Cardiovascular Disease Biomarkers Research Articles

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.

Redox-signalling and Redox Biomarkers in Cardiovascular Health and Disease.

Overproduction of reactive nitrogen and oxygen species (RNS and ROS) has been linked to the pathogenesis of diabetes, hypertension, hyperlipidemia, stroke, angina, and other cardiovascular diseases. These species are produced in part by the mitochondrial respiratory chain, NADPH oxidase, and xanthine oxidase. RNS and ROS both contribute to oxidative stress, which is necessary for the development of cardiovascular disorders. In addition to ROS species like hydroxyl ion, hydrogen peroxide, and superoxide anion, RNS species like nitric oxide, peroxynitrous acid, peroxynitrite, and nitrogen dioxide radicals have also been linked to a number of cardiovascular conditions. They promote endothelial dysfunction, vascular inflammation, lipid peroxidation, and oxidative damage, all of which contribute to the development of cardiovascular pathologies. It's crucial to understand the mechanisms that result in the production of RNS and ROS in order to identify potential therapeutic targets. Redox biomarkers serve as indicators of oxidative stress, making them crucial tools for diagnosing and predicting cardiovascular states. The advancements in proteomics, metabolomics, genomics, and transcriptomics have made the identification and detection of these small molecules possible. The following redox biomarkers are notable examples: 3-nitrotyrosine, 4-hydroxy-2-nonenal, 8- iso-prostaglandin F2, 8-hydroxy-2-deoxyguanosine, malondialdehyde, Diacron reactive oxygen metabolites, total thiol, and specific microRNAs (e.g. miRNA199, miRNA21, miRNA1254, miRNA1306-5p, miRNA26b-5p, and miRNA660-5p) are examples. Although redox biomarkers have great potential, their clinical applicability faces challenges. Redox biomarkers frequently have a short half-life and exist in small quantities in the blood, making them challenging to identify and measure. The interpretation of biomarker data may also be influenced by confounding factors and the complex interplay of various oxidative stress pathways. Therefore, in-depth validation studies and the development of sensitive and precise detection methods are needed to address these problems. In the search for redox biomarkers, cutting-edge techniques like mass spectrometry, immunoassays, and molecular diagnostics are applied. New platforms and technologies have made it possible to accurately detect and monitor redox biomarkers, which facilitates their use in clinical settings. Our expanding knowledge of RNS and ROS involvement in cardiovascular disorders has made it possible to develop redox biomarkers as diagnostic and prognostic tools. Overcoming the challenges associated with their utility and utilizing advanced detection techniques, which will improve their clinical applicability, will ultimately benefit the management and treatment of cardiovascular conditions.

Systemic immune- inflammation index predicts post-MI left ventricular remodeling.

Previous studies demonstrated that remodeling after successful percutaneous coronary intervention (PCI) depends on the inflammatory response triggered by myocardial infarction (MI). The systemic immune-inflammation index (SII) is a novel inflammation index strongly associated with coronary artery disease. In our study, we sought to determine whether SII could predict Post-MI LV remodeling. The study population included 528 patients (mean age 62.5 ± 10.2, 73% male) diagnosed with STEMI. Based on the increase in LVEDV within the first 12 months after STEMI, patients were divided into two groups. We categorized the ≥ 20% increase in LVEDV among remodelers (257 patients, 49%), and the other 271 patients (51%), as non-remodelers. To determine the relationship between laboratory parameters and LV remodeling, univariate and multivariate logistic regression models were used. In a univariate model, higher hs-CRP and SII values were associated with increased LVEDV. In a multivariate analysis, SII independently correlated with LV remodeling A cut-off value of 613.3 or higher for SII was significantly correlated with LV remodeling based on ROC analysis. SII provides an easy-to-calculate and affordable biomarker for cardiovascular diseases. It may be used as a new biomarker to predict LV remodeling in patients with STEMI.

Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells

BackgroundCoronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases.MethodsSerum exosomes from patients with DM, DM with coronary microvascular dysfunction (DM-CMD) or DM with coronary artery disease (DM-CAD) were extracted for miRNA sequencing. The expression of miR-16-2-3p was assessed in high glucose-treated human aortic endothelial cells and human cardiac microvascular endothelial cells. Fluorescence in situ hybridization (FISH) was used to detect miR-16-2-3p within the myocardium of db/db mice. Intramyocardial injection of lentivirus overexpressing miR-16-2-3p was used to explore the function of the resulting gene in vivo. Bioinformatic analysis and in vitro assays were carried out to explore the downstream function and mechanism of miR-16-2-3p. Wound healing and tube formation assays were used to explore the effect of miR-16-2-3p on endothelial cell function.ResultsmiR-16-2-3p was upregulated in circulating exosomes from DM-CMD, high glucose-treated human cardiac microvascular endothelial cells and the hearts of db/db mice. Cardiac miR-16-2-3p overexpression improved cardiac systolic and diastolic function and coronary microvascular reperfusion. In vitro experiments revealed that miR-16-2-3p could regulate fatty acid degradation in endothelial cells, and ACADM was identified as a potential downstream target. MiR-16-2-3p increased cell migration and tube formation in microvascular endothelial cells.ConclusionsOur findings suggest that circulating miR-16-2-3p may serve as a biomarker for individuals with DM-CMD. Additionally, miR-16-2-3p appears to alleviate coronary microvascular dysfunction in diabetes by modulating ACADM-mediated fatty acid degradation in endothelial cells.

