylated p65 and as well as secretion R. T. T. PDLIM1 inhibits inflammatory by the p65 of in the Rep. 2015; PubMed Google Scholar). we that phosphorylated p65 expression was by PDLIM1 and that the in p65 expression by miR-150 ablation was by PDLIM1 deficiency We also the expression of several of and These are also important of inflammatory response. we that and were significantly in the of mice that these molecules were not for miR-150 in We also PDLIM1 was in the decreases in secretion and macrophage infiltration by miR-150 We that PDLIM1 reversed the expression and macrophage infiltration by miR-150 ablation these findings that the effects of miR-150 deficiency on atherogenesis were by the upregulated expression of its target In the we demonstrated that miR-150 deficiency which were accompanied by inflammation and plaque we also verified that the effects of miR-150 ablation on atherogenesis were largely to its effects on macrophages, its effects on the of the inflammatory response and macrophage The of miR-150 attenuated increases in phosphorylated p65 expression, inflammatory cytokine secretion and macrophage infiltration by directly upregulating PDLIM1 expression. During the studies have demonstrated that various microRNAs are widely in human H. Yan I. Takahashi K. Wood J. Patel T. Emerging insights into the role of microRNAs in the pathogenesis of cholangiocarcinoma.Gene Expr. 2014; 16: 93-99Crossref PubMed Scopus (20) Google Scholar, B. K.J. MicroRNAs in the and of J. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar, T. of in by Expr. 2014; 16: PubMed Scopus Google Scholar, K. of noncoding RNAs as and therapeutic for Expr. 2015; 16: PubMed Scopus Google Scholar), and that of the human is under microRNA target and regulatory Full Text Full Text PDF PubMed Scopus Google Scholar). Atherosclerosis is as a complex multifactorial and microRNAs have emerged as important regulators of atherosclerosis development P. A. C. and microRNAs in 2015; PubMed Scopus Google Scholar). miR-150 is an emerged microRNA of in that is to be highly expressed in lymph nodes, the spleen, mature lymphocytes, regulatory T cells, and B cells (9.Mi Q-S. Xu Y-P. Qi R-Q. Shi Y-L. Zhou L. Lack of microRNA miR-150 reduces the capacity of epidermal Langerhans cell cross-presentation.Exp. Dermatol. 2012; 21: 876-877Crossref PubMed Scopus (29) Google Scholar). However, several have that miR-150 is also expressed in human microRNA expression is upregulated in patients with elevation myocardial and unstable angina R. C. H. G. L. Li L. of circulating and miR-150 in patients with myocardial 2015; PubMed Scopus Google Scholar, A. Chen Chang Chen to identify microRNAs as biomarkers for myocardial Res. 2014; PubMed Scopus Google miR-150 expression is in patients with heart D. F. A. M. R. L. as a novel for heart a Heart 2017; Full Text Full Text PDF PubMed Scopus Google Scholar). from the of patients with atherosclerosis that more miR-150 can atherogenesis (12.Zhang Y. Liu D. Chen X. Li J. Li L. Bian Z. Sun F. Lu J. Yin Y. Cai X. et al.Secreted monocytic miR-150 enhances targeted endothelial cell migration.Mol. Cell. 2010; 39: 133-144Abstract Full Text Full Text PDF PubMed Scopus (995) Google Scholar). In we showed that miR-150 expression was significantly in patients with We results in the experiments mice. These suggest that miR-150 is to cardiovascular More importantly, studies have that miR-150 plays important physiological roles in cell (5.Kluiver J.L. Chen C.Z. MicroRNAs regulate B-cell receptor signaling-induced apoptosis.Genes Immun. 2012; 13: 239-244Crossref PubMed Scopus (24) Google Scholar) and Z. Wang Y. X. X. Y. Li Y. M. J. K. Sun S. et al.miR-150 inhibits proliferation and 2015; 6: PubMed Scopus (22) Google Scholar) and also plays key regulatory roles in migration, cell and myocardial Z. P. Wang S. J. Sun Y. Zhang A. L. C. X. Wang K. et the heart from by accumulation in a of myocardial 2015; PubMed Scopus (54) Google Scholar). Using mice, we that miR-150 deficiency atherosclerosis development by inflammatory cytokine we that miR-150 expression significantly in upon Ox-LDL and that the effects of miR-150 ablation on atherogenesis were largely dependent on its effects on macrophages. Specifically, miR-150 ablation attenuated the inflammatory response and macrophage Therefore, study that the of miR-150 expression was in the development of atherosclerosis and that miR-150 atherosclerosis development through its effects on macrophages. studies have demonstrated that miR-150 in atherosclerotic conditions and as well as endothelial cell miR-150 can Ox-LDL-mediated lipoprotein accumulation in macrophages in that miR-150 may regulate atherogenesis by in cell Nevertheless, present study double-knockout mice to the role of miR-150 deficiency on the development of atherosclerosis in The results indicated that the effects of miR-150 deficiency on atherogenesis were largely dependent on its on inflammatory response in macrophages. is that microRNAs are of regulating target expression by to the of their target and that microRNAs are in negatively regulating expression the microRNAs cause the of the of the target and the pathophysiological of the cells, and B. K.J. MicroRNAs in the and of J. