Independent Risk Factor For Atherosclerosis Research Articles

Exosomal miR-155-5p promote the occurrence of carotid atherosclerosis.

Periodontitis is a significant independent risk factor for atherosclerosis. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the effect of exosomes-miR-155-5p derived from periodontal endothelial cells on atherosclerosis invitro and invivo. Higher expression of miR-155-5p was detected in the plasma exosomes of patients with chronic periodontitis (CP) and carotid atherosclerosis (CAS) compared to patients with CP. Also, the expression level of miR-155-5p was associated with the severity of CP. miR-155-5p-enriched exosomes from HUVECs increased the angiogenesis and permeability of HAECs and promoted the expression of angiogenesis, permeability, and inflammation genes. Along with the overexpression or inhibition of miR-155-5p, the biological effect of HUVECs-derived exosomes on HAECs changed correspondingly. In ApoE-/- mouse models, miR-155-5p-enriched exosomes promoted the occurrence of carotid atherosclerosis by increasing permeable and angiogenic activity. Collectively, these findings highlight a molecular mechanism of periodontitis in CAS, uncovering exosomal miR-155-5p derived periodontitis affecting carotid endothelial cells in an 'exosomecrine' manner. Exosomal miR-155-5p may be used as a biomarker and target for clinical intervention to control this intractable disease in future, and the graphic abstract was shown in FigureS1.

Does the LPA genotype have a role in coronary artery disease risk beyond Lp(a) values?

Abstract Introduction High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for coronary artery disease (CAD). Many functional single nucleotide polymorphisms (SNPs) of the LPA gene have pronounced effects on Lp(a) concentrations. Studies show that rs3798220 polymorphism is strongly associated with Lp(a) concentration and also with risk of CAD. Goal: To evaluate if LPA rs3798220 T>C is associated with CAD beyond its effect on Lp(a) levels. Methods We performed a case-control study with 3,157 individuals (1,721 CAD patents and 1,436 controls). The LPA rs3798220 T>C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This variant has a minor allele frequency (MAF) <2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Laboratory analysis was performed, and Lp(a) biochemical levels were measured in the cases and controls. Chi-squared tests were used to determine differences by genotype in CAD association (in cases and controls). We also reported a multivariate logistic regression to test if this LPA variant is still independently associated with CAD after adjustment to Lp(a) levels and traditional risk factors for CAD. Results Wild-type genotype TT was increased in the group without CAD, whereas the genotype TC was higher in patients with CAD (p<0.0001). After multivariate logistic regression, adjusted for traditional risk factors, the TC genotype remained in the equation as an independent risk factor for CAD (OR=2.36; 95%CI: 1.54–3.61; p<0.0001). When the multivariate regression analysis is adjusted for traditional risk factors plus Lp(a) levels, the TC genotype remains in the equation as independently associated with CAD despite being substantially attenuated (OR=1.67; 95%CI: 1.07–2.60; p=0.025). Conclusion LPA rs3798220 T>C may be an independent risk factor for CAD beyond the effect of rising Lp(a) levels. Perhaps testing for the genetic determinants of Lp(a) relative to direct measurement of Lp(a) level could provide additional prognostic utility.

Causal association between visceral fat and coronary artery disease: a large-scale mendelian randomization analysis

