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Journal of the American Heart... Aug 2023Concern continues about whether the measurement of apolipoprotein B (apoB) is adequately standardized, and therefore, whether apoB should be applied widely in clinical... (Review)
Review
Concern continues about whether the measurement of apolipoprotein B (apoB) is adequately standardized, and therefore, whether apoB should be applied widely in clinical care. This concern is misplaced. Our objective is to explain why and what the term "standardization" means. To produce clinically valid results, a test must accurately, precisely, and selectively measure the marker of interest. That is, it must be standardized. Accuracy refers to how closely the result obtained with 1 method corresponds to the result obtained with the standard method, precision to how reproducible the result is on repeated testing, and selectivity to how susceptible the method is to error by inclusion of other classes of lipoprotein particles. Multiple expert groups have determined that the measurement of apoB is adequately standardized for clinical care, and that apoB can be measured inexpensively, using widely available automated methods, more accurately, precisely, and selectively than low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. ApoB is a standard superior to low-density lipoprotein cholesterol and high-density lipoprotein cholesterol because it is a defined molecule, whereas the cholesterol markers are the mass of cholesterol within lipoprotein particles defined by their density, not by their molecular structure. Nevertheless, the standardization of apoB is being further improved by the application of mass spectrophotometric methods, whereas the limitations in the standardization and, therefore, the accurate, precise, and selective measurement of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol are unlikely to be overcome. We submit that greater accuracy, precision, and selectivity in measurement is a decisive advantage for apoB in the modern era of intensive lipid-lowering therapies.
Topics: Cholesterol, LDL; Cholesterol; Apolipoproteins B; Apolipoprotein B-100; Cholesterol, HDL; Lipoproteins; Apolipoprotein A-I
PubMed: 37489721
DOI: 10.1161/JAHA.123.030405 -
Current Opinion in Cardiology Jan 2024Some experts and consensus groups continue to argue that apolipoprotein B (apoB) should not be introduced broadly into clinical care. But, too often, the present... (Review)
Review
PURPOSE OF REVIEW
Some experts and consensus groups continue to argue that apolipoprotein B (apoB) should not be introduced broadly into clinical care. But, too often, the present approach to clinical care is not succeeding. An important reason for this failure, we believe, is that the conventional approach limits what the expert clinician can accomplish and is too complex, confusing, and contradictory for primary care physicians to apply effectively in their practise.
RECENT FINDINGS
There are four major reasons that apoB should be measured routinely in clinical care. First, apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C. Second, the measurement of apoB is standardized whereas the measurements of LDL-C and non-HDL-C are not. Third, with apoB and a conventional lipid panel, all the lipid phenotypes can be simply and accurately distinguished. This will improve the care of the expert. Fourth, apoB, as the single measure to evaluate the success of therapy, would simplify the process of care for primary care physicians.
SUMMARY
By introducing apoB broadly into clinical care, the process of care will be improved for both the expert and the primary care physician, and this will improve the outcomes of care.
Topics: Humans; Apolipoproteins B; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Lipoproteins; Cardiovascular Diseases
PubMed: 37934698
DOI: 10.1097/HCO.0000000000001100 -
Frontiers in Endocrinology 2023Previous findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to...
BACKGROUND
Previous findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to explore whether higher RC levels may be associated with hypertension beyond LDL-C in the general US adult population.
METHODS
This study included 10,842 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted multivariable logistic regression models were used to estimate the odds ratios (ORs) of hypertension for LDL-C and RC. We also performed analyses examining the association between hypertension and LDL-C vs. RC concordant/discordant groups.
RESULTS
A total of 4,963 (41.54%, weighted) individuals had hypertension. The weighted median levels were LDL-C: 118mg/dL, RC: 20mg/dL. At lower LDL-C clinical cut-point, the proportion of discordantly high RC dramatically increased. After multivariable adjustment, log RC was associated with higher prevalence of hypertension [OR 2.54, 95% confidence interval (CI) 2.17-2.99]. Participants with the highest tertile of RC were more likely to have hypertension (OR 2.18; 95% CI 1.89-2.52) compared with those with the lowest tertile of RC. This association remained marked after including body mass index (BMI), LDL-C, high-density lipoprotein cholesterol (HDL-C) or triglycerides. The association between LDL-C and hypertension was absent after adjusting for BMI, RC or triglycerides. Compared with low LDL-C/low RC group, the discordant low LDL-C/high RC group was associated with hypertension (OR 2.04; 95% CI 1.72-2.42), whereas the high LDL-C/low RC group was not, regardless of BMI, HDL-C or triglycerides. Similar results were observed when examining discordance among different clinical cut-points, except for the cut-point of LDL-C 70 mg/dL and RC 13 mg/dL. To better understand the association, we performed an additional analysis, which showed that among participants with apolipoprotein B < median (92mg/dL), those with discordant RC ≥ median (20mg/dL) had significantly higher odds of having hypertension (OR 1.73; 95% CI 1.38-2.17).