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar, A. Z. as of in the microRNA expression 2016; PubMed Scopus (27) Google Scholar, X. J.L. MicroRNAs in Med. 2017; PubMed Scopus Google Scholar). miR-150 to roles in various pathophysiological by targeting In the immune miR-150 prevents B cell development by targeting c-Myb C. G. Wang J. K. B cell by targeting the Full Text Full Text PDF PubMed Scopus Google Scholar), regulates T cell by targeting and enhances bone marrow-derived cell and migration by targeting W. Wang Y. Zhang C. Zhang D. Sun C. M. Zhang Z. X. B. Chen W. et inflammatory cytokine production by targeting 2016; PubMed Scopus Google Scholar, M. microRNA-150 regulates and migration of bone marrow-derived cells by targeting 6: PubMed Scopus Google Scholar). miR-150 deficiency endothelial cell by targeting B. Y. L. Lu T. Lin Y. Yang H. Lu Z. and modulates the induced by in endothelial Cell. 2017; PubMed Scopus Google Scholar), modulates endothelial cell by targeting reduces c-Myb expression, and enhances endothelial cell migration (12.Zhang Y. Liu D. Chen X. Li J. Li L. Bian Z. Sun F. Lu J. Yin Y. Cai X. et al.Secreted monocytic miR-150 enhances targeted endothelial cell migration.Mol. Cell. 2010; 39: 133-144Abstract Full Text Full Text PDF PubMed Scopus (995) Google Scholar, Z. G. Wang G. X. S. Xu Q. Wang W. Q. and an important role in endothelial cell and by targeting 2013; PubMed Scopus Google Scholar). miR-150 inhibits macrophage foam cell formation by targeting adiponectin receptor (16.Li J. Zhang S. microRNA-150 inhibits the formation of macrophage foam cells through targeting adiponectin receptor 2.Biochem. Biophys. Res. Commun. 2016; 476: 218-224Crossref PubMed Scopus (22) Google Scholar). Using in target and we that PDLIM1 was the target significantly upregulated in the of mice and that PDLIM1 was by miR-150 these were by the of the the PDLIM1 Moreover, we that and which important roles in macrophage and plaque progression R. M. A. Emerging of receptor and its in cardiovascular 2016; PubMed Scopus Google Scholar, C. S. M. T. A. B. R. A. A. Z. of and and and atherosclerosis in 2008; PubMed Scopus Google Scholar, I. death and inflammation in 2010; PubMed Scopus Google Scholar), were in the of mice. In a PDLIM1 decreased phosphorylated p65 expression and attenuated R. T. T. PDLIM1 inhibits inflammatory by the p65 of in the Rep. 2015; PubMed Scopus Google Scholar). results were with as we that the decreases in phosphorylated p65 expression, inflammatory and macrophage infiltration by miR-150 deficiency were largely reversed by PDLIM1 we that miR-150 deficiency against atherosclerosis in by upregulating PDLIM1 expression, a that to decreased cytokine and secretion and decreased macrophage plaque is the important cause of clinical cardiovascular events. engulfment and important roles in plaque formation and C. M. A. D. A.L. A. G. A. E. et of by a receptor increases the of cells by human Res. PubMed Scopus Google Scholar, I. G. insights into the of Biol. 2015; PubMed Scopus Google Scholar). foam cell to to the formation of necrotic cores in plaques L. and necrotic development in atherosclerosis: a with clinical to and J. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar, E. D. D.M. G. I. receptor reduces and promotes cell accumulation and plaque in atherosclerotic lesions of Thromb. Vasc. Biol. 2008; PubMed Scopus Google Scholar). in plaques the of the also macrophage and thus the size of the necrotic Q. of monocytes with vascular smooth muscle cells regulates and through Thromb. Vasc. Biol. PubMed Scopus Google Scholar). studies have indicated that microRNA expression, M. E. C. P. of in monocytes during is with of the but not insulin of 2012; PubMed Scopus Google Scholar) and H. E. Li Y. Sun C. G. A. A. C. et enhances in atherosclerotic Res. 2017; PubMed Scopus Google Scholar) expression, may be to plaque stability. In we that miR-150 deficiency plaque a by increases in collagen and content and decreases in macrophage infiltration and lipid accumulation. Moreover, miR-150 ablation the of inflammatory such as and these suggest that miR-150 deficiency is effective in atherosclerotic plaque stability. In we demonstrated that miR-150 deficiency inhibits atherosclerosis development and inflammatory secretion and promotes plaque stability. The effect of miR-150 ablation was reversed by directly PDLIM1 expression. study that miR-150 is an important novel target for the clinical and of atherosclerosis. bone marrow-derived macrophage coronary heart disease high-fat diet 1 oxidized LDL PDZ and LIM domain 1 smooth muscle cell vascular smooth muscle cell