Abstract Background While increased body mass index (BMI) is an established risk factor, the residual risk associated with visceral fat, remains a concern. We aimed to perform a Mendelian randomization to explore the causal relationship between visceral fat and the risk of coronary artery disease (CAD), aiming to address gaps left by observational studies that may be influenced by confounding factors and reverse causation. Methods Leveraging large-scale genome-wide association study (GWAS) databases, we identified single-nucleotide polymorphisms (SNPs) associated with visceral fat. These genetic instruments were analyzed to infer causal relationships with CAD outcomes, drawing data from the CARDIoGRAMplusC4D consortium for CAD, and additional databases for related cardiovascular conditions. We performed a Two-sample Mendelian Randomization (MR) to test the genetic association between the visceral obesity and Coronary Artery Disease (CAD). Results The analysis encompassed data from a combined cohort exceeding 500,000 participants, revealing a significant causal relationship between increased levels of visceral fat and the risk of CAD. The observed odds ratio (OR) for CAD per standard deviation (SD) increase in visceral fat was [OR, 1.48 ] ([95% CI, 1.33-1.64]; P<0.001), indicating a robust association which remains independent from BMI on mediation analysis. Notably, the study's methodology ensured minimal risk of pleiotropy, reinforcing the validity of the findings. Conclusions This Mendelian randomization study provides compelling evidence of a genetic causal link between visceral fat and coronary artery disease. The findings suggest that beyond BMI, visceral fat represents a significant, independent risk factor for CAD, underscoring the importance of considering comprehensive lipid management in cardiovascular risk reduction strategies. Further research is warranted to explore potential mechanisms and therapeutic targets associated with visceral fat in the context of cardiovascular disease.

Serum BAFF level is associated with the presence and severity of coronary artery disease and acute myocardial infarction

ObjectiveThe aim of this study was to investigate the relationship between circulating levels of B cell activating factor (BAFF) and the presence and severity of coronary artery disease (CAD) and acute myocardial infarction (AMI) in humans, as its biological functions in this context remain unclear.MethodsSerum BAFF levels were measured in a cohort of 723 patients undergoing angiography, including 204 patients without CAD (control group), 220 patients with stable CAD (CAD group), and 299 patients with AMI (AMI group). Logistic regression analyses were used to assess the association between BAFF and CAD or AMI.ResultsSignificantly elevated levels of BAFF were observed in patients with CAD and AMI compared to the control group. Furthermore, BAFF levels exhibited a positive correlation with the SYNTAX score (r = 0.3002, P < 0.0001) and the GRACE score (r = 0.5684, P < 0.0001). Logistic regression analysis demonstrated that increased BAFF levels were an independent risk factor for CAD (adjusted OR 1.305, 95% CI 1.078–1.580) and AMI (adjusted OR 2.874, 95% CI 1.708–4.838) after adjusting for confounding variables. Additionally, elevated BAFF levels were significantly associated with a high GRACE score (GRACE score 155 to 319, adjusted OR 4.297, 95% CI 1.841–10.030). BAFF exhibited a sensitivity of 75.0% and specificity of 71.4% in differentiating CAD patients with a high SYNTAX score, and a sensitivity of 75.5% and specificity of 72.8% in identifying AMI patients with a high GRACE score.ConclusionCirculating BAFF levels serve as a valuable diagnostic marker for CAD and AMI. Elevated BAFF levels are associated with the presence and severity of these conditions, suggesting its potential as a clinically relevant biomarker in cardiovascular disease.

The mediating effect of TyG and its derived indices in the association between OSAHS and atherosclerosis in patients with T2DM.

Triglyceride-glucose index (TyG) and its derived indices which better reflect metabolic disturbances on atherosclerosis has not been reliably compared in patients with type 2 diabetes mellitus (T2DM). Besides, obstructive sleep apnea hypopnea syndrome (OSAHS), a driver of atherosclerosis (AS), can exacerbate metabolic disturbances strongly. The aim of this study is to explore the mediating effect of glycolipid metabolism on the association between OSAHS and arterial stiffness in T2DM patients. 154 T2DM patients were involved in this study and were split into two groups: T2DM and T2DM + AS. Logistic regression analysis determined the accurate effects of different factors on the AS of T2DM patients. The capacity of TyG and the indices it derives to predict AS was assessed using the receiver operating characteristic (ROC) curve. Mediation analysis was employed to investigate the mediating effect of TyG and its derived indices on the association between OSAHS and arterial stiffness in T2DM patients. OSAHS, TyG, and its derived indices were independent risk factors for AS in T2DM patients. Stratified by age, the hazardous effects of TyG and its derived indices remained significant in T2DM patients aged ≥ 50 years, but not in those aged < 50 years. In T2DM patients aged ≥ 50 years, the novel indices have a high predictive value for AS, with TyG-BMI exhibiting the largest AUC(AUC:0.788;95% CI:0.647 ∼ 0.928; P < 0.001). The mediation analysis results indicated that in T2DM patients aged ≥ 50 years, TyG, TyG-BMI, TyG-WC, and TyG-WHtR acted as potential mediators in the association between OSAHS and AS, with mediation effects of 33.42%, 48.2%, 37.7%, and 40.21%, respectively. However, there was no significant mediating effect observed in the younger patients. TyG and its derived indices are strongly correlated with AS in T2DM patients, of which TyG-BMI has the best predictive performance. Besides, OSAHS partially exerts its atherogenic effect through glucolipid metabolism disorder in the T2DM population aged ≥ 50 years, while it mainly exerts a direct atherogenic effect in patients aged < 50 years.

