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Biomedicines
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Lipid and Lipoprotein Metabolism in Human Health and Diseases
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Lipid and Lipoprotein Metabolism in Human Health and Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 10115

Special Issue Editors

Dr. Ilenia Calcaterra

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Guest Editor
Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
Interests: familial hypercholesterolemia; cardiovascular disease lipoprotein; lipidomic
Special Issues, Collections and Topics in MDPI journals
Dr. Alessandro Di Minno

E-Mail Website
Guest Editor
Department of Pharmacy, Università degli Studi di Napoli Federico II, Naples, Italy
Interests: oxidative stress; cardiovascular disease; reactive oxygen species; pharmacological treatment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipids are essential components of cellular membranes and lipoproteins. Lipids play many essential roles in cellular functions, including cellular barriers, membrane matrices, signaling pathways and energy storage.

Lipid and lipoprotein metabolism represent a complex set of chemical reactions involving liver, bowel, and endothelial compartments. Specific proteins and enzymes are involved in this process and, when deficient, they cause human diseases (e.g., familial hypercholesterolemia (FH) or familial chylomicronemia syndrome (FCS)).

Since the 1950s, lipids have been extracted from cells or tissues and total lipid extracts have been analyzed by chromatography and mass spectrometry. Over the years, the detailed study of lipid and lipoprotein metabolism has led to greater knowledge of the pathophysiological mechanisms of dyslipidemias. Furthermore, the identification of new therapeutic targets has allowed for the treatment of pathologies that were orphaned until a few years ago (e.g., PCSK9, ANGPTL-3, ApoCIII and MTP inhibition).

New perspectives are emerging from novel laboratory approaches, in particular omics studies. The results of these studies are promising in identifying novel biomarkers that will help in the diagnosis, prognosis and treatment of human diseases (e.g., cancer and atherosclerotic vascular diseases). Moreover, a promising application is the characterization of endpoints in clinical trials, which remains a major issue in drug development.

The aim of the Special Issue is to give an update on new evidence in studies on lipid metabolism and multi-omics evaluations and to clarify the molecular features of human disease, particularly in hereditary lipid disorders. The present Special Issue is addressed towards basic and clinical research.  Reviews and original research articles are welcome. The topics included in the Special Issue are the following:

  • The role of lipids in various physiological processes and pathophysiological mechanisms of human disease;
  • The evaluation of lipidome modifications following pharmacological intervention;
  • Novel laboratory approaches (multi-omics) to human disease, in particular lipid disorders and atherosclerosis.

Dr. Ilenia Calcaterra
Dr. Alessandro Di Minno
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lipoprotein
  • lipid metabolism
  • lipidome
  • lipidomics
  • mass spectrometry
  • hereditary lipid disorders
  • familial hypercholesterolemia
  • omic
  • metabolomic
  • genomic

Related Special Issue

Published Papers (5 papers)

