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The Canadian Journal of Cardiology Apr 2024Plant-based meat alternatives (PBMAs) are highly processed food products that typically replace meat in the diet. In Canada, the growing demand for PBMAs coincides with... (Review)
Review
Plant-based meat alternatives (PBMAs) are highly processed food products that typically replace meat in the diet. In Canada, the growing demand for PBMAs coincides with public health recommendations to reduce ultra-processed food consumption, which prompts the need to investigate the long-term health implications of PBMAs. This review assesses the available literature on PBMAs and cardiovascular disease (CVD), including an evaluation of their nutritional profile and impact on CVD risk factors. Overall, the nutritional profiles of PBMAs vary considerably but generally align with recommendations for improving cardiovascular health; compared with meat, PBMAs are usually lower in saturated fat and higher in polyunsaturated fat and dietary fibre. Some dietary trials that have replaced meat with PBMAs have reported improvements in CVD risk factors, including total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B-100, and body weight. No currently available evidence suggests that the concerning aspects of PMBAs (eg, food processing and high sodium content) negate the potential cardiovascular benefits. We conclude that replacing meat with PBMAs may be cardioprotective; however, long-term randomised controlled trials and prospective cohort studies that evaluate CVD events (eg, myocardial infarction, stroke) are essential to draw more definitive conclusions.
PubMed: 38934982
DOI: 10.1016/j.cjca.2023.11.005 -
Journal of the American Heart... Jun 2024Atherosclerosis is triggered by the retention of apolipoprotein B-containing lipoproteins by proteoglycans. In addition to low-density lipoprotein, remnant lipoproteins...
Monoclonal Antibody chP3R99 Reduces Subendothelial Retention of Atherogenic Lipoproteins in Insulin-Resistant Rats: Acute Treatment Versus Long-Term Protection as an Idiotypic Vaccine for Atherosclerosis.
BACKGROUND
Atherosclerosis is triggered by the retention of apolipoprotein B-containing lipoproteins by proteoglycans. In addition to low-density lipoprotein, remnant lipoproteins have emerged as pivotal contributors to this pathology, particularly in the context of insulin resistance and diabetes. We have previously reported antiatherogenic properties of a monoclonal antibody (chP3R99) that recognizes sulfated glycosaminoglycans on arterial proteoglycans.
METHODS AND RESULTS
Solid-phase assays demonstrated that chP3R99 effectively blocked >50% lipoprotein binding to chondroitin sulfate and vascular extracellular matrix in vitro. The preperfusion of chP3R99 (competitive effect) resulted in specific antibody-arterial accumulation and reduced fluorescent lipoprotein retention by ~60% in insulin resistant JCR:LA- rats. This competitive reduction was dose dependent (25-250 μg/mL), effectively decreasing deposition of cholesterol associated with lipoproteins. In a 5-week vaccination study in insulin resistant rats with (200 μg subcutaneously, once a week), chP3R99 reduced arterial lipoprotein retention, and was associated with the production of antichondroitin sulfate antibodies (Ab3) able to accumulate in the arteries (dot-blot). Neither the intravenous inoculation of chP3R99 (4.5 mg/kg), nor the immunization with this antibody displayed adverse effects on lipid or glucose metabolism, insulin resistance, liver function, blood cell indices, or inflammation pathways in JCR:LA rats.
CONCLUSIONS
Both acute (passive) and long-term administration (idiotypic cascade) of chP3R99 antibody reduced low-density lipoprotein and remnant lipoprotein interaction with proteoglycans in an insulin-resistant setting. These findings support the innovative approach of targeting proatherogenic lipoprotein retention by chP3R99 as a passive therapy or as an idiotypic vaccine for atherosclerosis.
PubMed: 38934863
DOI: 10.1161/JAHA.123.032419 -
MSystems Jun 2024Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our...
Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., ), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.
PubMed: 38934598
DOI: 10.1128/msystems.00929-23 -
British Journal of Haematology Jun 2024Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence...
Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence in African SCA children. This prospective study included 600 steady-state SCA children aged 2-18 years from the Democratic Republic of Congo. Participants were genotyped for apolipoprotein L1 (APOL1) risk variants (RVs) and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. Kidney abnormalities were defined as albuminuria, hyperfiltration or decreased estimated creatinine-based glomerular filtration rate (eGFRcr). At baseline, 247/600 (41.2%) participants presented with kidney abnormalities: 82/592 (13.8%) with albuminuria, 184/587 (31.3%) with hyperfiltration and 15/587 (2.6%) with decreased eGFRcr. After a median follow-up of 5 months, repeated testing was performed in 180/247 (72.9%) available participants. Persistent hyperfiltration and persistent albuminuria (PA) were present in 29.2% (38/130) and 39.7% (23/58) respectively. eGFR normalized in all participants with a baseline decreased eGFRcr. Haemoglobinuria (p = 0.017) and male gender (p = 0.047) were significantly associated with PA and persistent hyperfiltration respectively. APOL1 RVs (G1G1/G2G2/G1G2) were borderline associated with PA (p = 0.075), while HMOX1 long repeat was not associated with any persistent kidney abnormality. This study reveals that a single screening can overestimate the rate of kidney abnormalities in children with SCA and could lead to overtreatment.
PubMed: 38934404
DOI: 10.1111/bjh.19603 -
Journal of Diabetes and Metabolic... Jun 2024Metabolic syndrome (MetS) is a constellation of coexisting cardiovascular risk factors. This study aimed to assess the evidence for the association between the... (Review)
Review
OBJECTIVES
Metabolic syndrome (MetS) is a constellation of coexisting cardiovascular risk factors. This study aimed to assess the evidence for the association between the apolipoprotein B/A1 ratio, apolipoprotein B, and apolipoprotein A1, and the MetS in children and adolescents.
