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Expert Opinion on Pharmacotherapy Feb 2019Familial Hypercholesterolemia (FH) is an inherited disorder characterized by a defect in the binding and internalization of low-density lipoprotein (LDL) particles,... (Review)
Review
Familial Hypercholesterolemia (FH) is an inherited disorder characterized by a defect in the binding and internalization of low-density lipoprotein (LDL) particles, resulting in markedly elevated LDL levels and premature atherosclerosis. It is one of the most common inherited disorders of lipid metabolism. Many FH patients, especially those with homozygous FH do not reach LDL goals with traditional LDL therapies and may require additional, less often used, therapies. Areas covered: Mipomersen is an anti-sense oligonucleotide that prevents production of apolipoprotein B leading to decreased levels of very low-density lipoprotein (VLDL) and LDL. In this review the authors discuss the pharmacokinetics of the drug, the clinical trials evaluating its efficacy and safety, and risks and challenges associated with its clinical implementation. Its use as therapy for the treatment of FH is also discussed. Expert opinion: Mipomersen is approved for use only in homozygous FH. It has frequent adverse effects, such as injection site reactions, flu-like symptoms, and hepatoxicity. It is useful only in patients who have failed other therapies, and it faces competition from other medications that have more tolerable side effect profiles.
Topics: Animals; Anticholesteremic Agents; Apolipoproteins B; Atherosclerosis; Cholesterol, LDL; Humans; Hyperlipoproteinemia Type II; Oligonucleotides
PubMed: 30526168
DOI: 10.1080/14656566.2018.1550071 -
Advances in Nutrition (Bethesda, Md.) Sep 2023Cardiovascular disease (CVD) is the leading cause of death globally. Habitual consumption of tree nuts and peanuts is associated with cardioprotective benefits.... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular disease (CVD) is the leading cause of death globally. Habitual consumption of tree nuts and peanuts is associated with cardioprotective benefits. Food-based dietary guidelines globally recommend nuts as a key component of a healthy diet. This systematic review and meta-analysis were conducted to examine the relationship between tree nut and peanut consumption and risk factors for CVD in randomized controlled trials (RCTs) (PROSPERO: CRD42022309156). MEDLINE, PubMed, CINAHL, and Cochrane Central databases were searched up to 26 September, 2021. All RCT studies that assessed the effects of tree nut or peanut consumption of any dose on CVD risk factors were included. Review Manager software was used to conduct a random effect meta-analysis for CVD outcomes from RCTs. Forest plots were generated for each outcome, between-study heterogeneity was estimated using the I test statistic and funnel plots and Egger's test for outcomes with ≥10 strata. The quality assessment used the Health Canada Quality Appraisal Tool, and the certainty of the evidence was assessed using grading of recommendations assessment, development, and evaluation (GRADE). A total of 153 articles describing 139 studies (81 parallel design and 58 cross-over design) were included in the systematic review, with 129 studies in the meta-analysis. The meta-analysis showed a significant decrease for low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglycerides (TG), TC:high-density lipoprotein (HDL) cholesterol, LDL cholesterol:HDL cholesterol, and apolipoprotein B (apoB) following nut consumption. However, the quality of evidence was "low" for only 18 intervention studies. The certainty of the body of evidence for TC:HDL cholesterol, LDL cholesterol:HDL cholesterol, and apoB were "moderate" because of inconsistency, for TG were "low," and for LDL cholesterol and TC were "very low" because of inconsistency and the likelihood of publication bias. The findings of this review provide evidence of a combined effect of tree nuts and peanuts on a range of biomarkers to create an overall CVD risk reduction.
Topics: Humans; Cardiovascular Diseases; Nuts; Arachis; Cholesterol, LDL; Cholesterol, HDL; Randomized Controlled Trials as Topic; Cholesterol; Triglycerides; Apolipoproteins B
PubMed: 37149262
DOI: 10.1016/j.advnut.2023.05.004 -
Nutrients Mar 2022Osteoarthritis (OA) imposes an increasing social burden due to global activity limitations, especially among the aged. Links between circulating lipids and OA have been...
