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International Journal of Environmental... Jul 2022Numerous studies have demonstrated that abnormal levels of cholesterol are associated with a high attributable risk for the occurrence of cardiovascular disease (CVD).... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Numerous studies have demonstrated that abnormal levels of cholesterol are associated with a high attributable risk for the occurrence of cardiovascular disease (CVD). However, there has been no comprehensive study to investigate the relationship between serum cholesterol levels and cardiovascular mortality. Therefore, we conducted a systematic review and dose-response meta-analysis.
METHODS
A systematic literature search of key databases, including EMBASE and MEDLINE, was conducted and included all the published epidemiological studies that contained estimates of the hazard ratios (HR) of serum cholesterol of CVD mortality. Data extraction, eligibility, and assessment of the risk of bias were assessed by two reviewers independently. All published risk estimates were hazard ratios and analyzed by quantitative meta-analysis using a random-effects model and dose-response relationships of serum cholesterol with CVD mortality.
RESULTS
A total of 14 independent reports, including 1,055,309 subjects and 9457 events, were analyzed. The pooled HR (95% CI) was 1.27 (95% CI, 1.19-1.36) for total cholesterol, 1.21 (95% CI, 1.09-1.35) for low-density lipoprotein cholesterol (LDL-C), and 0.60 (95% CI, 0.50-0.72) for high-density lipoprotein cholesterol (HDL-C). We observed a linear association between serum cholesterol (TC, HDL-C) levels and CVD mortality in this meta-analysis.
CONCLUSIONS
Serum total cholesterol and LDL-C level is associated with increased CVD mortality, but HDL-C level is inversely associated with CVD mortality.
Topics: Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Humans; Prospective Studies; Risk Factors; Triglycerides
PubMed: 35886124
DOI: 10.3390/ijerph19148272 -
British Journal of Pharmacology Aug 2021
Topics: Cholesterol; Oxysterols
PubMed: 34278569
DOI: 10.1111/bph.15577 -
Redox Biology Feb 2022More and more attention is nowadays given to the possible translational application of a great number of biochemical and biological findings with the involved molecules.... (Review)
Review
More and more attention is nowadays given to the possible translational application of a great number of biochemical and biological findings with the involved molecules. This is also the case of cholesterol oxidation products, redox molecules over the last years deeply investigated for their implication in human pathophysiology. Oxysterols of non-enzymatic origin, the excessive increase of which in biological fluids and tissues is of toxicological relevance for their marked pro-oxidant and pro-inflammatory properties, are increasingly applied in clinical biochemistry as molecular markers in the diagnosis and monitoring of several human and veterinary diseases. Conversely, oxysterols of enzymatic origin, the production of which is commonly under physiological regulation, could be considered and tested as promising pharmaceutical agents because of their antiviral, pro-osteogenic and antiadipogenic properties of some of them. Very recently, the quantification of oxysterols of non-enzymatic origin has been adopted in a systematic way to evaluate, monitor and improve the quality of cholesterol-based food ingredients, that are prone to auto-oxidation, as well as their industrial processing and the packaging and the shelf life of the finished food products. The growing translational value of oxysterols is here reviewed in its present and upcoming applications in various industrial fields.
Topics: Biomarkers; Cholesterol; Humans; Hydroxycholesterols; Oxidation-Reduction; Oxysterols
PubMed: 34968886
DOI: 10.1016/j.redox.2021.102220 -
British Journal of Pharmacology Aug 2021Oxysterols are oxygenated forms of cholesterol generated via autooxidation by free radicals and ROS, or formed enzymically by a variety of enzymes such as those involved... (Review)
Review
Oxysterols are oxygenated forms of cholesterol generated via autooxidation by free radicals and ROS, or formed enzymically by a variety of enzymes such as those involved in the synthesis of bile acids. Although found at very low concentrations in vivo, these metabolites play key roles in health and disease, particularly in development and regulating immune cell responses, by binding to effector proteins such as LXRα, RORγ and Insig and directly or indirectly regulating transcriptional programmes that affect cell metabolism and function. In this review, we summarise the routes by which oxysterols can be generated and subsequently modified to other oxysterol metabolites and highlight their diverse and profound biological functions and opportunities to alter their levels using pharmacological approaches. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.