TMAO induces pyroptosis of vascular endothelial cells and atherosclerosis in ApoE−/− mice via MBOAT2-mediated endoplasmic reticulum stress

Trimethylamine N-oxide (TMAO), a metabolite produced by intestinal flora, is recognized as an independent risk factor for atherosclerosis and atherosclerotic cardiovascular diseases. However, the underlying mechanism remains poorly understood. Here, we showed that dietary TMAO supplementation accelerates atherosclerosis in ApoE−/− mice. Pyroptosis and the expression of phospholipid-modifying enzyme MBOAT2 were increased in endothelial cells within atherosclerotic lesions. Genetic upregulation of MBOAT2 via adeno-associated virus with endothelium-specific promoter results in increased atherosclerotic lesions in ApoE−/− mice. Mechanistically, the overexpression of MBOAT2 disrupted glycerophospholipid metabolism and induced endothelial cell pyroptosis in an Endoplasmic reticulum stress-dependent manner. These data reveal that TMAO promotes endothelial cell pyroptosis and the progression of atherosclerotic lesions through the upregulation of MBOAT2, indicating that MBOAT2 is a promising therapeutic target for atherosclerosis.

Catalpol inhibits HHcy-induced EndMT in endothelial cells by modulating ROS/NF-κB signaling

BackgroundHyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis (AS). Endothelial mesenchymal transition (EndMT) refers to the process in which endothelial cells lose endothelial cell morphology and characteristic gene expression, and acquire phenotypic characteristics and gene expression related to mesenchymal cells. Numerous studies have confirmed that EndMT is involved in the formation of atherosclerosis. Catalpol is one of the active components of Rehmannia, which has antioxidant, anti-inflammatory, anti-tumor, neuroprotective and other biological activities. Studies have shown that catalpol can reduce atherosclerotic plaque induced by high sugar or fat. However, the effect of catalpol on HHCY-induced EndMT is unclear.Methods and resultsIn vitro HHcy-treated primary human umbilical vein endothelial cells (HUVECs) were used to construct a cell model, and the antioxidants N-acetylcysteine (NAC) and catalase alcohol were administered. In vivo C57BL/6N mice were given a diet fed with 4.4% high methionine chow to construct a HHcy mice model and were treated with catalpol. The results showed that hhcy could induce morphological transformation of endothelial cells into mesenchymal cells, increase intracellular ROS content, up-regulate α-SMA, N-cadherin, p-p65 protein expression, down-regulate VE-cadherin, CD31 protein expression, induce pathological changes of aortic root endothelium, and increase aortic endothelial ROS content. Catalpol reversed these hhcy induced outcomes.ConclusionsCatalpol inhibits HHcy-induced EndMT, and the underlying mechanism may be related to the ROS/NF-κB signaling pathway. Catalpol may be a potential drug for the treatment of HHcy-related AS.