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Research

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11 pages, 1053 KiB  
Article
Lipoprotein(a) As a Potential Predictive Factor for Earlier Aortic Valve Replacement in Patients with Bicuspid Aortic Valve
by Aleksandra Krzesińska, Maria Nowak, Agnieszka Mickiewicz, Gabriela Chyła-Danił, Agnieszka Ćwiklińska, Olga M. Koper-Lenkiewicz, Joanna Kamińska, Joanna Matowicka-Karna, Marcin Gruchała, Maciej Jankowski, Marcin Fijałkowski and Agnieszka Kuchta
Biomedicines 2023, 11(7), 1823; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11071823 - 25 Jun 2023
Viewed by 1009
Abstract
Bicuspid aortic valve (BAV) affects 0.5–2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk [...] Read more.
Bicuspid aortic valve (BAV) affects 0.5–2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk of AVS developing in BAV patients, with particular emphasis on lipoprotein(a) (Lp(a)), which is a well-recognized risk factor for stenosis in the general population. We also analyzed the impact of autotaxin (ATX) and interleukin-6 (IL-6) as parameters potentially related to the pathomechanism of Lp(a) action. We found that high Lp(a) levels (>50 mg/dL) occurred significantly more frequently in patients with AVS than in patients without AVS, both in the group below and above 45 years of age (p = 0.036 and p = 0.033, respectively). Elevated Lp(a) levels were also strictly associated with the need for aortic valve replacement (AVR) at a younger age (p = 0.016). However, the Lp(a) concentration did not differ significantly between patients with and without AVS. Similarly, we observed no differences in ATX between the analyzed patient groups, and both ATX activity and concentration correlated significantly with Lp(a) level (R = 0.465, p < 0.001 and R = 0.599, p < 0.001, respectively). We revealed a significantly higher concentration of IL-6 in young patients with AVS. However, this observation was not confirmed in the group of patients over 45 years of age. We also did not observe a significant correlation between IL-6 and Lp(a) or between CRP and Lp(a) in any of the analyzed groups of BAV patients. Our results demonstrate that a high level of Lp(a), greater than 50 mg/dL, may be a significant predictive factor for earlier AVR. Lp(a)-related parameters, such as ATX and IL-6, may be valuable in providing information about the additional cardiovascular risks associated with developing AVS. Full article
(This article belongs to the Special Issue Lipid and Lipoprotein Metabolism in Human Health and Diseases)
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12 pages, 1874 KiB  
Article
Comparison of Two Nuclear Magnetic Resonance Spectroscopy Methods for the Measurement of Lipoprotein Particle Concentrations
by Martin Rief, Reinhard Raggam, Peter Rief, Philipp Metnitz, Tatjana Stojakovic, Markus Reinthaler, Marianne Brodmann, Winfried März, Hubert Scharnagl and Günther Silbernagel
Biomedicines 2022, 10(7), 1766; https://doi.org/10.3390/biomedicines10071766 - 21 Jul 2022
Cited by 3 | Viewed by 1424
Abstract
Background: Measuring lipoprotein particle concentrations may help to improve cardiovascular risk stratification. Both the lipofit (Numares) and lipoprofile (LabCorp) NMR methods are widely used for the quantification of lipoprotein particle concentrations. Objective: The aim of the present work was to perform a method [...] Read more.
Background: Measuring lipoprotein particle concentrations may help to improve cardiovascular risk stratification. Both the lipofit (Numares) and lipoprofile (LabCorp) NMR methods are widely used for the quantification of lipoprotein particle concentrations. Objective: The aim of the present work was to perform a method comparison between the lipofit and lipoprofile NMR methods. In addition, there was the objective to compare lipofit and lipoprofile measurements of standard lipids with clinical chemistry-based results. Methods: Total, LDL, and HDL cholesterol and triglycerides were measured with ß-quantification in serum samples from 150 individuals. NMR measurements of standard lipids and lipoprotein particle concentrations were performed by Numares and LabCorp. Results: For both NMR methods, differences of mean concentrations compared to ß-quantification-derived measurements were ≤5.5% for all standard lipids. There was a strong correlation between ß-quantification- and NMR-derived measurements of total and LDL cholesterol and triglycerides (all r > 0.93). For both, the lipofit (r = 0.81) and lipoprofile (r = 0.84) methods, correlation coefficients were lower for HDL cholesterol. There was a reasonable correlation between LDL and HDL lipoprotein particle concentrations measured with both NMR methods (both r > 0.9). However, mean concentrations of major and subclass lipoprotein particle concentrations were not as strong. Conclusions: The present analysis suggests that reliable measurement of standard lipids is possible with these two NMR methods. Harmonization efforts would be needed for better comparability of particle concentration data. Full article