Osteoarthritis (OA) imposes an increasing social burden due to global activity limitations, especially among the aged. Links between circulating lipids and OA have been reported; however, confounding data from observational studies have hindered causal conclusions. We used Mendelian randomization (MR) approach to evaluate the genetic causal effects of circulating apolipoproteins and lipoprotein lipids on OA risk. Genetic instruments at the genome-wide significance level (p < 5 × 10−8) were selected from genome-wide association studies (n = 393,193−441,016 individuals). Summary-level OA data were obtained from the UK Biobank (39,427 cases, 378,169 controls). Bidirectional two-sample Mendelian randomization (MR) analyses used MR-Egger, weighted median, and MR-PRESSO for sensitivity analysis. Genetic predisposition to 1-SD increments of Apolipoprotein B (APOB), and low-density lipoprotein (LDL) was associated with a decreased risk of knee or hip OA (KHOA) (odds ratio (OR) = 0.925, 95% confidence interval (95% CI): 0.881−0.972, p = 0.002; OR = 0.898, 95% CI: 0.843−0.957, p = 0.001) and hip OA (HOA) (OR = 0.894; 95% CI: 0.832−0.961, p = 0.002; OR = 0.870 95% CI: 0.797−0.949, p = 0.002). Genetically predicted APOB showed an association with knee OA (KOA) (OR per SD increase, 0.930, 95% CI: 0.876−0.987, p = 0.016). The OR of KOA was 0.899 (95% CI: 0.835−0.968, p = 0.005) for a 1-SD increase in LDL. Apolipoprotein A1, high-density lipoprotein, and triglycerides showed no association. Inverse MR showed no causal effect of KOA, HOA, or KHOA on these serum lipids. Distinct protective genetic-influence patterns were observed for APOB and LDL on OA, offering new insights into relationships between lipids and OA risk and a better understanding of OA etiology.
Topics: Aged; Apolipoprotein B-100; Apolipoproteins B; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Osteoarthritis, Hip; Osteoarthritis, Knee; Polymorphism, Single Nucleotide; Triglycerides
PubMed: 35405941
DOI: 10.3390/nu14071327 -
Molecular and Cellular Endocrinology Dec 2019Lipids play a critical role in energy metabolism, and a suite of proteins is required to deliver lipids to tissues. Several of these proteins require an intricate... (Review)
Review
Lipids play a critical role in energy metabolism, and a suite of proteins is required to deliver lipids to tissues. Several of these proteins require an intricate endoplasmic reticulum (ER) quality control (QC) system and unique secondary chaperones for folding. Key examples include apolipoprotein B (apoB), which is the primary scaffold for many lipoproteins, dimeric lipases, which hydrolyze triglycerides from circulating lipoproteins, and the low-density lipoprotein receptor (LDLR), which clears cholesterol-rich lipoproteins from the circulation. ApoB requires specialized proteins for lipidation, dimeric lipases lipoprotein lipase (LPL) and hepatic lipase (HL) require a transmembrane maturation factor for secretion, and the LDLR requires several specialized, domain-specific chaperones. Deleterious mutations in these proteins or their chaperones may result in dyslipidemias, which are detrimental to human health. Here, we review the ER quality control systems that ensure secretion of apoB, LPL, HL, and LDLR with a focus on the specialized chaperones required by each protein.
Topics: Apolipoproteins B; Cholesterol; Endoplasmic Reticulum; Humans; Lipids; Lipoprotein Lipase; Lipoproteins; Molecular Chaperones; Quality Control; Receptors, LDL
PubMed: 31442546
DOI: 10.1016/j.mce.2019.110547 -
Indian Heart Journal Mar 2024This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a... (Review)
Review
This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a predictor of atherosclerotic cardiovascular disease and recommendations of (inter)national treatment guidelines regarding Apo B in dyslipidemia management. A single Apo B molecule is present in every particle of very low-density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and lipoprotein(a). This unique single Apo B per particle ratio makes plasma Apo B concentration a direct measure of the number of circulating atherogenic lipoproteins. This review of global evidence on Apo B as a biomarker for atherosclerosis confirms that Apo B is a single atherogenic lipid marker present in all lipids sub-fractions except HDL-C, and thus, Apo B integrates and extends the information from triglycerides and cholesterol, which could simplify and improve care for atherosclerotic cardiovascular disease.
