Cardiovascular Disease Biomarkers Research Articles

Circulating interleukin 17A and other inflammatory proteins may predict cardiovascular disease in early rheumatoid arthritis.

The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of cardiovascular disease (CVD) in patients with early RA. This study included consecutive patients with early RA recruited 1995-2002. Stored plasma samples were analyzed for 92 inflammatory proteins. CVD diagnoses were retrieved from national in-patient and cause-of-death registries. Statistical analyses were pre-designated as hypothesis-driven or exploratory. For the latter, proteins were selected based on principal component analysis (i.e., factor loading >0.5 within main components). Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. Data on baseline levels of proteins and CVD were available for 163 patients. As hypothesized, levels of IL-17A were associated with CVD [hazard ratio 1.35; 95% confidence interval 1.02-1.78, adjusted for age, sex, hypertension, diabetes, smoking and ESR], while not significantly with CAD. Osteoprotegerin (OPG) levels were significantly associated with both outcomes but only in crude models. No associations were observed for IL-6, TNF-α, monocyte chemotactic protein (MCP)-1 or IL-8. In the exploratory analyses, particularly MCP-3 had significant associations with both outcomes in crude models. Circulating IL-17A at RA diagnosis predicted future CVD, although we cannot exclude that this finding is due to multiple testing. The association was independent of traditional CVD risk factors, and of ESR at the time of diagnosis. Furthermore, OPG may be a predictor of CVD. We also identified some novel potential biomarkers for CVD in RA.

Levels of Small Extracellular Vesicles Containing hERG-1 and Hsp47 as Potential Biomarkers for Cardiovascular Diseases.

The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.

Serum Malondialdehyde-Modified Low-Density Lipoprotein as a Risk Marker for Peripheral Arterial Stiffness in Maintenance Hemodialysis Patients

Background and Objectives: Peripheral arterial stiffness (PAS), assessed by brachial-ankle pulse wave velocity (baPWV), is an independent biomarker of cardiovascular diseases (CVD) in patients on maintenance hemodialysis (HD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker, has been linked to atherosclerosis and CVD. However, the association between serum MDA-LDL and PAS among HD patients has not been fully elucidated. This study aimed to examine the association of serum MDA-LDL with PAS in HD patients and to identify the optimal cutoff value of serum MDA-LDL for predicting PAS. Materials and Methods: A cross-sectional study was conducted in 100 HD patients. Serum MDA-LDL was quantified using an enzyme-linked immunosorbent assay (ELISA), and baPWV was measured using a volume plethysmographic device. Patients were divided into the PAS group (baPWV > 18.0 m/s) and the non-PAS group (baPWV ≤ 18.0 m/s). The associations of baPWV and other clinical and biochemical parameters with serum MDA-LDL were assessed by multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of serum MDA-LDL for predicting PAS. Results: In multivariable logistic regression analysis, higher serum MDA-LDL, older age, and higher serum C-reactive protein [odds ratios (ORs) and 95% confidence intervals: 1.014 (1.004–1.025), 1.044 (1.004–1.085) and 3.697 (1.149–11.893)] were significantly associated with PAS. In the ROC curve analysis, the optimal cutoff value of MDA-LDL for predicting PAS was 80.91 mg/dL, with a sensitivity of 79.25% and a specificity of 59.57%. Conclusions: Greater serum MDA-LDL levels, particularly ≥80.91 mg/dL, were independently associated with PAS in HD patients. The findings suggest that oxidative stress plays a crucial role in the pathogenesis of PAS, and targeting MDA-LDL may be a potential therapeutic strategy for reducing cardiovascular risk in HD patients.

Platelet FcγRIIA: An emerging regulator and biomarker in cardiovascular disease and cancer

Platelets, anucleate blood cells derive from megakaryocytes, are involved in cardiovascular diseases and tumors. FcγRIIA, the only FcγR expressed on human platelets, is known for its role in immune-related diseases. A growing body of evidence reveals that platelet FcγRIIA is a potential target for the prevention and control of cardiovascular disease and cancer, and is an advantageous biomarker. In this review, we describe the structure and physiological function of platelet FcγRIIA, its regulatory role in cardiovascular disease and cancer, and its potential clinical application.

