The pleiotropic effects of high-density lipoproteins and apolipoprotein A-I

Thomas, Shane R.; Zhang, Yunjia; Rye, Kerry‐Anne

doi:10.1016/j.beem.2022.101689

Cited by 4 publications

(4 citation statements)

References 141 publications

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“…The HDL heterogeneity is a consequence of the maturation process of HDL metabolism, which includes the concerted action of apolipoproteins, transporters, enzymes, and receptors [20]. The present results show that HDL size gradually decreased from normoglycemia to prediabetes and T2D.…”

Section: Discussionsupporting

confidence: 49%

“…Because of their antioxidant, anti-inflammatory, antiapoptotic, antithrombotic, and vasodilatory properties, these lipoproteins are considered atheroprotective. Furthermore, they can also promote cholesterol efflux from the macrophages of the subendothelial region, which prevents atherosclerosis development [20]. Previously, it has been reported that HDL subfractions leading to a smaller size are related to cardiovascular risk conditions, including T2D [21].…”

Section: Introductionmentioning

confidence: 99%

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Adipose tissue dysfunction serum markers are associated with high density lipoprotein size and glycation in the early stages of type 2 diabetes

et al. 2023

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Background High-density lipoproteins (HDLs) have antiatherogenic properties related to their chemical structure. Adipose tissue (AT) influences HDL reverse cholesterol transport and plasma HDL cholesterol levels. However, whether AT dysfunction affects HDL subpopulations and their glycation in early type 2 diabetes (T2D) is still unknown. Objective To investigate the association of inflammation and AT dysfunction serum markers with the size and glycation of HDLs in normoglycemic, prediabetes, and T2D subjects. Methods We assessed HDL particle size and advanced glycation end-product (AGE) content in HDLs isolated from normoglycemic (n = 17), prediabetes (n = 17), and recently T2D-diagnosed (n = 18) subjects. Insulin, adiponectin, and plasminogen activator inhibitor 1 (PAI-1) were determined using the Bio-Rad Multiplex Platform, and free fatty acids (FFAs) and high sensitivity C-reactive protein (hs-CRP) were determined by standard procedures. The AT insulin resistance (ATIR) index and ATIR/adiponectin and adiponectin/leptin ratios were calculated. Results HDL was progressively smaller (nm) and enriched with AGE (mg-BSA-AGE/mg protein) according to the glucose categories: 8.49 and 7.5 in normoglycemic subjects, 8.44 and 12.4 in prediabetic subjects, and 8.32 and 14.3 in T2D subjects (P = 0.033 and P = 0.009 for size and AGE, respectively). In multivariable regression analysis, the ATIR/adiponectin ratio was inversely associated with HDL size (β = -0.257, P = 0.046), and the ATIR ratio was directly associated with HDL glycation (β = 0.387, P = 0.036). In contrast, adiponectin and the adiponectin/leptin ratio were not associated with alterations in HDL particles. Furthermore, HDL size was associated with resistin (β = -0.348, P = 0.007) and PAI-1 (β = -0.324, P = 0.004). HDL and AGE were related to insulin concentrations (β = 0.458, P = 0.015). Analyses were adjusted for age, sex, body mass index, triglycerides, and HDL-cholesterol. Conclusion HDL size was significantly associated with the ATIR/adiponectin ratio and inflammation, whereas glycation was more strongly related to the ATIR index. These findings have important implications for the management and prevention of cardiovascular disease in T2D patients.

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Adipose tissue dysfunction serum markers are associated with high density lipoprotein size and glycation in the early stages of type 2 diabetes

et al. 2023

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“…Subsequently, LCAT combines LpA-II with circulating LpA-I particles to form LpA-I/A-II particles [144]. Unlike ApoA-I, ApoA-II cannot activate LCAT [145,146]. ApoA-II plays a role in HDL maturation and reverse cholesterol efflux and exerts antioxidative properties.…”

