APOA1: a Protein with Multiple Therapeutic Functions

Cochran, Blake J.; Ong, Kwok Leung; Manandhar, Bikash; Rye, Kerry‐Anne

doi:10.1007/s11883-021-00906-7

Cited by 95 publications

(71 citation statements)

References 98 publications

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“… 6 , 7 In addition to its cardiovascular protective properties, APOA1 has multifunctional roles in immunity and inflammation. 8 Increasing evidence strongly supports the assertion that APOA1 is a “negative” acute-phase protein, and acts as a natural inhibitory factor in plasma during autoimmune diseases (AD). 9 Moreover, APOA1 has been reported to be a predictive plasma biomarker for a good response to biologics.…”

mentioning

confidence: 94%

Apolipoprotein A1 Modulates Teff/Treg Balance Through Scavenger Receptor Class B Type I-Dependent Mechanisms in Experimental Autoimmune Uveitis

Huang

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Experimental autoimmune uveitis (EAU) is a representative animal model of human uveitis. In this study, we investigated whether apolipoprotein A1 (APOA1) can alleviate EAU and explored its underlying mechanism. Methods Mice were immunized with interphotoreceptor retinoid-binding protein 1-20 and treated with APOA1 or vehicle. The retinas, draining lymph nodes (DLNs), and spleens were analyzed. Isolated T cells were used for proliferation, differentiation, and function assays in vitro. Selective inhibitors and pathway agonists were used to study signaling pathways. The effect of APOA1 on peripheral blood mononuclear cells (PBMCs) from uveitis patients was also examined. Results Administration of APOA1 ameliorated EAU. APOA1 suppressed pathogenic CD4+ T cell expansion in DLNs and spleen, and decreased the infiltration of effector T (Teff) cells into retina. APOA1 also inhibited T cell proliferation and T helper 1 cell differentiation in vitro and promoted regulatory T (Treg) cell differentiation. APOA1 restricted inflammatory cytokine production from lipopolysaccharide-stimulated PBMCs. Mechanistic studies revealed that the effect of APOA1 was mediated by scavenger receptor class B type I (SR-BI) and downstream signals including phosphatidylinositol 3-kinase/Protein kinase B (PKB, or Akt), p38 mitogen-activated protein kinase, and nuclear factor–κB. Conclusions APOA1 ameliorates EAU by regulating the Teff/Treg partially through SR-BI. Our results suggest that APOA1 can be a therapeutic alternative for autoimmune uveitis.

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confidence: 94%

Apolipoprotein A1 Modulates Teff/Treg Balance Through Scavenger Receptor Class B Type I-Dependent Mechanisms in Experimental Autoimmune Uveitis

Huang

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…ApoA2 may serve as a potential therapeutic target for atherosclerosis (29). ApoA1 has multiple beneficial functions, such as cardio protective, potent antioxidant and anti-inflammatory (30)(31)(32)(33). In fat globule membrane (MFGM) of DM, ApoA1 was upregulated in colostrum compared with mature milk (34).…”

Section: Discussionmentioning

confidence: 99%

Comparative Whey Proteome Profiling of Donkey Milk With Human and Cow Milk

Zhang

Jiang²,

Ji³

et al. 2022

Front. Nutr.

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Donkey milk (DM), similar to human milk (HM) in chemical composition, has been suggested as the best potential hypoallergenic replacement diet for babies suffering from Cow milk (CM) protein allergy. In order to better understand DM protein, many studies based on proteomic have been performed. In this study, the label-free quantitative proteomic approach was conducted to quantitatively identify the differentially expressed whey proteins (DEPs) in DM vs. HM group and DM vs. CM group. In total, 241 and 365 DEPs were found in these two groups, respectively. Bioinformatics analysis of DEPs showed that the majority of DEPs participated in the lipoprotein metabolic process, regulation of cytokine production, chemical homeostasis, and catabolic process. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways analysis found that these DEPs mainly participated in an antigen processing, complement, and coagulation cascades. These results may provide valuable information in the composition of milk whey proteins in DM, HM, and CM, especially for low abundant components, and expand our knowledge of different biological functions between DM and HM or CM.

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“…In line with this, the Cys82 polymorphism reached nominal significance in the latest GWAS for cardiovascular outcomes (β = 0.057; P = 2.2E-3) [ 53 ] (see Supplementary Table S2 [ 44 ]) and is linked to increased atherosclerosis ( P = 4.18E-6), and peripheral artery disease in FINNGEN ( P = 2.73E-5/unpublished data, URL: https://r5.finngen.fi/variant/17-43848758-C-T ). Furthermore, we found the Arg82 polymorphism to be linked to decreased ApoA1 level—a protein component of HDL involved in lipid metabolism (see Table 2 ), which has previously been linked to cardioprotective properties [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

The Arg82Cys Polymorphism of the Protein Nepmucin Implies a Role in HDL Metabolism

Metz

Krarup

Bryrup

et al. 2022

Journal of the Endocrine Society

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Background Blood lipid levels are linked to the risk of cardiovascular disease and regulated by genetic factors. A low-frequency polymorphism Arg82Cys (rs72836561) in the membrane protein nepmucin, encoded by CD300LG, is associated with lower fasting concentration of HDL-cholesterol and higher fasting triglycerides. However, whether the variant is linked to postprandial lipids and glycemic status remains elusive. Here, we augment the genetic effect of Arg82Cys on fasting plasma concentrations of HDL subclasses, postprandial lipemia after a standardized high-fat meal, and glycemic status to further untangle its role in HDL-metabolism. Methods Therefore, we elucidated fasting associations with HDL subclasses in a population-based cohort study (Oxford Biobank, OBB), including 4,522 healthy men and women. We investigated fasting and postprandial consequences on HDL metabolism in recall-by-genotype (RbG) studies (fasting: 20 carrier/20 non-carrier; postprandial: 7 carrier/17 non-carrier), and shed light on the synergistic interaction with glycemic status. Results A lower fasting plasma concentration of cholesterol in large HDL particles was found in healthy male carriers of the Cys82 polymorphism compared to non-carriers, both in the OBB (P=0.004) and RbG studies (P=0.005). Additionally, the Cys82 polymorphism was associated with low fasting plasma concentrations of ApoA1 (P=0.008) in the OBB cohort. On the contrary, we did not find differences in postprandial lipemia or 2 hour plasma glucose levels. Conclusion Taken together, our results indicate an association between the Arg82Cys variant and a lower concentration of HDL particles and HDL cholesterol, especially in larger HDL subclasses, suggesting a link between nepmucin and HDL cholesterol metabolism or maturation.

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APOA1: a Protein with Multiple Therapeutic Functions

Cited by 95 publications

References 98 publications

Apolipoprotein A1 Modulates Teff/Treg Balance Through Scavenger Receptor Class B Type I-Dependent Mechanisms in Experimental Autoimmune Uveitis

Apolipoprotein A1 Modulates Teff/Treg Balance Through Scavenger Receptor Class B Type I-Dependent Mechanisms in Experimental Autoimmune Uveitis

Comparative Whey Proteome Profiling of Donkey Milk With Human and Cow Milk

The Arg82Cys Polymorphism of the Protein Nepmucin Implies a Role in HDL Metabolism

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