(This article belongs to the Special Issue Lipid and Lipoprotein Metabolism in Human Health and Diseases)
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12 pages, 687 KiB  
Article
Association between Cholesterol Level and the Risk of Hematologic Malignancy According to Menopausal Status: A Korean Nationwide Cohort Study
by Wonyoung Jung, Keun Hye Jeon, Jihun Kang, Taewoong Choi, Kyungdo Han, Sang-Man Jin, Su-Min Jeong and Dong Wook Shin
Biomedicines 2022, 10(7), 1617; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071617 - 06 Jul 2022
Cited by 2 | Viewed by 1320
Abstract
Recent studies have revealed the possible association between serum cholesterol levels and hematologic malignancy (HM). However, limited information is available about how reproductive factors interact with this association. Therefore, we investigated the roles of serum cholesterol in the risk of HM according to [...] Read more.
Recent studies have revealed the possible association between serum cholesterol levels and hematologic malignancy (HM). However, limited information is available about how reproductive factors interact with this association. Therefore, we investigated the roles of serum cholesterol in the risk of HM according to the menopausal status. We finally identified 1,189,806 premenopausal and 1,621,604 postmenopausal women who underwent a national health screening program in 2009 using data from the Korean National Health Insurance Service database. Overall, 5449 (0.19%) developed HM. Among postmenopausal women, the inverse associations were observed between total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) levels, and the risk of overall HM. In premenopausal women, the highest quartile of HDL-C was associated with a reduced risk of HM compared with the lowest quartile of HDL-C consistent with results in postmenopausal women (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] [0.68–0.95]), whereas the highest quartile of triglyceride (TG) showed an increased risk of HM compared to the lowest quartile of TG, (aHR 1.22, 95% CI [1.02,1.44]) only in premenopausal women. Our finding suggests that lipid profiles are differently associated with HM risk by menopausal status. Full article
(This article belongs to the Special Issue Lipid and Lipoprotein Metabolism in Human Health and Diseases)
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13 pages, 658 KiB  
Article
The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs
by Günther Silbernagel, Hubert Scharnagl, Christoph H. Saely, Markus Reinthaler, Martin Rief, Marcus E. Kleber, Barbara Larcher, John Chapman, Juergen R. Schaefer, Heinz Drexel and Winfried März
Biomedicines 2022, 10(6), 1302; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10061302 - 02 Jun 2022
Cited by 5 | Viewed by 3046
Abstract
Background and Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the [...] Read more.
Background and Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, dense LDLs. Methods: LDLC and LDLapoB were measured (beta-quantification) and calculated (according to Friedewald and Baca, respectively) for 3291 participants of the LURIC Study, with a median (inter-quartile range) follow-up for cardiovascular mortality of 9.9 (8.7–10.7) years. An independent replication cohort included 1660 participants. Associations of the LDLapoB/LDLC ratio with LDL subclass particle concentrations (ultracentrifugation) were tested for 282 participants. Results: In the LURIC Study, the mean (standard deviation) LDLC and LDLapoB concentrations were 117 (34) and 85 (22) mg/dL, respectively; 621 cardiovascular deaths occurred. Elevated LDLapoB/LDLC (calculated and measured) ratios were significantly and independently associated with increased cardiovascular mortality in the entire cohort (fourth vs. first quartile: hazard ratio (95% confidence interval) = 2.07 (1.53–2.79)) and in statin-naïve patients. The association between calculated LDLapoB/LDLC ratio and cardiovascular mortality was replicated in an independent cohort. High LDLapoB/LDLC ratios were associated with higher LDL5 and LDL6 concentrations (both p < 0.001), but not with concentrations of larger LDLs. Conclusions: Elevated measured and calculated LDLapoB/LDLC ratios are associated with increased cardiovascular mortality. Use of LDLapoB/LDLC ratios allows estimation of the atherogenic risk conferred by small, dense LDLs. Full article
(This article belongs to the Special Issue Lipid and Lipoprotein Metabolism in Human Health and Diseases)
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Review

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19 pages, 1788 KiB  
Review
Apolipoprotein A-II, a Player in Multiple Processes and Diseases
by Gabriela Florea, Irina Florina Tudorache, Elena Valeria Fuior, Radu Ionita, Madalina Dumitrescu, Ioana Madalina Fenyo, Violeta Georgeta Bivol and Anca Violeta Gafencu
Biomedicines 2022, 10(7), 1578; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071578 - 02 Jul 2022
Cited by 13 | Viewed by 2444
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Lipid and Lipoprotein Metabolism in Human Health and Diseases)
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