Topics: Humans; Apolipoproteins B; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Triglycerides
PubMed: 38599726
DOI: 10.1016/j.ihj.2023.12.001 -
Frontiers in Endocrinology 2023This study aims to evaluate the effect of acupuncture on the emotion domain and metabolic parameters of Chinese women with polycystic ovarian syndrome (PCOS) by... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aims to evaluate the effect of acupuncture on the emotion domain and metabolic parameters of Chinese women with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomized clinical trial, conducted from 6 July 2012 to 7 October 2015.
METHOD
In this study, we investigated the effects of acupuncture (458 patients) and sham acupuncture (468 patients) on metabolic parameters, serum ions, and all quality-of-life scale scores related to PCOS. The quality of life of patients was evaluated using five relevant scales, operated by the research assistant, namely, PCOSQ, SF-36, and ChiQOL, as well as Zung-SAS and Zung-SDS. Metabolic parameters and serum ions were measured.
RESULTS
A reduction in acne score, AN, Hcy, and LDL-C, and an increase in the level of lipoprotein α, Apo A1, and Apo A1/Apo B were observed in the acupuncture group after 4 months' intervention after adjusting clomiphene and reproductive outcome (< 0.05). An increase in SF-36 total scores, RP and RE scores, ChiQOL total scores, and emotion domain scores was observed in the acupuncture group after 4 months' intervention, while PF and HT scores were decreased (adjusted < 0.05). Those same changes were observed in sham acupuncture. Meanwhile, the serum levels of Ca, K, and Cl were elevated in the acupuncture group after the interventions (adjusted < 0.005). There were no significant differences in HOMA-IR, MetS, FPG, FINS, HDL-C, TG, Apo B, and level of serum P, Mg, and Na. Also, no changes in BP, GH, VT, SF, physical form domain, and spirit domain were observed after treatment.
CONCLUSION
Acupuncture can improve not only the emotional changes in SF-36 scores and ChiQOL scores, but also lipid metabolism, implying that it may have a correlation between emotional change and lipid metabolism. Furthermore, acupuncture can also regulate the changes of serum Ca, K, and Cl.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT01573858.
Topics: Humans; Female; Apolipoprotein A-I; Polycystic Ovary Syndrome; Quality of Life; Acupuncture Therapy; Apolipoproteins B; Emotions
PubMed: 37711905
DOI: 10.3389/fendo.2023.1237260 -
Nature Genetics Feb 2023APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the...
APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues. Crypts with SBS2/SBS13 often had immediate crypt neighbors without SBS2/SBS13, suggesting that the underlying cause of SBS2/SBS13 is cell-intrinsic. APOBEC mutagenesis occurred in an episodic manner throughout the human lifespan, including in young children. APOBEC1 mRNA levels were very high in the small intestine epithelium, but low in the large intestine epithelium and other tissues. The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA.
Topics: Child; Humans; Child, Preschool; Apolipoproteins B; Cytidine Deaminase; Mutagenesis; RNA, Messenger; APOBEC-1 Deaminase; Intestine, Small
PubMed: 36702998
DOI: 10.1038/s41588-022-01296-5 -
Clinical Rheumatology Jun 2023Disturbed lipid metabolism was observed in systemic lupus erythematosus (SLE) patients. This study aimed to evaluate the relationships between dyslipidemia and visceral...
INTRODUCTION
Disturbed lipid metabolism was observed in systemic lupus erythematosus (SLE) patients. This study aimed to evaluate the relationships between dyslipidemia and visceral organ involvement, disease severity, inflammatory factors, and drug intake in SLE patients.