Topics: Cholesterol; Immunity; Oxysterols
PubMed: 32335907
DOI: 10.1111/bph.15073 -
Deutsches Arzteblatt International Sep 2023The treatment of dyslipidemias plays a major role in the primary and secondary prevention of cardiovascular disease. Proper evaluation of the patient's lipid status is... (Review)
Review
BACKGROUND
The treatment of dyslipidemias plays a major role in the primary and secondary prevention of cardiovascular disease. Proper evaluation of the patient's lipid status is very important for risk assessment and as a guide to treatment.
METHODS
This review is based on publications retrieved by a selective search of the literature, including current guidelines.
RESULTS
Measurement of the plasma concentration of cholesterol, triglycerides, HDL- and LDL-cholesterol, calculation of the non-HDL cholesterol concentration, and-on a single occasion-determination of the lipoprotein (a) concentration enable the clinician to quantify the lipid-associated health risk and monitor the effects of treatment. These blood tests can be performed in a non-fasting state except in special situations (particularly, hypertriglyceridemia). The HDL quotient is an obsolete measure. The main goal of treatment is to achieve an LDL-cholesterol level adequate to the patient's cardiovascular risk through lifestyle modification and, if necessary, medication. A high lipoprotein (a) concentration cannot be lowered with orally administered drugs; above all, patients should lower their LDL-cholesterol levels while minimizing all other risk factors.
CONCLUSION
Measurement of the concentration of cholesterol, triglycerides, and HDL- and LDL-cholesterol and calculation of the non-HDL-C suffice as a guide to lipid-lowering treatment. The primary therapeutic goal is to lower LDL cholesterol.
Topics: Humans; Lipoprotein(a); Cholesterol, HDL; Cholesterol; Triglycerides; Cholesterol, LDL; Risk Factors
PubMed: 37403458
DOI: 10.3238/arztebl.m2023.0150 -
South African Family Practice :... Oct 2023Vitamin D is a fat-soluble molecule referring to the different isoforms, ergocalciferol (D2) and cholecalciferol (D3). Its physiological functions include increasing... (Review)
Review
Vitamin D is a fat-soluble molecule referring to the different isoforms, ergocalciferol (D2) and cholecalciferol (D3). Its physiological functions include increasing calcium serum concentrations. 25-hydroxyvitamin D3 (25(OH)D) (Calcifediol), a non-active, circulating instant precursor is seen as a pre-hormone. Studies have shown that a deficiency in calcifediol is related to chronic conditions such as cardiovascular, musculoskeletal, immune system, neurological, and anti-neoplastic functions. Vitamin D supplementation has shown its benefit as prophylaxis and treatment during the coronavirus disease 2019 (COVID-19) pandemic and an increase in the prescribing of vitamin D supplementation has been observed. The intention of this review article is to provide guidance on the recommended dosage regimen as a prophylactic measure during COVID-19 and its use as a supplement in general. From this review article, it is clear that vitamin D has an important role to play not only in COVID-19 but also in various other health aspects of the human body.Contribution: This review article highlighted the role of vitamin D in managing vitamin D deficiency and its role as a supplement in the management of respiratory tract infections, especially COVID-19. This overview can assist physicians in optimising healthcare by optimised dosing recommendations and indications.
Topics: Humans; Calcifediol; Ergocalciferols; Pandemics; Vitamin D; Vitamins; Dietary Supplements; Cholestanes; COVID-19
PubMed: 37916701
DOI: 10.4102/safp.v65i1.5752 -
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 -
Journal of Lipid Research Dec 2023Oncosterone (6-oxo-cholestane-3β,5α-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha-positive breast cancer (ER(+) BC) and...