Proteomics validate circulating GDF-15 as an independent biomarker for COVID-19 severity.

Growth differentiation factor 15 (GDF-15) was originally described as a stress-induced cytokine, and a biomarker of aging and cardiovascular diseases. We hypothesized that circulating GDF-15 would be associated with COVID-19 disease severity. Herein, we explored this hypothesis in a large cohort of COVID-19 patients. Blood samples were collected from 926 COVID-19 adult patients and from 285 hospitalized controls from the Biobanque Québécoise de la COVID-19 (BQC19). COVID-19 severity was graded according to the WHO criteria. SOMAscan proteomics assay was performed on 50µL of plasma. ELISA were performed on 46 selected participants with left-over plasma to validate differences in plasma GDF-15 levels. Statistical analyses were conducted using GraphPad Prism 9.0 and SPSS. P values < 0.01 were considered significant. Proteomics showed that plasma GDF-15 levels were higher in COVID-19 patients compared to hospitalized controls. GDF-15 levels increased with COVID-19 severity. COVID-19 patients presenting with comorbidities including diabetes, cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease had higher GDF-15 levels. ELISA revealed significant elevation of GDF-15 until 30 days after hospitalization. Plasma GDF-15 elevation was correlated with older age. Moreover, GDF-15 levels correlated with pro-inflammatory cytokine interleukin-6 (IL-6) and inflammation marker C-reactive protein (CRP) as well as soluble levels of its putative receptor CD48. No association was established between anti-SARS-CoV-2 IgG levels and plasma GDF-15 levels. This study confirms GDF-15 as a biomarker for COVID-19 severity. Clinical evaluation of GDF-15 levels could assist identification of persons at high-risk of progressing to severe disease, thus improving patient care.

Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

Albumin-to-alkaline phosphatase ratio may be a better predictor of survival than sclerostin, dickkopf-1, osteopontin, osteoprotegerin and osteocalcin

ObjectivesThe value of biochemical markers of bone turnover (BTMs) in predicting survival and disease remains unclear. In a prospective study we evaluated the novel biomarkers for bone turnover sclerostin, dickkopf-1 (DKK-1), osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC), as well as a traditional biomarker, alkaline phosphatase (ALP) in relation to risk of mortality, cardiovascular events and fractures. Participantsand Methods:Routine blood tests and serum BTMs, including ALP, were analyzed in patients with hip fracture n=97, stroke n=71 and healthy volunteers n=83 (mean age 86, 83 and 77, respectively), followed for 7 years. Hazard Ratios (HR) were calculated for mortality, cardiovascular events and fractures in relation to these biomarkers. After adding the albumin-to-ALP ratio (AAPR) a post hoc analysis was performed. Results120 participants died during the study. In the entire group of patients and volunteers (n=251) higher AAPR (HR 0.28, 95 % CI 0.14 - 0.59, p<0.001) was associated with decreased mortality. OPN and OPG were associated with mortality risk only in the univariate statistical analysis. HR for high AAPR in relation to new cardiovascular events was borderline significant (HR 0.29, 95% CI 0.08 - 1.06, p= 0.061). None of the examined biomarkers were associated with new fractures, nor with an increased risk of a new cardiovascular event. ConclusionsAAPR may be a better predictor of mortality than the more novel BTMs, and higher AAPR could be associated with longer life expectancy. Further studies should determine the clinical usefulness of AAPR as a biomarker of mortality and cardiovascular disease.

Hybrid Bayesian Optimization-Based Graphical Discovery for Methylation Sites Prediction.

Protein methylation is one of the most important reversible post-translational modifications (PTMs), playing a vital role in the regulation of gene expression. Protein methylation sites serve as biomarkers in cardiovascular and pulmonary diseases, influencing various aspects of normal cell biology and pathogenesis. Nonetheless, the majority of existing computational methods for predicting protein methylation sites (PMSP) have been constructed based on protein sequences, with few methods leveraging the topological information of proteins. To address this issue, we propose an innovative framework for predicting Methylation Sites using Graphs (GraphMethySite) that employs graph convolution network in conjunction with Bayesian Optimization (BO) to automatically discover the graphical structure surrounding a candidate site and improve the predictive accuracy. In order to extract the most optimal subgraphs associated with methylation sites, we extend GraphMethySite by coupling it with a hybrid Bayesian optimization (together named GraphMethySite +) to determine and visualize the topological relevance among amino-acid residues. We evaluated our framework on two extended protein methylation datasets, and empirical results demonstrate that it outperforms existing state-of-the-art methylation prediction methods.