METHOD
Inpatients with SLE (n = 105) and healthy controls (HC) (n = 75) were recruited in this study. Clinical and laboratory data were collected from patient records. The concentrations of tumor necrosis factor receptors superfamily member1A (TNFRSF1A), member1B (TNFRSF1B) and adipokine angiopoietin-like 4 (ANGPTL4) in plasma were measured by ELISA.
RESULT
Compared to HC, serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and apolipoprotein B (ApoB) were significantly increased, while high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) were decreased in SLE patients. Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters were closely correlated with serum lipid levels. Inflammatory factors were associated with dyslipidemia. The levels of TNFRSF1A and TNFRSF1B were obviously increased and associated with kidney involvement in SLE patients. Patients with high-dose glucocorticoid intake showed more severe dyslipidemia.
CONCLUSIONS
Attention should be paid to the dyslipidemia of SLE. Dyslipidemia is associated with inflammation and organ involvement in SLE. These findings might provide a new strategy for the treatment of SLE. Key Points • Serum levels of TG, TC, LDL, and ApoB were significantly increased, while HDL and ApoA1 were decreased in SLE patients. • Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters and inflammatory factors were closely correlated with serum lipid levels. • Patients with high-dose glucocorticoid intake showed more severe dyslipidemia. • These findings might provide a new strategy for the treatment of SLE.
Topics: Humans; Glucocorticoids; Triglycerides; Lipoproteins, HDL; Inflammation; Lupus Erythematosus, Systemic; Dyslipidemias; Apolipoproteins B
PubMed: 36790644
DOI: 10.1007/s10067-023-06539-2 -
Pharmacological Research Sep 2023The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and...
The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.
Topics: Humans; Apolipoproteins B; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Risk Assessment; Triglycerides
PubMed: 37517561
DOI: 10.1016/j.phrs.2023.106873 -
Journal of Atherosclerosis and... May 2016Familial hypercholesterolemia (FH) is the most common autosomal disorder characterized by an elevated low-density lipoprotein-cholesterol level and a high risk of... (Review)
Review
Familial hypercholesterolemia (FH) is the most common autosomal disorder characterized by an elevated low-density lipoprotein-cholesterol level and a high risk of premature cardiovascular disease. In this review, we summarize information on FH studies in Asian countries, focusing on mean cholesterol level, FH frequency, diagnostic criteria, genotypes, and clinical care of FH patients in Asian populations. Compared with Western countries, most Asian countries had lower mean cholesterol levels, with a significant variation between different countries. In the limited studies reported, a frequency of 1/900 was reported in Hokuriku district, Japan in 1977 and a frequency of 1/85 among Christian Lebanese in 1979. Recently, a population study in China reported frequencies of 0.47% and 0.28%. However, the different FH frequencies reported were based on different diagnostic criteria. Of 28 publications from 16 Asian countries or regions, 14 used self-defined FH criteria. Only one specific guideline for FH was available, which was developed by Japanese scientists. Six Asian countries joined the Make Early Diagnosis to Prevent Early Deaths program in the late 1990s, and the estimated diagnosis rates of FH ranged from 3% to 10% in these countries. A more recent study explored the awareness, knowledge, and perception of FH among practitioners in Japan, Korea, and Taiwan. The study found that the correct rates of these FH-related questions were low and concluded that lack of country-specific criteria and guidelines may contribute to the lack of FH knowledge in the present survey. More attention and resources should be focused on raising awareness, improving care, and increasing FH research in Asian populations.
Topics: Alleles; Apolipoproteins B; Asian People; China; Genetic Predisposition to Disease; Genotype; Humans; Hyperlipoproteinemia Type II; Japan; Lebanon; Mutation; Proprotein Convertase 9; Receptors, LDL; Republic of Korea; Taiwan
PubMed: 27075771
DOI: 10.5551/jat.34405