CONCLUSION
RC was associated with hypertension beyond LDL-C in the general US adult population. This association went beyond increased triglycerides levels, and lipoproteins other than apoB may be involved.
Topics: Adult; Humans; Cholesterol, LDL; Nutrition Surveys; Cholesterol; Cholesterol, HDL; Triglycerides; Hypertension; Apolipoproteins B; Hyperlipidemias
PubMed: 37842298
DOI: 10.3389/fendo.2023.1260764 -
Journal of the American College of... Jan 2024
Topics: Humans; Lipoprotein(a); Apolipoproteins B; Lipoproteins, LDL
PubMed: 38233013
DOI: 10.1016/j.jacc.2023.11.008 -
Journal of Diabetes Investigation Oct 2023In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends... (Review)
Review
In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.
Topics: Humans; Glycosylphosphatidylinositols; Diabetes Mellitus, Type 2; Endothelial Cells; Acute Disease; Pancreatitis; Hypertriglyceridemia; Carrier Proteins; Triglycerides; Lipoproteins, LDL; Lipoproteins, HDL; Angiopoietin-Like Protein 3; Proteins
PubMed: 37448184
DOI: 10.1111/jdi.14056 -
Diabetes, Obesity & Metabolism Nov 2023To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD).
AIM
To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD).
METHODS
All participants underwent abdominal magnetic resonance imaging on the same 3.0-Tesla scanner and IPFD was quantified. Blood samples were collected in the fasted state for analysis of lipid panel components. A series of linear regression analyses was conducted, adjusting for age, sex, ethnicity, body mass index, fasting plasma glucose, homeostatic model assessment of insulin resistance, and liver fat deposition.
RESULTS
A total of 348 participants were included. Remnant cholesterol (P = 0.010) and triglyceride levels (P = 0.008) were positively, and high-density lipoprotein cholesterol level (P = 0.001) was negatively, associated with total IPFD in the most adjusted model. Low-density lipoprotein cholesterol and total cholesterol were not significantly associated with total IPFD. Of the lipid panel components investigated, remnant cholesterol explained the greatest proportion (9.9%) of the variance in total IPFD.
CONCLUSION
Components of the lipid panel have different associations with IPFD. This may open up new opportunities for improving outcomes in people at high risk for cardiovascular diseases (who have normal low-density lipoprotein cholesterol) by reducing IPFD.
Topics: Humans; Cholesterol, LDL; Pancreas; Cholesterol; Body Mass Index; Insulin Resistance; Triglycerides; Cholesterol, HDL
PubMed: 37529874
DOI: 10.1111/dom.15233 -
Journal of Innate Immunity 2024Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role... (Review)
Review
BACKGROUND
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and is involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host's response.
SUMMARY
This review compiles the current knowledge of potential implications of LOX-1 in inflammatory processes and in host-pathogen interactions with a particular emphasis on its regulatory role in immune responses. Also discussed are genomic and structural variations found in LOX-1 homologs across different species as well as potential involvements of LOX-1 in inflammatory processes from the angle of different cell types and organ-specific interactions.
KEY MESSAGES
The results presented reveal both similar and different structures in human and murine LOX-1 and provide clues as to the possible origins of different modes of interaction. These descriptions raise concerns about the suitability, particularly of mouse models, that are often used in the analysis of its functionality in humans. Further research should also aim to better understand the mostly unknown binding and interaction mechanisms between LOX-1 and different pathogens. This pursuit will not only enhance our understanding of LOX-1 involvement in inflammatory processes but also identify potential targets for immunomodulatory approaches.
Topics: Animals; Humans; Mice; Atherosclerosis; Host-Pathogen Interactions; Inflammation; Lipoproteins, LDL; Scavenger Receptors, Class E
PubMed: 38232720
DOI: 10.1159/000535793 -
Immunology Letters Nov 2023Efferocytosis dysfunction contributes to the progression and rupture of atherosclerotic plaques. Efferocytosis is crucially modulated by intracytoplasmic Ca, and...