Association of cardiac biomarkers with long-term cardiovascular events in a community cohort

Introduction: We hypothesized that combining biomarkers of atherosclerotic cardiovascular disease (ASCVD) would improve prediction of ASCVD events in a primary prevention cohort. Materials and methods The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI). Results A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models. Discussion Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

Legumes and pulses - a scoping review for Nordic Nutrition Recommendations 2023.

Consumption of legumes and pulses is associated with various health outcomes. Therefore, when updating the Nordic Nutrition Recommendations (NNR), summarizing the best available evidence on key health outcomes regarded as relevant for the Nordic and Baltics related to the consumption of legumes was essential. The aim of this scoping review was to evaluate the updated evidence on the effect of the consumption of legumes and pulses on various health outcomes, as well as their dose-response relationship in updated systematic reviews and meta-analyses. The scoping review is built on a de novo systematic review published in 2023 and additional searches on the consumption of legumes and pulses and its various health outcomes, including cardiovascular disease (CVD), cancer, type 2 diabetes, and obesity. Current available evidence shows that the consumption of legumes and pulses is associated with a lower risk of several cancers (evidence: low-moderate), and lower all-cause mortality (evidence: moderate). The associations with CVDs are neutral or inverse, with studies generally showing favourable changes in biomarkers for CVDs. Legume consumption is associated with a lower risk of obesity (evidence: low). For type 2 diabetes, no association was found with incidence, but trials on consumption of legumes and pulses and biomarkers generally indicated protective effects. Overall, the current evidence supports dietary recommendations to increase the consumption of legumes and pulses.

Sensitive Electrochemical Biosensor Using Gold and Manganese (IV) Oxide Nanomaterials on Multiwalled Carbon Nanotubes for the Determination of Homocysteine With a Portable Potentiostat

Serum homocysteine (Hcy) is considered to be a reliable biomarker of cardiovascular, cerebrovascular and neurological diseases. Therefore, rapid, specific and sensitive measurement of homocysteine is crucial for prevention and diagnosis. Electrochemical methods, which benefit from simplicity, low-cost and quick response, have been widely utilized in the determination of targeted biomolecules. In this work, based upon a portable mini-potentiostat, a homocysteine electrochemical biosensor has been successfully developed combined with the modification of gold and manganese (IV) nanomaterials on multiwalled carbon nanotubes (MWCNTs) (denoted as Au@MnO2/MWCNTs) on screen-printed electrodes (SPEs). Due to the excellent electrochemical activity and catalytic capability of Au@MnO2/MWCNTs, the proposed electrochemical biosensor exhibited wide-linear range (5–125 μmol L−1), high sensitivity (0.01110 μA (μmol L−1)−1) and low detection limit (0.6173 μmol L−1) for homocysteine, requiring only 400 s to complete detection. It was effectively applied in the determination of serum homocysteine, and the results were consistent with those of an automated clinical chemistry analyzer. Furthermore, the simple and portable electrochemical device offers a promising manner for on-site analysis and home health monitoring.