METHODS
The English electronic databases including PubMed, Embase, Web of Science, and Scopus were searched up to February 28, 2022. To ascertain the validity of eligible studies, modified JBI scale was used. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using the random-effects model to evaluate the association between the apolipoprotein B/A1 ratio, apolipoprotein B, and apolipoprotein A1 and the MetS. Heterogeneity amongst the studies was determined by the use of the Galbraith diagram, Cochran's Q-test, and I test. Publication bias was assessed using Egger's and Begg's tests.
RESULTS
From 7356 records, 5 studies were included in the meta-analysis, representing a total number of 232 participants with MetS and 1320 participants as control group. The results indicated that increased levels of apolipoprotein B/A1 ratio (SMD 1.26; 95% CI: 1.04, 1.47) and apolipoprotein B (SMD 0.75; 95% CI: 0.36, 1.14) and decreased levels of apolipoprotein A1 (SMD -0.53; 95% CI: -0.69, -0.37) are linked to the presence of MetS. The notable findings were, children and adolescents with MetS had elevated levels of the apolipoprotein B/A1 ratio, apolipoprotein B, and decreased levels of apolipoprotein A1.
CONCLUSIONS
Our results suggest the need to evaluate the levels of apolipoproteins for detecting the risk of MetS in children and adolescents.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01235-z.
PubMed: 38932877
DOI: 10.1007/s40200-023-01235-z -
Medicina (Kaunas, Lithuania) Jun 2024Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2...
Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.
Topics: Humans; Diabetes Mellitus, Type 2; Pakistan; Male; Female; Apolipoproteins E; Middle Aged; Cardiovascular Diseases; Adult; Polymorphism, Genetic; Aged; Risk Factors; Dyslipidemias; Genotype; Stroke
PubMed: 38929578
DOI: 10.3390/medicina60060961 -
Genes May 2024Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes...
Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the gene, rs429358 and rs7412 for the gene and rs1801157 [-3'G(801)A] for gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the Q192R is likely to play a role as a risk factor for retinal vein occlusion.
Topics: Humans; Aryldialkylphosphatase; Retinal Vein Occlusion; Male; Female; Chemokine CXCL12; Case-Control Studies; Middle Aged; Polymorphism, Single Nucleotide; Aged; Apolipoproteins E; Genetic Predisposition to Disease; Risk Factors; Greece; Haplotypes
PubMed: 38927649
DOI: 10.3390/genes15060712 -
Biomedicines Jun 2024Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk... (Review)
Review
Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk factor for atherosclerotic cardiovascular disease, stroke, and aortic valve stenosis through multifactorial pathogenic mechanisms that include inflammation, atherogenesis, and thrombosis. Despite an estimated 20% of the global population having elevated lipoprotein(a) levels, testing remains underutilized due to poor awareness and a historical lack of effective and safe therapies. Although lipoprotein(a) has a strong association with coronary artery disease and cerebrovascular disease, its relationship with peripheral artery disease is less well established. In this article, we review the epidemiology, biology, and pathogenesis of lipoprotein(a) as it relates to peripheral artery disease. We also discuss emerging treatment options to help mitigate major adverse cardiac and limb events in this population.
PubMed: 38927436
DOI: 10.3390/biomedicines12061229 -
Biomedicines May 2024The cluster is an essential component in regulating lipoprotein metabolism and maintaining plasma lipid homeostasis. A genome-wide association analysis and Mendelian... (Review)
Review
The cluster is an essential component in regulating lipoprotein metabolism and maintaining plasma lipid homeostasis. A genome-wide association analysis and Mendelian randomization have revealed potential associations between genetic variants within this cluster and lipid metabolism disorders, including hyperlipidemia and cardiovascular events. An enhanced understanding of the complexity of gene regulation has led to growing recognition regarding the role of epigenetic variation in modulating gene expression. Intensive research into the epigenetic regulatory patterns of the cluster will help increase our understanding of the pathogenesis of lipid metabolism disorders and facilitate the development of new therapeutic approaches. This review discusses the biology of how the cluster affects circulating lipoproteins and the current progress in the epigenetic regulation of the cluster.
PubMed: 38927431
DOI: 10.3390/biomedicines12061224 -
Biomedicines May 2024Roux-en-Y gastric bypass (RYGB) is a treatment for severe obesity. However, many patients have insufficient total weight loss (TWL) after RYGB. Although multiple factors...
Roux-en-Y gastric bypass (RYGB) is a treatment for severe obesity. However, many patients have insufficient total weight loss (TWL) after RYGB. Although multiple factors have been involved, their influence is incompletely known. The aim of this exploratory study was to evaluate the feasibility and reliability of the use of machine learning (ML) techniques to estimate the success in weight loss after RYGP, based on clinical, anthropometric and biochemical data, in order to identify morbidly obese patients with poor weight responses. We retrospectively analyzed 118 patients, who underwent RYGB at the Hospital Clínico Universitario of Valencia (Spain) between 2013 and 2017. We applied a ML approach using local linear embedding (LLE) as a tool for the evaluation and classification of the main parameters in conjunction with evolutionary algorithms for the optimization and adjustment of the parameter model. The variables associated with one-year postoperative %TWL were obstructive sleep apnea, osteoarthritis, insulin treatment, preoperative weight, insulin resistance index, apolipoprotein A, uric acid, complement component 3, and vitamin B12. The model correctly classified 71.4% of subjects with TWL < 30% although 36.4% with TWL ≥ 30% were incorrectly classified as "unsuccessful procedures". The ML-model processed moderate discriminatory precision in the validation set. Thus, in severe obesity, ML-models can be useful to assist in the selection of patients before bariatric surgery.
PubMed: 38927382
DOI: 10.3390/biomedicines12061175