Bone marrow transplantation as an established approach for understanding the role of macrophages in atherosclerosis and the metabolic syndrome

Aparicio-Vergara, Marcela; Shiri-Sverdlov, Ronit; Koonen, Debby P. Y.; Hofker, Marten H.

doi:10.1097/mol.0b013e3283508c4f

Cited by 9 publications

(10 citation statements)

References 70 publications

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“…After 8 weeks of HFD feeding, AIBP ΔBMK /LDLR −/− showed severe atherosclerotic lesions, inflammatory cell infiltration and polarization of macrophages to the proinflammatory phenotype compared with AIBP WT /LDLR −/− mice, indicating that intracellular AIBP may exert anantiatherosclerotic effect. A previous study has reported that BMT normally affects the development of aortic atherosclerosis in mice [ 40 ], but the application of this modality in atherosclerosis is mixed and warrants further investigation [ 41 , 42 ]. In the present study, we used mouse littermates with different genotypes and simultaneously performed BMT transplantation controls.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial apolipoprotein A-I binding protein alleviates atherosclerosis by regulating mitophagy and macrophage polarization

et al. 2022

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Apolipoprotein A-I binding protein (AIBP), a secreted protein, has been shown to play a pivotal role in the development of atherosclerosis. The function of intracellular AIBP, however, is not yet well characterized. Here, we found that AIBP is abundantly expressed within human and mouse atherosclerotic lesions and exhibits a distinct localization in the inner membrane of mitochondria in macrophages. Bone marrow-specific AIBP deficiency promotes the progression of atherosclerosis and increases macrophage infiltration and inflammation in low-density lipoprotein receptor-deficient (LDLR−/−) mice. Specifically, the lack of mitochondrial AIBP leads to mitochondrial metabolic disorders, thereby reducing the formation of mitophagy by promoting the cleavage of PTEN-induced putative kinase 1 (PINK1). With the reduction in mitochondrial autophagy, macrophages polarize to the M1 proinflammatory phenotype, which further promotes the development of atherosclerosis. Based on these results, mitochondrial AIBP in macrophages performs an antiatherosclerotic role by regulating of PINK1-dependent mitophagy and M1/M2 polarization.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial apolipoprotein A-I binding protein alleviates atherosclerosis by regulating mitophagy and macrophage polarization

et al. 2022

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“…In this study we examined the effects of macrophage deficiency of α7nAChR on the characteristics of early and advanced stage atherosclerotic lesions in low density lipoprotein receptor knockout (LDLRKO) mice. To that end, we utilized a bone marrow transplantation approach, a strategy used successfully by our laboratory and others to study the contribution of a particular gene expressed by macrophages to atherogenesis [ 15 , 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, the present studies as well as those by Johansson et al [ 13 ] and Kooijman et al [ 14 ] are based on a bone marrow transplantation approach that uses donors with global deficiency of α7nAChR. Whereas this strategy has been successfully used by us [ 15 ] and others [ 19 , 31 , 32 ] to evaluate the contribution of a particular gene expressed by macrophages to atherogenesis, it is difficult to conclude whether the reduction in advanced lesion burden and macrophage content in mice with bone marrow deficiency of α7nAChR is the result of the impact of α7nAChR deficiency on macrophage functions or whether cells other than macrophages also contribute to the observed phenotype. Future studies in mice with macrophage specific deletion of α7nAChR will provide more definitive answers to these questions.…”

Section: Discussionmentioning

confidence: 96%

Reduced Size and Macrophage Content of Advanced Atherosclerotic Lesions in Mice with Bone Marrow Specific Deficiency of Alpha 7 Nicotinic Acetylcholine Receptor

Lee

Vázquez

2015

PLoS ONE

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In macrophages the α7 nicotinic acetylcholine receptor (α7nAChR) modulates production of inflammatory cytokines, cholesterol accumulation and lipoprotein uptake. Recently, our laboratory showed that selective stimulation of the α7nAChR protects macrophages from apoptosis, an effect that is absent in α7nAChR-deficient macrophages. All these observations are suggestive of a potential role of macrophage α7nAChR in atherosclerosis. Mouse models of the disease with bone marrow deletion of α7nAChR represent an attractive approach to address the in vivo relevance of these in vitro findings. However, recent studies that focused on the impact of hematopoietic deficiency of α7nAChR on early atherosclerotic lesions of low density lipoprotein receptor knockout (LDLRKO) mice, yielded controversial results. The question also remained whether macrophage α7nAChR modulates the characteristics of advanced lesions. Here we used LDLR knockout mice transplanted with bone marrow from wild-type or α7nAChR knockout animals to revisit the effect of hematopoietic deficiency of α7nAChR on early lesions and to examine, for the first time, its impact on advanced plaques. Aortic sinus atherosclerotic lesions were analyzed following 8 and 14 weeks on a high fat diet. Early lesions in mice with α7nAChR deficient bone marrow were not different from those in control animals. However, advanced lesions of mice with bone marrow deletion of α7nAChR exhibited reduction in size, macrophage content and cell proliferation. These studies are the first in examining the impact of hematopoietic deficiency of α7nAChR on the characteristics of advanced atherosclerotic lesions in a mouse model of the disease and provide novel evidence underscoring a potential pro-atherogenic role of macrophage α7nAChR.

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“…This approach is standard in the atherosclerosis literature and is usually interpreted as indicating myeloid specificity and even implied specificity for macrophages. [30][31][32][33][34] Recipient Ldlr -/mice were preconditioned with lethal c-irradiation, then rescued by adoptive transfer of bone marrow from mice deficient in AMPK (Prkab1 -/-) or littermate matched (Prkab1 þ/þ ) controls. BMT was performed at age 12 weeks, and metformin treatment from age 14 weeks to age 25 weeks, allowing a prolonged period on metformin after BMT, when there was a cull for analysis as for the first cohort (Figure 2A).…”

Section: Atherosclerosis-prevention By Metformin Requires Haematopoietic Ampkmentioning

confidence: 99%

Metformin Directly Suppresses Atherosclerosis In Normoglycemic Mice Via Haematopoietic Adenosine Monophosphate-Activated Protein Kinase (Ampk)

et al. 2019

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Atherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque haemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and activating transcription factor 1 (ATF1). The antidiabetic drug metformin may also activate AMPK-dependent signalling. Hypothesis: Metformin systematically induces atheroprotective genes in macrophages via AMPK and ATF1, thereby suppresses atherogenesis.

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Bone marrow transplantation as an established approach for understanding the role of macrophages in atherosclerosis and the metabolic syndrome

Abstract: BMT is an efficient and versatile tool for assessing the roles of specific genes that are restricted to hematopoietic cells, and especially the monocytes and macrophages in metabolic syndrome and its related pathologies.

Cited by 9 publications

References 70 publications

Mitochondrial apolipoprotein A-I binding protein alleviates atherosclerosis by regulating mitophagy and macrophage polarization

Mitochondrial apolipoprotein A-I binding protein alleviates atherosclerosis by regulating mitophagy and macrophage polarization

Reduced Size and Macrophage Content of Advanced Atherosclerotic Lesions in Mice with Bone Marrow Specific Deficiency of Alpha 7 Nicotinic Acetylcholine Receptor

Metformin Directly Suppresses Atherosclerosis In Normoglycemic Mice Via Haematopoietic Adenosine Monophosphate-Activated Protein Kinase (Ampk)

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