Decreased circulating CTRP3 levels in acute and chronic cardiovascular patients

C1q/TNF-related protein 3 (CTRP3) represents an adipokine with various metabolic and immune-regulatory functions. While circulating CTRP3 has been proposed as a potential biomarker for cardiovascular disease (CVD), current data on CTRP3 regarding coronary artery disease (CAD) remains partially contradictory. This study aimed to investigate CTRP3 levels in chronic and acute settings such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS). A total of 206 patients were classified into three groups: CCS (n = 64), ACS having a first acute event (ACS-1, n = 75), and ACS having a recurrent acute event (ACS-2, n = 67). The control group consisted of 49 healthy individuals. ELISA measurement in peripheral blood revealed decreased CTRP3 levels in all patient groups (p < 0.001) without significant differences between the groups. This effect was exclusively observed in male patients. Females generally exhibited significantly higher CTRP3 plasma levels than males. ROC curve analysis in male patients revealed a valuable predictive potency of plasma CTRP3 in order to identify CAD patients, with a proposed cut-off value of 51.25 ng/mL. The sensitivity and specificity of prediction by CTRP3 were congruent for the subgroups of CCS, ACS-1, and ACS-2 patients. Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings, with male mice exhibiting higher circulating CTRP3 levels than females. We conclude that circulating CTRP3 levels are decreased in both male CCS and ACS patients. Therefore, CTRP3 might be useful as a biomarker for CAD but not for distinguishing an acute from a chronic setting.Key messagesCTRP3 levels were found to be decreased in both male CCS and ACS patients compared to healthy controls. Plasma CTRP3 has a valuable predictive potency in order to identify CAD patients among men and is therefore proposed as a biomarker for CAD but not for distinguishing between acute and chronic settings.Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings in men.

LncRNA H19: A Novel Biomarker in Cardiovascular Disease.

Cardiovascular disease is a major cause of death and disability worldwide. Recently, increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the pathogenesis of cardiovascular diseases, including atherosclerosis, coronary artery disease, dilated cardiomyopathy, diabetic cardiomyopathy, aortic dissection, and more. LncRNA H19 was the first to be described as a non-protein-coding mRNA-like molecule. A large number of studies have found that lncRNA H19 is related to the pathophysiological processes of cardiovascular diseases, and it is emerging as a potential key regulator of various heart diseases. In this review, we aim to summarize the role of lncRNA H19 in cardiovascular diseases in order to provide a theoretical basis for its potential use as a new therapeutic target in the future.

Fibroblast growth factor 23 during septic shock and myocardial injury in ICU patients

ObjectiveFibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular disease and is closely related to inflammation over the past decade. This study aimed to assess the relationship between FGF23 and myocardial injury in patients with sepsis. MethodsWe sequentially measured serum FGF23, Klotho, biomarkers of inflammation (CRP, IL-6 and WBC), myocardial injury (cTnI and N-terminal B-type natriuretic peptide) and sepsis (procalcitonin) at peak of intercurrent septic shock and after complete resolution or before death in a series of 29 patients with septic shock. 29 healthy adults without infections were used as controls. ResultsThere was a difference in serum FGF23 level between patients with septic shock and healthy adults (p < 0.0001), and the peak level of FGF23 in septic shock in the survivor group was higher than that after complete remission (p < 0.0001). No statistical difference was found in the level of FGF23 before and after treatment in the death group (p = 0.0947). At the peak of septic shock, FGF23 was significantly correlated with inflammatory markers, CRP (r = 0.8063, p < 0.0001), PCT (r = 0.6091, p = 0.0005) and WBC (r = 0.8312, p < 0.0001), while the correlation with IL-6 was not statistically significant (r = 0.0098, p = 0.9598). At the same time, it was found that FGF23 was significantly correlated with myocardial injury markers, cTNI (r = 0.8475, p < 0.0001) and NTproBNP (r = 0.8505, p < 0.0001). Nevertheless, FGF23 and klotho are not correlated (r = 0.2609, p = 0.1717). ConclusionIn conclusion, in patients with septic shock and myocardial injury, the exacerbation of inflammation in the septic process was accompanied by a abnormal increase of circulating FGF23 level. FGF23 also subsided after the improvement of inflammation, and the opposite was true for patients who did not survive. The up-regulation of FGF23 may be involved in the response of patients to septic shocks, and it is also speculated that FGF23 is involved in the myocardial injury of septic shock.

Antioxidant Vitamin Intake and LOX-Index in Japanese Municipal Workers.

