Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics

Bhale, Aishwarya; Venkataraman, Krishnan

doi:10.1016/j.biopha.2022.113634

Cited by 47 publications

(27 citation statements)

References 167 publications

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“…As a member of the apolipoprotein family, Apolipoprotein A-I (APOA1) is a vital component of high-density lipoprotein (HDL) particles and plays a crucial role in reverse cholesterol transport . It is reported that HDL has a curb on lysosomal activity in mice macrophages, in accord with the finding of high levels of expressed ApoA1 along with a reduced involvement of lysosomal activity in mouse models, implying that decreased expression of ApoA1 may be linked to promoted lysosomal metabolism disorders in MPS I patients.…”

Section: Discussionmentioning

confidence: 88%

Co-Analysis of Serum and Urine Differentially Expressed Proteins in Mucopolysaccharidosis Type I

Liu,

Wan,

et al. 2024

J. Proteome Res.

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Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by the deficiency of the enzyme α-L-iduronidase (IDUA), typically leading to devastating secondary pathophysiological cascades. Due to the irreversible nature of the disease's progression, early diagnosis and interventional treatment has become particularly crucial. Considering the fact that serum and urine are the most commonly used specimens in clinical practice for detection, we conducted an analysis to identify the differential protein profile in the serum and urine of MPS I patients using the tandem mass tag (TMT) technique. A total of 182 differentially expressed proteins (DEPs) were detected in serum, among which 9 showed significant differences as confirmed by parallel reaction monitoring (PRM) analysis. The proteins APOA1 and LGFBP3 were downregulated in serum, while the expression levels of ALDOB, CD163, CRTAC1, DPP4, LAMP2, SHBG, and SPP2 exhibited an increase. In further exploratory studies of urinary proteomics, 32 identified DEPs were consistent with the discovered findings in serum tests, specifically displaying a high diagnostic area under the curve (AUC) value. Thus, our study demonstrates the value of serum-urine integrated proteomic analysis in evaluating the clinical course of MPS I and other potential metabolic disorders, shedding light on the importance of early detection and intervention in these conditions.

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Section: Discussionmentioning

confidence: 88%

Co-Analysis of Serum and Urine Differentially Expressed Proteins in Mucopolysaccharidosis Type I

Liu,

Wan,

et al. 2024

J. Proteome Res.

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“…In addition, in the subgroup of disease types, we found that selenium supplementation increased HDL-C levels more significantly in participants with cardiovascular disease, followed by those with diabetes mellitus. HDL-C is essential for reverse cholesterol transport and has antiinflammatory, anti-atherogenic, and anti-thrombotic effects [76]. The interaction of these properties contributes to the cardioprotective properties of HDL-C.…”

Section: Discussionmentioning

confidence: 99%

Potential Benefits of Selenium Supplementation in Reducing Insulin Resistance in Patients with Cardiometabolic Diseases: A Systematic Review and Meta-Analysis

et al. 2022

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Background: Selenium is a trace element that has been reported to be effective in regulating glucose and lipid metabolism. However, there is conflicting evidence from different clinical trials of selenium supplementation in treating cardiometabolic diseases (CMDs). Objective: This meta-analysis aimed to identify the effects of selenium supplementation on insulin resistance, glucose homeostasis, and lipid profiles in patients with CMDs. Methods: Randomized controlled trials (RCTs) of selenium supplementation for treating CMDs were screened in five electronic databases. Insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), and glycosylated hemoglobin A1C (HbA1c) were defined as the primary outcome markers, and lipid profiles were considered the secondary outcome markers. Results: Ten studies involving 526 participants were included in the meta-analysis. The results suggested that selenium supplementation significantly reduced serum insulin levels (standardized men difference [SMD]: −0.53; 95% confidence interval [CI] [−0.84, −0.21], p = 0.001, I2 = 68%) and HOMA-IR (SMD: −0.50, 95% CI [−0.86, −0.14], p = 0.006, I2 = 75%) and increased high-density lipoprotein cholesterol (HDL-C) levels (SMD: 0.97; 95% CI [0.26, 1.68], p = 0.007, I2 = 92%), but had no significant effect on FPG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). Conclusion: Current evidence supports the beneficial effects of selenium supplementation on reducing insulin levels, HOMA-IR, and increasing HDL-C levels. Selenium supplementation may be an effective strategy for reducing insulin resistance in patients with CMDs. However, more high-quality clinical studies are needed to improve the certainty of our estimates.

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“…Interestingly, the same authors also found apoA1 overexpression in the retina of diabetic donors and hypothesized that the increased production of retinal apoA1 was a protective compensatory mechanism against DR due to its function of transport of lipids within the retina [25] . ApoA1 and its mimic peptides are reported to have antiinflammatory and antioxidant functions and to be involved in the intraretinal reverse transport of lipids [6][7][8] . As demonstrated, apoA1-mimic peptides inhibited neovascularization in mouse ovarian cancer models, which was associated with the inhibited phosphorylation of ERK and AKT [9] .…”

Section: Mek/erk Signaling Pathways Mediate Plgf Secretion Migration ...mentioning

confidence: 99%

“…ApoA1 is the major apoA protein and accounts for approximately 70% of the total protein mass of high-density lipoproteins [5] . ApoA1 has anti-inflammatory, antioxidant and intraretinal reverse transport effects on lipids [6][7][8] . The antiangiogenic properties of apoA1-mimic peptides in tumors have been reported [9] .…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein A1 suppresses the hypoxia-induced angiogenesis of human retinal endothelial cells by targeting PlGF

Hu¹,

Su²,

Yu³

et al. 2023

Int J Ophthalmol

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AIM: To investigate the anti-angiogenic effect of apolipoprotein A1 (apoA1) on primary human retinal vascular endothelial cells (HRECs) and explore the possible mechanism. METHODS: The primary HRECs were transfected with apoA1-GFP recombinant lentiviral and were compared with cells undergoing transfection with empty lentiviral vectors. Hypoxia chambers were used to simulate the anoxic environment of cells under pathological condition. The concentrations of secreted vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were measured by enzyme-linked immunosorbent assay (ELISA). Cell migration ability was detected by wound healing assay. The sprouting of HRECs was determined by tube formation assay. The protein levels of extracellular signal regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were measured by Western blot. RESULTS: Overexpressed apoA1 in hypoxia-induced HRECs significantly suppressed PlGF (0.67±0.10 folds, P=0.007). Overexpressed apoA1 also attenuated hypoxia-induced cell migration (0.32±0.11 folds, P<0.0001), tube formation (0.66±0.01 folds, P<0.0001) and the phosphorylation levels of ERK (0.6±0.11 folds, P=0.025). Pretreatment of mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) further reduced the PlGF and angiogenesis in hypoxia-induced HRECs. CONCLUSION: ApoA1 inhibits the angiogenesis at least in part by inactivating ERK1/2 in hypoxia-induced HRECs. Moreover, apoA1 suppresses the PlGF expression, which selectively associated with pathological angiogenesis.

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Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics

Cited by 47 publications

References 167 publications

Co-Analysis of Serum and Urine Differentially Expressed Proteins in Mucopolysaccharidosis Type I

Co-Analysis of Serum and Urine Differentially Expressed Proteins in Mucopolysaccharidosis Type I

Potential Benefits of Selenium Supplementation in Reducing Insulin Resistance in Patients with Cardiometabolic Diseases: A Systematic Review and Meta-Analysis

Apolipoprotein A1 suppresses the hypoxia-induced angiogenesis of human retinal endothelial cells by targeting PlGF

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