Novel long noncoding lncARF mediated hyperhomocysteinemia-induced atherosclerosis via autophagy inhibition in foam cells

IntroductionHomocysteine (Hcy) is well recognized to be an independent risk factor for atherosclerosis. Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis, while the underlying mechanisms of its involvement in Hcy induced-atherosclerosis remain largely unknown. ObjectivesThe primary aim of this study is to assess the role of lncARF (autophagy-related factor induced by Hcy) in Hcy induced-atherosclerosis and related mechanism. MethodsRNA sequencing of foam cells treated with Hcy revealed a novel specific long noncoding RNA called lncARF. Locked nucleic acid gapmeRs-mediated lncARF knockdown was used to explore the role of lncARF both in vivo and in vitro. Mass spectrometry, RNA pull-down and RNA immunoprecipitation (RIP) assays were employed to uncover a mechanistic role of lncARF. Mass array assay and chromatin immunoprecipitation (ChIP) were used to detect the transcriptional activation of lncARF mediated by transcription factor. Clinically, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of lncARF in atherosclerotic patients with hyperhomocysteinemia (HHcy). ResultsWe observed that the expression of lncARF was substantially upregulated in atherosclerotic plaques, and knockdown of lncARF decreased the formation of atherosclerotic lesions by promoting autophagy in foam cells. Mechanistically, lncARF physically binds to RRAGD and inhibits its ubiquitination, further activating the PI3K/Akt and MAPK signaling pathways. Moreover, in vitro experiments showed that transcription factor FosB inhibited the binding of DNMT1 at the lncARF promoter, leading to transcriptional activation through DNA hypomethylation. Clinically, lncARF expression was positively correlated with serum Hcy levels, and it could distinguish atherosclerotic patients with HHcy with a high area under the ROC curve, sensitivity and specificity. ConclusionsOur study highlights the mechanisms of lncARF in protecting against the development of atherosclerosis involving the epigenetic modifications and RRAGD/PI3K/Akt and RRAGD/MAPK signaling pathways, which may provide novel diagnostic biomarkers to improve atherosclerosis treatment.

Atherogenic Effect of Homocysteine, a Biomarker of Inflammation and Its Treatment.

Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B 6 and vitamin B 12 folic acid (vitamin B 9 ). Causes of HHcy include deficiency of vitamins B 6 , B 9 , and B 12 , genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B 6 , and vitamin B 12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B 6 , vitamin B 12 , omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.

Association between R2CHA2DS2-VASc score and three-vessel coronary artery disease in a large population at high cardiovascular risk.

Coronary artery disease (CAD), particularly three-vessel coronary disease (3VD), is the main cause of death in industrialized countries. Chronic kidney disease is an independent risk factor for CAD. The CHA2DS2-VASc score shows a good ability to predict CV events in high-risk population independently from atrial fibrillation. The aim of the present study was to evaluate the association between the R2CHA2DS2-VASc score and 3VD in a population of patients at high cardiovascular risk. Monocentric prospective study evaluated 1017 patients undergoing coronary angiography. The R2CHA2DS2-VASc score was obtained by adding 2 points to the CHA2DS2-VASc score in case of eGFR < 60ml/min/1.73m2. Coronary lesions causing ≥ 50% reduction of a major epicardial vessel diameter were considered significant. Patients were grouped based on R2CHA2DS2-VASc tertiles and according to the severity of CAD: 3VD vs No-3VD. The 3VD group showed significantly higher R2CHA2DS2-VASc score than the No-3VD group (4.20 ± 2.18 vs 3.36 ± 2.06, p < 0.001). The risk of 3VD increased by 21% for every 1-point increase in the score (OR 1.21; 95% CI 1.13-1.28, p < 0.001). The prevalence of 3VD was higher among patients belonging to higher tertiles of R2CHA2DS2-VASc (17.2% vs 26.7% vs 33.6% for first, second, and third tertile respectively, p < 0.001) with a risk more than doubled for the third tertile compared to the first one (OR 2.45; 95% CI 1.71-3.49, p < 0.001). The R2CHA2DS2-VASc score is independently associated with 3VD in patients at high cardiovascular risk. The score could be considered a useful tool for clinicians to identify patients who are at high risk of 3VD.

The Comparative Study of Serum Estrogen and Lipid Profile in Pre- and Post-menopausal Women as Atherosclerosis Risk Factors in Pakistan.