Antioxidant vitamin intake has been reported to be associated with decreased risk of cardiovascular diseases. To date, however, no study has examined the association between antioxidant vitamin intake and LOX-index, a predictive biomarker of cardiovascular disease. We investigated the cross-sectional association between antioxidant vitamin (α-carotene, β-carotene, α-tocopherol, and vitamin C) intake and LOX-index in Japanese municipal workers. Participants were 346 workers (171 men and 175 women aged 19-71 y) who received a health check-up and participated in a nutrition and health survey. Antioxidant vitamin intake was assessed using a validated brief self-administered diet history questionnaire. LOX-index was calculated by multiplying serum concentrations of the soluble form of lectin-like oxidized LDL receptor 1 by those of LOX-1 ligands containing apolipoprotein B. Multiple regression analysis was used to estimate the geometric mean of LOX-index according to tertile of each antioxidant vitamin intake. Overall, α-carotene, β-carotene, α-tocopherol, and vitamin C intake were not associated with LOX-index. However, in stratified analyses by sex, geometric means of LOX-index tended to decrease with antioxidant vitamin intake in women, but not in men. The geometric means of LOX-index for the lowest through highest tertile of α-carotene intake were 771 (604-984), 639 (511-799), and 564 (469-677) (p for trend=0.07). Our results suggest that there is no association between antioxidant vitamin intake and LOX-index in Japanese workers. The suggestive inverse association between antioxidant vitamin intake and LOX-index in women warrants further investigation.

Trimethylamine N-Oxide as a Potential Biomarker for Cardiovascular Disease: Its Association with Dietary Sources of Trimethylamine N-Oxide and Microbiota

Trimethylamine N-Oxide as a Potential Biomarker for Cardiovascular Disease: Its Association with Dietary Sources of Trimethylamine N-Oxide and Microbiota

Sphingomyelins of Local Fat Depots and Blood Serum as Promising Biomarkers of Cardiovascular Diseases

Sphingomyelins of Local Fat Depots and Blood Serum as Promising Biomarkers of Cardiovascular Diseases

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

BackgroundVenous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE.MethodsThis observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was d-glutamine and d-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3′,5′-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68).ConclusionsOur findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.

Human soluble prorenin receptor expressed in mouse renal collecting duct shows sex-specific effect on cardiorenal function.

Soluble prorenin receptor (sPRR), a component of the renin-angiotensin system (RAS), has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. Despite studies showing that sPRR in the kidney is produced by tubular cells in the renal collecting duct (CD), its biological actions modulating cardiorenal function in physiological conditions remain unknown. Therefore, the objective of our study was to investigate whether CD-derived human sPRR (HsPRR) expression influences cardiorenal function and examine sex and circadian differences. Thus, we investigated the status of the intrarenal RAS, water and electrolyte balance, renal filtration capacity, and blood pressure (BP) regulation in CD-HsPRR and control (CTL) mice. CD-HsPRR mice were generated by breeding human sPRR-Myc-tag mice with Hoxb7/Cre mice. Renal sPRR expression increased in CD-HsPRR mice, but circulating sPRR and RAS levels were unchanged compared with CTL mice. Only female littermates expressing CD-HsPRR showed 1) increased 24-h BP, 2) an impaired BP response to an acute dose of losartan and attenuated angiotensin II (ANG II)-induced hypertension, 3) reduced angiotensin-converting enzyme activity and ANG II content in the renal cortex, and 4) decreased glomerular filtration rate, with no changes in natriuresis and kaliuresis despite upregulation of the β-subunit of the epithelial Na+ channel in the renal cortex. These cardiorenal alterations were displayed only during the active phase of the day. Taken together, these data suggest that HsPRR could interact with ANG II type 1 receptors mediating sex-specific, ANG II-independent renal dysfunction and a prohypertensive phenotype in a sex-specific manner.NEW & NOTEWORTHY We successfully generated a humanized mouse model that expresses human sPRR in the collecting duct. Collecting duct-derived human sPRR did not change circulating sPRR and RAS levels but increased daytime BP in female mice while showing an attenuated angiotensin II-dependent pressor response. These findings may aid in elucidating the mechanisms by which women show uncontrolled BP in response to antihypertensive treatments targeting the RAS, improving approaches to reduce uncontrolled BP and chronic kidney disease incidences in women.

Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1activity and Hcys with CVD.