Oncosterone (6-oxo-cholestane-3β,5α-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha-positive breast cancer (ER(+) BC) and triple-negative breast cancers (TN BC). OCDO is an oxysterol formed in three steps from cholesterol: 1) oxygen addition at the double bond to give α- or β- isomers of 5,6-epoxycholestanols (5,6-EC), 2) hydrolyses of the epoxide ring of 5,6-ECs to give cholestane-3β,5α,6β-triol (CT), and 3) oxidation of the C6 hydroxyl of CT to give OCDO. On the other hand, cholesterol can be hydroxylated by CYP27A1 at the ultimate methyl carbon of its side chain to give 27-hydroxycholesterol ((25R)-Cholest-5-ene-3beta,26-diol, 27HC), which is a tumor promoter for ER(+) BC. It is currently unknown whether OCDO and its precursors can be hydroxylated at position C27 by CYP27A1, as is the impact of such modification on the proliferation of ER(+) and TN BC cells. We investigated, herein, whether 27H-5,6-ECs ((25R)-5,6-epoxycholestan-3β,26-diol), 27H-CT ((25R)-cholestane-3β,5α,6β,26-tetrol) and 27H-OCDO ((25R)-cholestane-6-oxo-3β,5α,26-triol) exist as metabolites and can be produced by cells expressing CYP27A1. We report, for the first time, that these compounds exist as metabolites in humans. We give pharmacological and genetic evidence that CYP27A1 is responsible for their production. Importantly, we found that 27-hydroxy-OCDO (27H-OCDO) inhibits BC cell proliferation and blocks OCDO and 27-HC-induced proliferation in BC cells, showing that this metabolic conversion commutes the proliferative properties of OCDO into antiproliferative ones. These data suggest an unprecedented role of CYP27A1 in the control of breast carcinogenesis by inhibiting the tumor promoter activities of oncosterone and 27-HC.
Topics: Humans; Female; Hydroxylation; Cholesterol; Breast Neoplasms; Oxysterols; Cytochrome P-450 Enzyme System; Carcinogens; Cholestanetriol 26-Monooxygenase
PubMed: 37981011
DOI: 10.1016/j.jlr.2023.100479 -
Molecules (Basel, Switzerland) Apr 2013Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes,... (Review)
Review
Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes, required for proper membrane permeability and fluidity. The last part of the pathway involves steroidal triterpenes with cholestane ring structures. It starts by conversion of acyclic squalene into lanosterol, the first sterol intermediate of the pathway, followed by production of 20 structurally very similar steroidal triterpene molecules in over 11 complex enzyme reactions. Due to the structural similarities of sterol intermediates and the broad substrate specificity of the enzymes involved (especially sterol-Δ24-reductase; DHCR24) the exact sequence of the reactions between lanosterol and cholesterol remains undefined. This article reviews all hitherto known structures of post-squalene steroidal triterpenes of cholesterol synthesis, their biological roles and the enzymes responsible for their synthesis. Furthermore, it summarises kinetic parameters of enzymes (Vmax and Km) and sterol intermediate concentrations from various tissues. Due to the complexity of the post-squalene cholesterol synthesis pathway, future studies will require a comprehensive meta-analysis of the pathway to elucidate the exact reaction sequence in different tissues, physiological or disease conditions. A major reason for the standstill of detailed late cholesterol synthesis research was the lack of several steroidal triterpene standards. We aid to this efforts by summarizing commercial and laboratory standards, referring also to chemical syntheses of meiosis-activating sterols.
Topics: Animals; Cholesterol; Lanosterol; Metabolomics; Models, Animal; Squalene; Steroids; Sterols; Triterpenes
PubMed: 23558541
DOI: 10.3390/molecules18044002 -
Proceedings of the Royal Society of... Jun 1951
Topics: Cholestanes; Humans; Rickets; Vitamin D; Vitamins
PubMed: 14864529
DOI: No ID Found