Section: Role Of Apoa-ii In Lipid Metabolismmentioning

confidence: 99%

Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling

Reijnders,

van der Laarse,

Ruhaak

et al. 2024

Clin Proteom

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In persons with dyslipidemia, a high residual risk of cardiovascular disease remains despite lipid lowering therapy. Current cardiovascular risk prediction mainly focuses on low-density lipoprotein cholesterol (LDL-c) levels, neglecting other contributing risk factors. Moreover, the efficacy of LDL-c lowering by statins resulting in reduced cardiovascular risk is only partially effective. Secondly, from a metrological viewpoint LDL-c falls short as a reliable measurand. Both direct and calculated LDL-c tests produce inaccurate test results at the low end under aggressive lipid lowering therapy. As LDL-c tests underperform both clinically and metrologically, there is an urging need for molecularly defined biomarkers. Over the years, apolipoproteins have emerged as promising biomarkers in the context of cardiovascular disease as they are the functional workhorses in lipid metabolism. Among these, apolipoprotein B (ApoB), present on all atherogenic lipoprotein particles, has demonstrated to clinically outperform LDL-c. Other apolipoproteins, such as Apo(a) - the characteristic apolipoprotein of the emerging risk factor lipoprotein(a) -, and ApoC-III - an inhibitor of triglyceride-rich lipoprotein clearance -, have attracted attention as well. To support personalized medicine, we need to move to molecularly defined risk markers, like the apolipoproteins. Molecularly defined diagnosis and molecularly targeted therapy require molecularly measured biomarkers. This review provides a summary of the scientific validity and (patho)physiological role of nine serum apolipoproteins, Apo(a), ApoB, ApoC-I, ApoC-II, ApoC-III, ApoE and its phenotypes, ApoA-I, ApoA-II, and ApoA-IV, in lipid metabolism, their association with cardiovascular disease, and their potential as cardiovascular risk markers when measured in a multiplex apolipoprotein panel.

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“…The apolipoprotein A‐I (apoA‐I), the main apolipoprotein constituent of HDL, acquires cholesterol and phospholipids through its interaction with ATP‐binding cassette transporter A1 (ABCA1), leading to the formation of pre‐β HDL particles 23 . These particles gradually accumulate more cholesterol, and further maturation of HDL occurs through binding to ABCG1, generating the spherical HDL particles that predominate in normal human plasma 22 , 24 . Following the esterification of cholesterol by the enzyme lecithin‐cholesterol acyltransferase (LCAT), cholesteryl ester is transferred to the core of the HDL particles, which may undergo clearance by the hepatic scavenger receptor 23 , or be transferred to VLDL/LDL for catabolism via the cholesteryl ester transfer protein (CETP).…”

Section: Hdl Composition Subfractions and Subspeciesmentioning

confidence: 99%

High‐density lipoprotein in diabetes: Structural and functional relevance

Lui,

Tan

2024

J of Diabetes Invest

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Low levels of high‐density lipoprotein‐cholesterol (HDL‐C) is considered a major cardiovascular risk factor. However, recent studies have suggested a more U‐shaped association between HDL‐C and cardiovascular disease. It has been shown that the cardioprotective effect of HDL is related to the functions of HDL particles rather than their cholesterol content. HDL particles are highly heterogeneous and have multiple functions relevant to cardiometabolic conditions including cholesterol efflux capacity, anti‐oxidative, anti‐inflammatory, and vasoactive properties. There are quantitative and qualitative changes in HDL as well as functional abnormalities in both type 1 and type 2 diabetes. Non‐enzymatic glycation, carbamylation, oxidative stress, and systemic inflammation can modify the HDL composition and therefore the functions, especially in situations of poor glycemic control. Studies of HDL proteomics and lipidomics have provided further insights into the structure–function relationship of HDL in diabetes. Interestingly, HDL also has a pleiotropic anti‐diabetic effect, improving glycemic control through improvement in insulin sensitivity and β‐cell function. Given the important role of HDL in cardiometabolic health, HDL‐based therapeutics are being developed to enhance HDL functions rather than to increase HDL‐C levels. Among these, recombinant HDL and small synthetic apolipoprotein A‐I mimetic peptides may hold promise for preventing and treating diabetes and cardiovascular disease.

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The pleiotropic effects of high-density lipoproteins and apolipoprotein A-I

Cited by 4 publications

References 141 publications

Adipose tissue dysfunction serum markers are associated with high density lipoprotein size and glycation in the early stages of type 2 diabetes

Adipose tissue dysfunction serum markers are associated with high density lipoprotein size and glycation in the early stages of type 2 diabetes

Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling

High‐density lipoprotein in diabetes: Structural and functional relevance

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