Menopausesignifies the eternal termination of menstruation in women as a consequence of ovarian action loss, typically occurring around the age of 51 years. Cardiovascular disease is the leading cause of death among post-menopausal women, which may be due to lower levels of estrogen and lipid profile. The present study was undertaken to evaluate serum estrogen and lipid profile status to assess the risk of atherosclerosis in both pre- and post-menopausal women. The objective of this study is to explorethe relationship between estrogen and lipid levels of women in pre- and post-menopausal stages. A comparative cross-sectional study was conducted at Railway General Hospital Rawalpindi. A total of 100 participants were included of which 50 were pre-menopausal and 50 were post-menopausal women. Laboratory examination and questionnaires from the study population were used for data collection. Through the enzymatic method, serum cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) were assessed. Serum very low-density lipoprotein (VLDL) levels were calculated via Friedwald's components VLDL=TG/5.0. An enzyme-linked immunosorbent assay kit was used for estrogen measurement. For statistical analysis, Student's t-test and the Pearson correlation test were used. Women after menopause have significantly high serum cholesterol, low-density lipoproteins, VLDLs, and triglycerides while HDL-c levels were significantly low (P<0.001). Levels of estrogen were low in post-menopausal females (P<0.001) as compared to menstruating women. Estrogen with HDL concentrations showed a positive correlation with an r value of 0.08556 while LDL levels showed a negative correlation with ar value of -0.26219. This comparative study explores the relationship between estrogen and lipid levels in pre- and post-menopausal women. Low estrogen with changed lipid variables was observed. Decreased cardiovascular protective HDL-c marks that menopause is a phase that acts as an independent risk factor for atherosclerosis.

Homocysteine concentration in coronary artery disease and severity of coronary lesions.

Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.

Identification of a functional missense variant in the matrix metallopeptidase 10 (MMP10) gene in two families with premature myocardial infarction

A positive family history is a major independent risk factor for atherosclerosis, and genetic variation is an important aspect of cardiovascular disease research. We identified a heterozygous missense variant p.L245P in the MMP10 gene in two families with premature myocardial infarction using whole-exome sequencing. The aim of this study was to investigate the consequences of this variant using in-silico and functional in-vitro assays. Molecular dynamics simulations were used to analyze protein interactions, calculate free binding energy, and measure the volume of the substrate-binding cleft of MMP10-TIMP1 models. The p.L245P variant showed an altered protein surface, different intra- and intermolecular interactions of MMP10-TIMP1, a lower total free binding energy between MMP10-TIMP1, and a volume-minimized substrate-binding cleft of MMP10 compared to the wild-type. For the functional assays, human THP-1 cells were transfected with plasmids containing MMP10 cDNA carrying the p.L245P and wild-type variant and differentiated into macrophages. Macrophage adhesion and migration assays were then conducted, and pro-inflammatory chemokine levels were evaluated. The p.L245P variant led to macrophages that were more adherent, less migratory, and secreted higher levels of the pro-inflammatory chemokines CXCL1 and CXCL8 than wild-type macrophages. Thus, the p.L245P variant in MMP10 may influence the pathogenesis of atherosclerosis in families with premature myocardial infarction by altering protein - protein interactions, macrophage adhesion and migration, and expression of pro-inflammatory chemokines, which may increase plaque rupture. These results could contribute to the development of selective MMP10 inhibitors and reduce the risk of atherosclerosis in families with a history of premature myocardial infarction.

The Impact of Medical Physical Training and a Structured Personalized Exercise Training Program on Hemodynamic Parameters and Arterial Stiffness in Pregnant Women.

