Activin a inhibits foam cell formation and up-regulates ABCA1 and ABCG1 expression through Alk4-Smad signaling pathway in RAW 264.7 macrophages

Wang, Hao; Zhang, Peng; Chen, Xiahuan; Liu, Wenwen; Fu, Zhanli; Liu, Meilin

doi:10.1016/j.steroids.2021.108887

Cited by 4 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We confirmed TBG-driven Activin A mRNA expression in HepG2 cells and protein in the media, as well as induction of Smad2/3 phosphorylation that was blocked by FST-315, the circulating isoform of FST (Figure S2A). Similar to recombinant Activin A protein, 25,26 Activin A from HepG2 conditioned media also reduced oxLDL uptake by peritoneal macrophages in vitro (Figure 2A and 2B). Thus, the AAV8-TBG-Activin A vector effectively induced Activin A expression and functional protein secretion.…”

Section: Resultsmentioning

confidence: 77%

“…We confirmed TBG-driven Activin A mRNA expression in HepG2 cells and protein in the media, as well as induction of Smad2/3 phosphorylation that was blocked by FST-315, the circulating isoform of FST (Figure S2A). Similar to recombinant Activin A protein, 25,26 Activin A from shows the Activin A but not FST mRNA decreases in the aorta and liver in LDLR −/− mice fed the WD for 12 weeks compared with SD. N=3 mice.…”

Section: Activin a Protects Against Atherosclerosis In Vivomentioning

confidence: 89%

“…On the other hand, in vitro studies demonstrate that Activin A inhibits foam cell formation in Thp1 and Raw 264.7 macrophages, 23,24 thought to model an early step in atherogenesis, while FST promotes foam cell formation in Thp1 macrophages. 25,26 Exogenous Activin A attenuates inflammation in the peripheral blood mononuclear cells from angina patients compared with healthy controls in vitro [20][21][22] and reduces neointimal hyperplasia in a femoral artery cuff murine model in vivo. 27 These studies suggest Activin A may be antiatherogenic and focus on its role in vessel wall constituents.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic Pathways, Inflammation, and Atherosclerosis

Liu

Hastings

Kitchen

et al. 2023

ATVB

View full text Add to dashboard Cite

BACKGROUND: Atherosclerosis is an inflammatory vascular disease marked by hyperlipidemia and hematopoietic stem cell expansion. Activin A, a member of the Activin/GDF/TGFβ/BMP family is broadly expressed and increases in human atherosclerosis, but its functional effects in vivo in this context remain unclear. METHODS: We studied LDLR − /− mice on a Western diet for 12 weeks and used adeno-associated viral vectors with a liver-specific TBG (thyroxine-binding globulin) promoter to express Activin A or GFP (control). Atherosclerotic lesions were analyzed by oil red staining. Blood lipid profiling was performed by high-performance liquid chromatography, and immune cells were evaluated by flow cytometry. Liver RNA-sequencing was performed to explore the underlying mechanisms. RESULTS: Activin A expression decreased in both livers and aortae from LDLR − /− mice fed a Western diet compared with standard laboratory diet. Adenoassociated virus-TBG-Activin A increased Activin A hepatic expression ≈10-fold at 12 weeks; P <0.0001) and circulating Activin A levels ≈2000 pg/ml versus ≈50 pg/ml; P <0.001, compared with controls). Hepatic Activin A expression decreased plasma total and LDL (low-density lipoprotein) cholesterol ≈60% and ≈40%, respectively), reduced inflammatory cells in aortae and proliferating hematopoietic stem cells in bone marrow, and reduced atherosclerotic lesion and necrotic core area in aortae. Activin A also attenuated liver steatosis and expression of the lipogenesis genes, Srebp1 and Srebp2. RNA sequencing revealed Activin A not only blocked expression of genes involved in hepatic de novo lipogenesis but also fatty acid uptake and liver inflammation. In addition, Activin A expressed in the liver also reduced white fat tissue accumulation, decreased adipocyte size, and improved glucose tolerance. CONCLUSIONS: Our studies reveal hepatic Activin A expression reduces inflammation, hematopoietic stem cell expansion, liver steatosis, circulating cholesterol, and fat accumulation, which likely all contribute to the observed protection against atherosclerosis. The reduced Activin A observed in LDLR −/− mice on a Western diet seems maladaptive and deleterious for atherogenesis.

show abstract

Section: Resultsmentioning

confidence: 77%

“…We confirmed TBG-driven Activin A mRNA expression in HepG2 cells and protein in the media, as well as induction of Smad2/3 phosphorylation that was blocked by FST-315, the circulating isoform of FST (Figure S2A). Similar to recombinant Activin A protein, 25,26 Activin A from shows the Activin A but not FST mRNA decreases in the aorta and liver in LDLR −/− mice fed the WD for 12 weeks compared with SD. N=3 mice.…”

