ApoA-I/A-II-HDL positively associates with apoB-lipoproteins as a potential atherogenic indicator

Kido, Takamasa; Kondo, Kazuo; Kurata, Hiroyuki; Fujiwara, Yoko; Urata, Takeyoshi; Itakura, Hiroshige; Yokoyama, Shinji

doi:10.1186/s12944-017-0619-y

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…Lipoproteins (Lps) containing apoA-I alone (LpA-I) and Lps containing both apoA-I and apoA-II (LpA-I:A-II) are structurally and metabolically different [ 83 ]. LpA-I:A-II is more pro-atherogenic than LpA-I [ 84 ]. Overall, an increase in the apoA-II content impaired the HDL quality and functionality, regardless of the elevation of the HDL-C level.…”

Section: Hdl Qualitymentioning

confidence: 99%

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Cho

2022

IJMS

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The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one’s lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. Nevertheless, high HDL quantity is not always accompanied by good HDL quality or functionality. The HDL quality concerns the morphology of the HDL, such as particle size, shape, and number. The HDL quality also depends on the composition of the HDL, such as apolipoproteins (apoA-I, apoA-II, apoC-III, serum amyloid A, and α-synuclein), cholesterol, and triglyceride. The HDL quality is also associated with the extent of HDL modification, such as glycation and oxidation, resulting in the multimerization of apoA-I, and the aggregation leads to amyloidogenesis. The HDL quality frequently determines the HDL functionality, which depends on the attached antioxidant enzyme activity, such as the paraoxonase and cholesterol efflux activity. Conventional HDL functionality is regression, the removal of cholesterol from atherosclerotic lesions, and the removal of oxidized species in low-density lipoproteins (LDL). Recently, HDL functionality was reported to expand the removal of β-amyloid plaque and inhibit α-synuclein aggregation in the brain to attenuate Alzheimer’s disease and Parkinson’s disease, respectively. More recently, HDL functionality has been associated with the susceptibility and recovery ability of coronavirus disease 2019 (COVID-19) by inhibiting the activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The appearance of dysfunctional HDL is frequently associated with many acute infectious diseases and chronic aging-related diseases. An HDL can be a suitable biomarker to diagnose many diseases and their progression by monitoring the changes in its quantity and quality in terms of the antioxidant and anti-inflammatory abilities. An HDL can be a protein drug used for the removal of plaque and as a delivery vehicle for non-soluble drugs and genes. A dysfunctional HDL has poor HDL quality, such as a lower apoA-I content, lower antioxidant ability, smaller size, and ambiguous shape. The current review analyzes the recent advances in HDL quantity, quality, and functionality, depending on the health and disease state during one’s lifetime.

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Section: Hdl Qualitymentioning

confidence: 99%

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Cho

2022

IJMS

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“…Although apoA-II is the second most abundant protein constituent of HDL, apoA-II is still an enigmatic apolipoprotein. HDL containing apoA-I alone (LpA-I) and HDL containing apoA-I and apoA-II (LpA-I:A-II) were distinctly different, both structurally and metabolically [ 31 ]; LpA-I:A-II is more pro-atherogenic [ 32 ]. LpA-I is more cardioprotective in patients with coronary artery disease than LpA-I-I:A-II.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of High-Density Lipoprotein (HDL) Quantity and Quality by Regular and Habitual Exercise in Middle-Aged Women with Improvements in Lipid and Apolipoprotein Profiles: Larger Particle Size and Higher Antioxidant Ability of HDL