In developed countries, heart disease is the primary cause of maternal mortality during pregnancy. Arterial stiffness, an independent risk factor for atherosclerosis and a predictor of cardiovascular complications, can be assessed using the augmentation index (AIx) and pulse wave velocity (PWV). In this prospective study, we aimed to evaluate diverse hemodynamic parameters and arterial stiffness in pregnant women before and after participating in a structured, personalized exercise training program. Forty healthy pregnant women, non-smokers, who agreed to participate daily for 12 weeks in a physical exercise training program under the supervision of a team made up of an obstetrician, a cardiologist, and a physiotherapist were included. Anthropometric characteristics, arterial function, and physical activity data were collected from the participants at two different time points: at the beginning of the exercise training program (T0) and at the end, after 12 weeks (T1). Upon conducting a statistical analysis, it was discovered that there were noteworthy disparities (p = 0.05) in body mass index, brachial AIx, systolic blood pressure, and pulse pressure values between the two time points. The regression analysis for the AIx brachial values and the PWVao values from Trim II (T0) and Trim III (T1) showed major differences between these two time points; the association between the AIx brachial values in the second and third trimesters of pregnancy revealed a strong direct significant correlation (p < 0.001), and the correlation between the PWVao values in the second (T0) and third trimester (T1) of pregnancy was weak and insignificant (p = 0.12). The findings of our study indicate that a personalized exercise training program positively impacts the physical and psychological well-being of pregnant women, leading to a reduction in PWV.

The Relationship Between Frank's Sign and Coronary Artery Disease: A Literature Review

Coronary Artery Disease (CAD) is one of the leading causes of death and a significant public health concern. Approaches to early diagnosis of individuals at risk for CAD have always been a subject of research. The Frank sign is one of these approaches. The Frank sign is an independent risk factor for CAD and can be used, especially in the diagnostic process, to identify individuals at risk in the early stages. However, more studies and more extensive series should further support this finding.

Roles of Single Nucleotide Polymorphisms of C3 Gene in Patients with Coronary Artery Disease.

This study aims to investigate the association between nine tag single nucleotide polymorphisms (SNPs) in the C3 gene locus and the risk of coronary artery disease (CAD) as well as lipid levels in the Chinese population, and to further explore the interactions between SNPs and environmental factors that may be associated with CAD risk. A case-control study was conducted to investigate the association between CAD and C3 gene polymorphisms in a hospital setting. The study consisted of 944 CAD patients with a mean age of 55.97 10.182 years and 897 non-CAD controls with a mean age of 55.94 9.162 years. There were 565 males and 288 females in the CAD group and 583 males and 314 females in the control group. TagSNPs in the C3 gene were identified by employing the improved multiplex ligation detection reaction (iMLDR) technique, and multifactor dimensionality reduction (MDR) analysis was utilized to investigate the C3 gene-environment and gene-gene interactions in relation to the risk of CAD. Results of the polymorphism study indicated that the CC genotype of rs7257062 was more frequent in the CAD group compared to the control group (10.9% vs 7.7%), with a statistically significant difference (p = 0.009). Moreover, the TT and CC + CT genotype groups of rs7257062 in the CAD subgroup showed a significant difference in terms of serum triglyceride levels (2.326 1.889 vs 2.059 1.447, p = 0.019). Analysis of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) levels revealed no significant differences between the TT and CC + CT genotypes. Furthermore, no significant differences in serum lipid levels were observed between genotypes of the other SNPs. Multivariable logistic analysis, controlling for gender, age, body mass index (BMI), triglycerides (TG), TC, HDL-C, LDL-C, ApoA and ApoB, demonstrated that rs7257062 was still an independent risk factor of CAD (OR = 1.499, 95% CI: 1.036-2.168, p = 0.032). MDR analysis revealed that the rs7257062 interacted significantly with environmental factors such as smoking, diabetes, hypertension, BMI, and TG (p 0.05). The rs7257062 variation of the C3 gene could be linked to both lipid balance and the risk of CAD. It is conceivable that the interplay between C3 polymorphisms and environmental elements could account for the etiology of CAD.

The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers

Background and aimsCurrent research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD).MethodsThe study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics.ResultsPatients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (β = 0.86, P < 0.001) and WBC (β = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients.ConclusionOur research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.

Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.