OBJECTIVE
Efferocytosis dysfunction contributes to the progression and rupture of atherosclerotic plaques. Efferocytosis is crucially modulated by intracytoplasmic Ca, and mitochondrial calcium uniporter (MCU) complex proteins serve as key channels for regulating Ca concentration. Therefore, it was speculated that MCU may affect the development of atherosclerosis (AS) by regulating efferocytosis. In the present study, we aimed to investigate whether MCU could affect foam cell formation by regulating efferocytosis.
METHODS
We stimulated primary macrophages (Møs) using oxidized low-density lipoprotein (ox-LDL) to mimic the atherosclerotic microenvironment and treated them with Ru360, an MCU-specific inhibitor, and UNC1062, an inhibitor of efferocytosis. Additionally, we conducted double staining to determine the Mø efferocytosis rate. We measured the expression of MCU complexes and efferocytosis-associated proteins using western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, we separately detected the Ca level in the cytoplasm and mitochondria (MT) using Fluo-4 AM and Rhod-2 methods. We separately determined the reactive oxygen species (ROS) level in cytoplasm and MT using dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probing method and Mito-SOXTM superoxide indicator staining. Additionally, we conducted the enzyme-linked immunosorbent assay (ELISA) to detect the production of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). Oil Red O staining was performed to measure cytoplasmic lipid levels.
RESULTS
Ru360 attenuated ox-LDL-induced efferocytosis dysfunction, and attenuated the upregulation of MCU and MCUR1 induced by ox-LDL, and meanwhile attenuated the downregulation of MCUb induced by ox-LDL. Ru360 attenuated the decrease of intracytoplasmic Ca concentration induced by ox- LDL, Ru360 also attenuated the ROS production induced by ox- LDL, attenuated the release of IL-6, IL-18, IL-1β, and TNF-α induced by ox- LDL, and attenuated the increase of intracytoplasmic lipid content induced by ox-LDL. UNC1062 attenuated the effects of Ru360 in reducing inflammatory cytokines and intracytoplasmic lipid content.
CONCLUSIONS
In this study, we found that MCU inhibition modulated intracytoplasmic Ca concentration, improved impaired Mø efferocytosis, and reduced ROS generation. Macrophage efferocytosis removed apoptotic cells and prevented the release of inflammatory factor and foam cell formation, and this can be a potential new therapeutic target for alleviating atherosclerosis.
Topics: Animals; Mice; Reactive Oxygen Species; Interleukin-18; Tumor Necrosis Factor-alpha; Interleukin-6; Disease Models, Animal; Macrophages; Lipoproteins, LDL; Atherosclerosis
PubMed: 37689315
DOI: 10.1016/j.imlet.2023.09.003 -
Cell Metabolism Jul 2023Although the role of inflammation in atherosclerosis is established, whether this relationship remains important after lowering low-density lipoprotein cholesterol...
Although the role of inflammation in atherosclerosis is established, whether this relationship remains important after lowering low-density lipoprotein cholesterol (LDL-C) is still unclear. Recently in The Lancet, Ridker et al. demonstrated that residual inflammatory risk was a stronger predictor of fatal and non-fatal events compared to residual cholesterol risk, supporting the concept of inflammation testing to guide vascular risk reduction.
Topics: Humans; Cholesterol; Cholesterol, LDL; Atherosclerosis; Inflammation
PubMed: 37437543
DOI: 10.1016/j.cmet.2023.06.011 -
Annales de Biologie Clinique Nov 2023Dyslipidemia plays an essential role in the occurrence and development of cardiovascular diseases, and the regulation of cholesterol and triglyceride metabolism has been...
Dyslipidemia plays an essential role in the occurrence and development of cardiovascular diseases, and the regulation of cholesterol and triglyceride metabolism has been applied in the diagnosis, treatment and prognosis of clinical cardiovascular diseases. Following advances in methodology in recent years, low-density lipoprotein triglycerides (LDL-TG) has been identified as a potential risk factor for the development of cardiovascular disease and has some clinical significance in its diagnosis and treatment. Meanwhile, LDL-TG metabolism regulation may also be involved in the development of type 2 diabetes, chronic kidney disease, hypothyroidism and other diseases, which may improve our understanding of the prevention, control and risk assessment of clinically relevant diseases.
Topics: Humans; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Cholesterol, LDL; Triglycerides; Risk Factors; Metabolic Diseases; Cholesterol, HDL
PubMed: 38018855
DOI: 10.1684/abc.2023.1840