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Cholesterol and Lipoprotein Metabolism 2019
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Cholesterol and Lipoprotein Metabolism 2019

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 21808

Special Issue Editor

Prof. Dr. Bart De Geest

E-Mail Website
Guest Editor
Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Campus Gasthuisberg, Herestraat 49 bus 911, 3000 Leuven, Belgium
Interests: lipoproteins; atherosclerosis; coronary heart disease; familial hypercholesterolemia; low-density lipoprotein (LDL) receptor; heart failure; gene therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cholesterol is an essential structural component of all animal cell membranes and is critical as a determinant of both membrane structural integrity and fluidity. Inborn errors of cholesterol synthesis, like the Smith–Lemli–Opitz syndrome, cause a broad spectrum of effects. On the other hand, the accumulation of cholesterol in the vascular wall is a cardinal feature of atherosclerosis and had already been demonstrated in 1910 by the German chemist and Nobel Prize winner A. Windaus in studies on human atherosclerotic lesions.

Hypercholesterolemia is a risk factor for atherosclerotic vascular disease but its biological and clinical impact is much broader. In the past years, major advances in pharmacological treatment of hypercholesterolemia were realised. The FOURIER trial, evaluating the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab, met both its primary composite endpoint (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or coronary revascularization) and the more rigorous key secondary composite endpoint (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). The ODYSSEY OUTCOMES evaluating the PCSK9 inhibitor alirocumab also met its primary endpoint. The cost price of PCSK9 inhibitors remains a major obstacle for broad clinical application.

In general, a strong linear relationship has been demonstrated between absolute low-density lipoprotein (LDL)-cholesterol reduction (mmol/L) and reduction of the rate of major cardiovascular events (%). In contrast, the high-density lipoprotein (HDL) hypothesis, which states that raising HDL may lead to a decrease in coronary heart disease risk, remains unproven. At present, the scientific field of cholesterol and lipoprotein metabolism remains an inexhaustible source of challenging questions and discovery and extends far beyond the field of atherosclerosis and ischemic cardiovascular diseases. This Special Issue will cover recent advances in basic science and clinical translation investigations in these fields.

Prof. Dr. Bart De Geest
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Cholesterol
  • Lipoprotein metabolism
  • Low-density lipoproteins
  • High-density lipoproteins
  • Remnant lipoproteins
  • Apolipoprotein B
  • Apolipoprotein A-I
  • Proprotein convertase subtilisin/kexin type 9
  • Atherosclerotic vascular disease
  • Cholesterol ester transfer protein
  • Ischemic cardiovascular disease
  • Heart failure

Published Papers (4 papers)

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Research

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15 pages, 763 KiB  
Article
Atorvastatin and Fenofibrate Increase the Content of Unsaturated Acyl Chains in HDL and Modify In Vivo Kinetics of HDL-Cholesteryl Esters in New Zealand White Rabbits
by Cristóbal Flores-Castillo, María Luna-Luna, Elizabeth Carreón-Torres, Victoria López-Olmos, Sara Frías, Marco Antonio Juárez-Oropeza, Martha Franco, José Manuel Fragoso, Gilberto Vargas-Alarcón and Óscar Pérez-Méndez
Int. J. Mol. Sci. 2019, 20(10), 2521; https://doi.org/10.3390/ijms20102521 - 22 May 2019
Cited by 8 | Viewed by 3040
Abstract
Previous studies demonstrated modifications of high-density lipoproteins (HDL) structure and apolipoprotein (apo) A-I catabolism induced by the atorvastatin and fenofibrate combination. However, it remains unknown whether such structural and metabolic changes of HDL were related to an improvement of the HDL-cholesteryl esters (HDL-CE) [...] Read more.
Previous studies demonstrated modifications of high-density lipoproteins (HDL) structure and apolipoprotein (apo) A-I catabolism induced by the atorvastatin and fenofibrate combination. However, it remains unknown whether such structural and metabolic changes of HDL were related to an improvement of the HDL-cholesteryl esters (HDL-CE) metabolism. Therefore, we determined the structure of HDL and performed kinetic studies of HDL-CE radiolabeled with tritium in rabbits treated with atorvastatin, fenofibrate, and a combination of both drugs. The atorvastatin and fenofibrate combination increased the HDL size and the cholesterol and phospholipid plasma concentrations of the largest HDL subclasses. Moreover, the relative amount of unsaturated fatty acids contained in HDL increased, in detriment of saturated fatty acids as determined by gas chromatography–mass spectrometry. The transfers of cholesteryl esters (CE) from HDL to very low-density lipoproteins/low-density lipoproteins (VLDL/LDL) and vice versa were enhanced with atorvastatin, alone or in combination. Moreover, the direct elimination of CE from plasma via VLDL/LDL decreased with fenofibrate, whereas the direct elimination of CE via HDL augmented with the combination treatment. Taken together, the rise of unsaturated fatty acid content and the size increase of HDL, suggest that atorvastatin and fenofibrate induce more fluid HDL particles, which in turn favor an enhanced CE exchange between HDL and VLDL/LDL. Our results contribute to a better understanding of the relationship between the structure and function of HDL during the use of anti-dyslipidemic drugs. Full article
(This article belongs to the Special Issue Cholesterol and Lipoprotein Metabolism 2019)
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20 pages, 9242 KiB  
Article
Cholesterol-Lowering Gene Therapy Prevents Heart Failure with Preserved Ejection Fraction in Obese Type 2 Diabetic Mice
by Joseph Pierre Aboumsallem, Ilayaraja Muthuramu, Mudit Mishra and Bart De Geest
Int. J. Mol. Sci. 2019, 20(9), 2222; https://doi.org/10.3390/ijms20092222 - 06 May 2019
Cited by 10 | Viewed by 3457
Abstract
Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)−/− mice. Secondly, [...] Read more.
Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)−/− mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure–volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF. Full article
(This article belongs to the Special Issue Cholesterol and Lipoprotein Metabolism 2019)
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Review

