ABC Transporters, Cholesterol Efflux, and Implications for Cardiovascular Diseases

Wang, Nan; Westerterp, Marit

doi:10.1007/978-981-15-6082-8_6

Cited by 51 publications

(40 citation statements)

References 125 publications

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“…In advanced atheromata, in contrast to previous views on macrophage proliferation, macrophages can proliferate inside the lesions, through an Scavenger Receptor Class A (SRA)-dependent pathway (71,93,94). Cytokines related to leukopoiesis and monocyte mobilization from BM, like M-CSF, G-CSF, and MCP-1, are produced in an enhanced manner by macrophages carrying Abca1/Abcg1 deletion, supporting the role of the dyslipemia in these processes (25,27,44,95). Mouse models that were deficient in these genes had hematopoietic progenitors and/or monocyte-derived cells more prone to accumulate cholesterol and consequently, to transport cholesterol to atherosclerotic lesions (83,95,96).…”

Section: Contribution Of Splenic Neutrophilia and Monocytosis To Athementioning

confidence: 89%

“…It occurs when there is an insufficient or irregular production of blood cells from the BM (1,18,(21)(22)(23). The most common triggers of EMH are certain chronic hematological disorders, such as chronic hemolytic anemias, thalassemias, myelofibrosis, atherogenesis, diffuse bone metastatic disease, lymphoma and leukemia (11,(24)(25)(26)(27)(28)(29)(30). Other pathological conditions, like infection or metabolic stress, can also promote EMH.…”

Section: Anatomical Sites Of Emhmentioning

confidence: 99%

“…Recently, a strong association between leukocytosis and CVDs has been demonstrated, thus highlighting innate immunity as a hallmark in the onset and progression of these pathologies (29,71,73). While inflammation associated with atherosclerosis may contribute to this relationship, there is also evidence that leukocytosis directly increases atherosclerosis and thrombosis (26,27,70,74,75). The numerous risk factors for CVDs, including obesity, smoking, sedentary lifestyles and metabolic syndrome (which in turn includes individual components, such as dyslipemia and low HDL), are associated with leukocytosis (42,76).…”

Section: Splenic Extramedullary Hematopoiesis and Atherosclerosis: Thmentioning

confidence: 99%

“…These cells show enhanced expression of Abca1, Abcg1 and Apoe, all of them essential cholesterol-efflux genes. Mice with defects in cholesterol flow pathways (deficiencies of ABCA1 and ABCG1 cassette transporters) show a dramatic increase in HSPCs and EMH (25,27,32,83,96). This favors the tendency of hematopoietic lineages' differentiation towards granulocytes, instead to macrophages in the BM, leading to the deterioration of osteoblasts and to the decrease in the production of CXCL12 (SDF-1) by mesenchymal progenitors.…”

Section: Contribution Of Splenic Neutrophilia and Monocytosis To Athementioning

confidence: 99%

“…Not only has systemic hypercholesterolemia been associated with monocytosis, but also with severe neutrophilia as well (27,97). Current evidence also suggests that neutrophilia may promote early lesion development.…”

Section: Hypercholesterolemia and Splenic Emh In Atherosclerosismentioning

confidence: 99%

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Contribution of Extramedullary Hematopoiesis to Atherosclerosis. The Spleen as a Neglected Hub of Inflammatory Cells

et al. 2020

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Cardiovascular diseases (CVDs) incidence is becoming higher. This fact is promoted by metabolic disorders such as obesity, and aging. Atherosclerosis is the underlying cause of most of these pathologies. It is a chronic inflammatory disease that begins with the progressive accumulation of lipids and fibrotic materials in the blood-vessel wall, which leads to massive leukocyte recruitment. Rupture of the fibrous cap of the atherogenic cusps is responsible for tissue ischemic events, among them myocardial infarction. Extramedullary hematopoiesis (EMH), or blood cell production outside the bone marrow (BM), occurs when the normal production of these cells is impaired (chronic hematological and genetic disorders, leukemia, etc.) or is altered by metabolic disorders, such as hypercholesterolemia, or after myocardial infarction. Recent studies indicate that the main EMH tissues (spleen, liver, adipose and lymph nodes) complement the hematopoietic function of the BM, producing circulating inflammatory cells that infiltrate into the atheroma. Indeed, the spleen, which is a secondary lymphopoietic organ with high metabolic activity, contains a reservoir of myeloid progenitors and monocytes, constituting an important source of inflammatory cells to the atherosclerotic lesion. Furthermore, the spleen also plays an important role in lipid homeostasis and immunecell selection. Interestingly, clinical evidence from splenectomized subjects shows that they are more susceptible to developing pathologies, such as dyslipidemia and atherosclerosis due to the loss of immune selection. Although CVDs represent the leading cause of death worldwide, the mechanisms involving the spleenatherosclerosis-heart axis cross-talk remain poorly characterized.

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Section: Contribution Of Splenic Neutrophilia and Monocytosis To Athementioning

confidence: 89%

Section: Anatomical Sites Of Emhmentioning

confidence: 99%

Section: Splenic Extramedullary Hematopoiesis and Atherosclerosis: Thmentioning

confidence: 99%

Section: Contribution Of Splenic Neutrophilia and Monocytosis To Athementioning

confidence: 99%

Section: Hypercholesterolemia and Splenic Emh In Atherosclerosismentioning

confidence: 99%

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Contribution of Extramedullary Hematopoiesis to Atherosclerosis. The Spleen as a Neglected Hub of Inflammatory Cells

et al. 2020

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Mulberry extract upregulates cholesterol efflux and inhibits p38 MAPK‐NLRP3‐mediated inflammation in foam cells

Liu

Wang

Yang

et al. 2023

Food Science & Nutrition

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The accumulation of foam cells in arterial intima and the accompanied chronic inflammation are considered major causes of neoatherosclerosis and restenosis. However, both the underlying mechanism and effective treatment for the disease are yet to be uncovered. In this study, we combined transcriptome profiling of restenosis artery tissue and bioinformatic analysis to reveal that NLRP3 inflammasome is markedly upregulated in restenosis and that several restenosis‐related DEGs are also targets of mulberry extract, a natural dietary supplement used in traditional Chinese medicine. We demonstrated that mulberry extract suppresses the formation of ox‐LDL‐induced foam cells, possibly by upregulating the cholesterol efflux genes ABCA1 and ABCG1 to inhibit intracellular lipid accumulation. In addition, mulberry extract dampens NLRP3 inflammasome activation by stressing the MAPK signaling pathway. These findings unveil the therapeutic value of mulberry extract in neoatherosclerosis and restenosis treatment by regulating lipid metabolism and inflammatory response of foam cells.

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Uncurtaining the pivotal role of ABC transporters in diabetes mellitus

Behl

Sehgal

Grover³

et al. 2021

Environ Sci Pollut Res

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ABC Transporters, Cholesterol Efflux, and Implications for Cardiovascular Diseases

Cited by 51 publications

References 125 publications

Contribution of Extramedullary Hematopoiesis to Atherosclerosis. The Spleen as a Neglected Hub of Inflammatory Cells

Contribution of Extramedullary Hematopoiesis to Atherosclerosis. The Spleen as a Neglected Hub of Inflammatory Cells

Mulberry extract upregulates cholesterol efflux and inhibits p38 MAPK‐NLRP3‐mediated inflammation in foam cells

Uncurtaining the pivotal role of ABC transporters in diabetes mellitus

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