Cho

Nam²,

Kang³

et al. 2023

IJMS

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Regular exercise, especially aerobic exercise, is beneficial for increasing serum high-density lipoprotein-cholesterol (HDL-C) levels in the general population. In addition to the HDL-C quantity, exercise enhances HDL functionality, antioxidants, and cholesterol efflux. On the other hand, the optimal intensity and frequency of exercise to increase HDL quantity and enhance HDL quality in middle-aged women need to be determined. The current study was designed to compare the changes in HDL quantity and quality among middle-aged women depending on exercise intensity, frequency, and duration; participants were divided into a sedentary group (group 1), a middle-intensity group (group 2), and a high-intensity group (group 3). There were no differences in anthropometric parameters among the groups, including blood pressure, muscle mass, and handgrip strength. Although there was no difference in serum total cholesterol (TC) among the groups, the serum HDL-C and apolipoprotein (apo)A-I levels remarkably increased to 17% and 12%, respectively, in group 3. Serum low-density lipoprotein-cholesterol (LDL-C), glucose, triglyceride, and the apo-B/apoA-I ratio were remarkably decreased in the exercise groups depending on the exercise intensity; group 3 showed 13%, 10%, and 45% lower LDL-C, glucose, and triglyceride (TG), respectively, than group 1. The hepatic and muscle damage parameter, aspartate aminotransferase (AST), was significantly decreased in the exercise groups, but high-sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) were similar in the three groups. In LDL, the particle size was increased 1.5-fold (p < 0.001), and the oxidation extent was decreased by 40% with a 23% lower TG content in group 3 than in group 1. In the exercise groups (groups 2 and 3), LDL showed the slowest electromobility with a distinct band intensity compared to the sedentary group (group 1). In HDL2, the particle size was 2.1-fold increased (p < 0.001) in the exercise group (group 3) with a 1.5-fold increase in TC content compared to that in group 1, as well as significantly enhanced antioxidant abilities, paraoxonase (PON) activity, and ferric ion reduction ability (FRA). In HDL3, the particle size was increased 1.2-fold with a 45% reduction in TG in group 3 compared to group 1. With increasing exercise intensity, apoA-I expression was increased in HDL2 and HDL3, and PON activity and FRA were enhanced (p < 0.001). In conclusion, regular exercise in middle-aged women is associated with the elevation of serum HDL-C and apoA-I with the enhancement of HDL quality and functionality and an increase in the TC content, particle size, and antioxidant abilities. With the reduction in TG and oxidized products in LDL and HDL, lipoproteins could have more anti-atherogenic properties through regular exercise in an intensity-dependent manner.

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“…The ratio of apoA-II/apoB was identified as a better prognostic parameter for lipoprotein-associated risk of postoperative mortality, as compared with the established lipid-risk parameters in patients with high-grade carotid stenosis; therefore, apoA-II/apoB ratio was proposed as an additional risk-prediction tool [ 91 ]. Although structural and functional differences between HDL particles with and without apoA-II (LpA-I: A-II and LpA-I) have not been fully distinguished, LpA-I particles are considered to be more responsible for the anti-atherogenic properties of HDL and LpA-I: A-II particles represents rather an atherogenic indicator [ 92 ].…”

Section: Role Of Apoa-ii In Various Pathologiesmentioning

confidence: 99%

Apolipoprotein A-II, a Player in Multiple Processes and Diseases

et al. 2022

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Apolipoprotein A-II (apoA-II) is the second most abundant apolipoprotein in high-density lipoprotein (HDL) particles, playing an important role in lipid metabolism. Human and murine apoA-II proteins have dissimilar properties, partially because human apoA-II is dimeric whereas the murine homolog is a monomer, suggesting that the role of apoA-II may be quite different in humans and mice. As a component of HDL, apoA-II influences lipid metabolism, being directly or indirectly involved in vascular diseases. Clinical and epidemiological studies resulted in conflicting findings regarding the proatherogenic or atheroprotective role of apoA-II. Human apoA-II deficiency has little influence on lipoprotein levels with no obvious clinical consequences, while murine apoA-II deficiency causes HDL deficit in mice. In humans, an increased plasma apoA-II concentration causes hypertriglyceridemia and lowers HDL levels. This dyslipidemia leads to glucose intolerance, and the ensuing high blood glucose enhances apoA-II transcription, generating a vicious circle that may cause type 2 diabetes (T2D). ApoA-II is also used as a biomarker in various diseases, such as pancreatic cancer. Herein, we provide a review of the most recent findings regarding the roles of apoA-II and its functions in various physiological processes and disease states, such as cardiovascular disease, cancer, amyloidosis, hepatitis, insulin resistance, obesity, and T2D.

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ApoA-I/A-II-HDL positively associates with apoB-lipoproteins as a potential atherogenic indicator

Cited by 8 publications

References 32 publications

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Enhancement of High-Density Lipoprotein (HDL) Quantity and Quality by Regular and Habitual Exercise in Middle-Aged Women with Improvements in Lipid and Apolipoprotein Profiles: Larger Particle Size and Higher Antioxidant Ability of HDL

Apolipoprotein A-II, a Player in Multiple Processes and Diseases

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