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25 pages, 8241 KiB  
Review
Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond
by Elena V. Fuior and Anca V. Gafencu
Int. J. Mol. Sci. 2019, 20(23), 5939; https://doi.org/10.3390/ijms20235939 - 26 Nov 2019
Cited by 94 | Viewed by 7596
Abstract
Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, APOC1 gene is in linkage disequilibrium with APOE gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and [...] Read more.
Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, APOC1 gene is in linkage disequilibrium with APOE gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and exchanges between lipoprotein classes. These interactions occur via amphipathic helix motifs, as demonstrated by biophysical studies on the wild-type polypeptide and representative mutants. Apolipoprotein C1 acts on lipoprotein receptors by inhibiting binding mediated by apolipoprotein E, and modulating the activities of several enzymes. Thus, apoC1 downregulates lipoprotein lipase, hepatic lipase, phospholipase A2, cholesterylester transfer protein, and activates lecithin-cholesterol acyl transferase. By controlling the plasma levels of lipids, apoC1 relates directly to cardiovascular physiology, but its activity extends beyond, to inflammation and immunity, sepsis, diabetes, cancer, viral infectivity, and—not last—to cognition. Such correlations were established based on studies using transgenic mice, associated in the recent years with GWAS, transcriptomic and proteomic analyses. The presence of a duplicate gene, pseudogene APOC1P, stimulated evolutionary studies and more recently, the regulatory properties of the corresponding non-coding RNA are steadily emerging. Nonetheless, this prototypical apolipoprotein is still underexplored and deserves further research for understanding its physiology and exploiting its therapeutic potential. Full article
(This article belongs to the Special Issue Cholesterol and Lipoprotein Metabolism 2019)
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17 pages, 1263 KiB  
Review
Atherosclerosis and Coenzyme Q10
by Juan M. Suárez-Rivero, Carmen J. Pastor-Maldonado, Mario de la Mata, Marina Villanueva-Paz, Suleva Povea-Cabello, Mónica Álvarez-Córdoba, Irene Villalón-García, Alejandra Suárez-Carrillo, Marta Talaverón-Rey, Manuel Munuera and José A. Sánchez-Alcázar
Int. J. Mol. Sci. 2019, 20(20), 5195; https://doi.org/10.3390/ijms20205195 - 20 Oct 2019
Cited by 26 | Viewed by 7233
Abstract
Atherosclerosis is the most common cause of cardiac deaths worldwide. Classically, atherosclerosis has been explained as a simple arterial lipid deposition with concomitant loss of vascular elasticity. Eventually, this condition can lead to consequent blood flow reduction through the affected vessel. However, numerous [...] Read more.
Atherosclerosis is the most common cause of cardiac deaths worldwide. Classically, atherosclerosis has been explained as a simple arterial lipid deposition with concomitant loss of vascular elasticity. Eventually, this condition can lead to consequent blood flow reduction through the affected vessel. However, numerous studies have demonstrated that more factors than lipid accumulation are involved in arterial damage at the cellular level, such as inflammation, autophagy impairment, mitochondrial dysfunction, and/or free-radical overproduction. In order to consider the correction of all of these pathological changes, new approaches in atherosclerosis treatment are necessary. Ubiquinone or coenzyme Q10 is a multifunctional molecule that could theoretically revert most of the cellular alterations found in atherosclerosis, such as cholesterol biosynthesis dysregulation, impaired autophagy flux and mitochondrial dysfunction thanks to its redox and signaling properties. In this review, we will show the latest advances in the knowledge of the relationships between coenzyme Q10 and atherosclerosis. In addition, as atherosclerosis phenotype is closely related to aging, it is reasonable to believe that coenzyme Q10 supplementation could be beneficial for both conditions. Full article
(This article belongs to the Special Issue Cholesterol and Lipoprotein Metabolism 2019)
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