Lipid metabolism related factors, such as angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non-CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor-α (TNF-α) levels were estimated using the enzyme-linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. The serum TNF-α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non-CAD groups (p < .05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p < .05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD.

Associations of the triglyceride-glucose index and remnant cholesterol with coronary artery disease: a retrospective study

BackgroundRemnant cholesterol (RC) represents a low-cost and readily measured lipid index that contributes significantly to residual cardiovascular disease risk. The triglyceride-glucose (TyG) index exhibits a significant correlation with cardiovascular disease occurrence. However, RC and the TyG index have rarely been examined for their potentials in predicting coronary artery disease (CAD). Accordingly, the study was designed to validate the correlations of these two biomarkers with CAD and to compare the forecasted values of these two biomarkers for newly diagnosed CAD.MethodsTotally 570 subjects firstly administered coronary angiography were enrolled, including 431 newly diagnosed CAD cases and 139 individuals without CAD. The individuals were classified into two groups according to CAD diagnosis. RC was derived as total cholesterol content (mmol/L) – (high density lipoprotein cholesterol content + low density lipoprotein cholesterol content; both in mmol/L). The TyG index was determined as ln (fasting triglyceride level [mg/dL] × fasting plasma glucose level [mg/dL])/2.ResultsBaseline feature analysis revealed significant differences in RC and the TyG index between the CAD and non-CAD groups (both P < 0.001). RC and the TyG index were independent risk factors for CAD in accordance with logistic regression analysis (both P < 0.05). Moreover, spearman correlation analysis elucidated CAD had a more remarkable correlation with the TyG index compared with RC (both P < 0.001). Furthermore, according to receiver operating characteristic curve analysis, the TyG index was better than RC in predicting CAD.ConclusionsThe TyG index and RC have significant associations with CAD. Compared with RC, the TyG index possesses a closer correlation with CAD and a higher predictive value for CAD.

Diet-Induced Severe Hyperhomocysteinemia Promotes Atherosclerosis Progression and Dysregulates the Plasma Metabolome in Apolipoprotein-E-Deficient Mice.

Atherosclerosis and resulting cardiovascular disease are the leading causes of death in the US. Hyperhomocysteinemia (HHcy), or the accumulation of the intermediate amino acid homocysteine, is an independent risk factor for atherosclerosis, but the intricate biological processes mediating this effect remain elusive. Several factors regulate homocysteine levels, including the activity of several enzymes and adequate levels of their coenzymes, including pyridoxal phosphate (vitamin B6), folate (vitamin B9), and methylcobalamin (vitamin B12). To better understand the biological influence of HHcy on the development and progression of atherosclerosis, apolipoprotein-E-deficient (apoE-/- mice), a model for human atherosclerosis, were fed a hyperhomocysteinemic diet (low in methyl donors and B vitamins) (HHD) or a control diet (CD). After eight weeks, the plasma, aorta, and liver were collected to quantify methylation metabolites, while plasma was also used for a broad targeted metabolomic analysis. Aortic plaque burden in the brachiocephalic artery (BCA) was quantified via 14T magnetic resonance imaging (MRI). A severe accumulation of plasma and hepatic homocysteine and an increased BCA plaque burden were observed, thus confirming the atherogenic effect of the HHD. Moreover, a decreased methylation capacity in the plasma and aorta, indirectly assessed by the ratio of S-adenosylmethionine to S-adenosylhomocysteine (SAM:SAH) was detected in HHD mice together with a 172-fold increase in aortic cystathionine levels, indicating increased flux through the transsulfuration pathway. Betaine and its metabolic precursor, choline, were significantly decreased in the livers of HHD mice versus CD mice. Widespread changes in the plasma metabolome of HHD mice versus CD animals were detected, including alterations in acylcarnitines, amino acids, bile acids, ceramides, sphingomyelins, triacylglycerol levels, and several indicators of dysfunctional lipid metabolism. This study confirms the relevance of severe HHcy in the progression of vascular plaque and suggests novel metabolic pathways implicated in the pathophysiology of atherosclerosis.