Section: Activin a Protects Against Atherosclerosis In Vivomentioning

confidence: 89%

mentioning

confidence: 99%

See 1 more Smart Citation

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic Pathways, Inflammation, and Atherosclerosis

Liu

Hastings

Kitchen

et al. 2023

ATVB

View full text Add to dashboard Cite

show abstract

“…We confirmed TBG-driven Activin A mRNA expression in HepG2 cells and protein in the media, as well as induction of Smad2/3 phosphorylation that was blocked by FST-315, the circulating isoform of FST (Figure S2A). Similar to recombinant Activin A protein 24,25 , Activin A from HepG2 conditioned media also reduced oxLDL uptake by peritoneal macrophages in vitro (Figure 2A-2B). Thus, the AAV8-TBG-Activin A vector effectively induces Activin A expression and functional protein secretion.…”

Section: Activin a Protects Against Atherosclerosis In Vivomentioning

confidence: 81%

“…These observations suggest Activin A could contribute to atherosclerosis progression. On the other hand, in vitro studies demonstrate that Activin A inhibits foam cell formation in Thp1 and Raw 264.7 macrophages 22, 23 , thought to model an early step in atherogenesis, while FST promotes foam cell formation in Thp1 macrophages 24, 25 . Exogenous Activin A has also been reported to reduce neointimal hyperplasia in a femoral artery cuff murine model in vivo 26 .…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic pathways, Inflammation, and Atherosclerosis

Liu

Hastings

Kitchen

et al. 2022

Preprint

View full text Add to dashboard Cite

BACKGROUNDAtherosclerosis is an inflammatory vascular disease marked by hyperlipidemia and hematopoietic stem cell (HSC) expansion. Activin A, a member of the Activin/GDF/TGFβ/BMP family is broadly expressed and increases in human atherosclerosis, but its functional effects in vivo in this context remain unclear.METHODSWe studied LDLR-/- mice on a Western diet for 12 weeks and used adeno-associated viral vectors with a liver-specific thyroxine binding globulin (TBG) promoter to express Activin A or GFP (control). Atherosclerotic lesions were analyzed by oil red staining. Blood lipid profiling was performed by HPLC (High Performance Liquid Chromatography), and immune cells were evaluated by flow cytometry. Liver RNA-sequencing was performed to explore the underlying mechanisms.RESULTSActivin A expression decreased in both livers and aortae from LDLR-/- mice fed a Western diet compared with chow. AAV-TBG-Activin A increased Activin A hepatic expression (∼10-fold at 12-weeks, p<0.0001) and circulating Activin A levels (∼2000pg/ml vs ∼50pg/ml, p<0.001, compared with controls). Hepatic Activin A expression decreased plasma total and low-density lipoprotein (LDL) cholesterol (∼60% and ∼40%, respectively), reduced inflammatory cells in aortae and proliferating hematopoietic stem cells (HSC) in bone marrow, and reduced atherosclerotic lesion area in the aortic arch by ∼60%. Activin A also attenuated liver steatosis and expression of the lipogenesis genes, Srebp1 and Srebp2. RNA sequencing revealed Activin A not only blocked expression of genes involved in hepatic de novo lipogenesis but also fatty acid uptake, and liver inflammation. In addition, Activin A expressed in the liver also reduced white fat tissue accumulation, decreased adipocyte size, and improved glucose tolerance.CONCLUSIONSOur studies reveal hepatic Activin A expression reduces inflammation, HSC expansion, liver steatosis, circulating cholesterol, and fat accumulation, which likely all contribute to the observed protection against atherosclerosis. The reduced Activin A observed in LDLR-/- mice on a Western diet appears maladaptive and deleterious for atherogenesis.

show abstract

Identification, expression and functional analysis of activin type I receptor in common Chinese Cuttlefish, Sepiella japonica

Liu

Zhao

Lü

et al. 2022

Animal Reproduction Science

View full text Add to dashboard Cite

Activin a inhibits foam cell formation and up-regulates ABCA1 and ABCG1 expression through Alk4-Smad signaling pathway in RAW 264.7 macrophages

Cited by 4 publications

References 51 publications

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic Pathways, Inflammation, and Atherosclerosis

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic Pathways, Inflammation, and Atherosclerosis

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic pathways, Inflammation, and Atherosclerosis

Identification, expression and functional analysis of activin type I receptor in common Chinese Cuttlefish, Sepiella japonica

Contact Info

Product

Resources

About