Circulating Myokines as Novel Biomarkers for Cardiovascular Diseases

Circulating Myokines as Novel Biomarkers for Cardiovascular Diseases

Soluble ST2 and its relation to inflammatory, vascular atherosclerotic, and calcification markers in patients with atrial fibrillation or heart failure at moderate-to-high cardiovascular risk

Background: Cardiovascular diseases (CVDs) are the major cause of death globally. Among them, heart failure (HF) and atrial fibrillation (AF) result in poor prognosis and quality of life. Standard methods for assessing AF and HF, through history and physical examination, have limited sensitivity and specificity, which lead to delayed diagnosis and high risk of mortality. The identification of biomarkers able to detect the early stages of disease and/or their progression is of great importance for improving the clinical outcome. As AF and HF often coexist, it would be of great importance to find a biomarker with diagnostic utility in predicting HF in AF patients. Soluble suppression of tumorigenesis-2 (sST2) is a part of the cardioprotective IL-33/ST2 signaling pathway and may serve as a candidate biomarker for HF and AF. We aimed to evaluate sST2 serum levels in patients with AF and HF with preserved ejection fraction (HFpEF) and to explore potential relationships with traditional CVD risk factors and with novel biomarkers for vascular calcification such as undercarboxylated matrix Gla-protein (ucMGP). Materials and Methods: This study included 99 patients stratified into three groups: HFpEF (n=19), paroxysmal or persistent AF in sinus rhythm (n=33), and control group without CVD but at moderate-to-high CVD risk (n=47). Hemodynamic and anthropometric measures, coronary artery calcification (CAC), routine laboratory parameters, circulating ucMGP, and sST2 were measured. Results: sST2 levels were highly elevated in HFpEF patients. Significant positive correlation was found between sST2 and CAC-score (r=0.237, p=0.039), negative relations with serum lipids in AF patients, and positive association with serum C-reactive protein (r=0.609, p=0.018) in HFpEF patients. Soluble ST2 positively correlates with ucMGP in the entire studied population (r=0.252, p=0.006) and in the combined CVD group (AF+HFpEF) (r=0.254, p=0.036). Conclusions: sST2 levels emerge as a novel biomarker in CVD and may have prognostic importance for HF prediction in AF patients.

Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes

ObjectivesGlycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D. MethodsGlomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.0 years of age, 50% female, glycated hemoglobin 8.7±1.3%, T1D duration 5.7±2.6 years). Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. ResultsGlycA's were higher in girls vs boys (1.05±0.26 vs 0.84±0.15 mmol/L, p=0.001) and in participants living with overweight/obesity vs normal weight (1.12±0.23 vs 0.87±0.20 mmol/L, p=0.0004). GlycA's correlated positively with estimated intraglomerular pressure (r=0.52, p=0.001), UACR (r=0.53, p<0.0001), and trunk mass (r=0.45, p=0.001), and inversely with estimated insulin sensitivity (r=−0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and glycated hemoglobin. ConclusionsAs biomarker of inflammation, GlycA's were higher in girls and those with overweight or obese body habitus in T1D. GlycA's associated with parameters of early kidney dysfunction, central adiposity, and insulin resistance.

Correlation of circulatory VEGF and miRNA 126 in angiographically proven coronary artery disease and its clinical importance

Background: Atherosclerotic ischemic coronary artery disease (CAD) is a major cause of morbidity and mortality in both developed and developing countries, indicating the need for the discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Vascular endothelial growth factor (VEGF) may have some role, in the progression of human coronary atherosclerosis. Circulating microRNAs (miR) have a potential as a diagnostic as well as a prognostic biomarker of cardiovascular disease and dysfunctions. Aims and Objectives: The aim of the study was to correlate the levels of miRNA-126 and VEGF in the serum of CAD patients. Materials and Methods: The study was conducted on 100 cases of freshly diagnosed CAD patients (angiographically proven) and 80 normal healthy patients. Various serum biomarkers were estimated. The level of serum VEGF and Mi-RNA was correlated for CAD patients. Results: Highly significantly difference was found in levels of hemoglobin A1C, low density lipoprotein, total cholesterol, and total homocysteine while high-density lipoproteins and triglycerides were less significantly different for controls and cases. VEGF levels of CAD cases were found to be very significantly higher as compared to controls. The miRNA-126 expression was found to be lower in the CAD subjects compared to non-CAD subjects. Conclusion: The study was suggested the role of VEGF in atherogenesis and plaque instability. No significant correlation was found among between miR-126 levels and VEGF levels among CAD cases. The study is limited by a smaller sample size and was single-centered; therefore, multicentric study with a larger patient cohort needs to be done and to validate our findings.

Mice, rats, and guinea pigs differ in FMOs expression and tissue concentration of TMAO, a gut bacteria-derived biomarker of cardiovascular and metabolic diseases.

Increased plasma trimethylamine oxide (TMAO) is observed in cardiovascular and metabolic diseases, originating from the gut microbiota product, trimethylamine (TMA), via flavin-containing monooxygenases (FMOs)-dependent oxidation. Numerous studies have investigated the association between plasma TMAO and various pathologies, yet limited knowledge exists regarding tissue concentrations of TMAO, TMAO precursors, and interspecies variability. Chromatography coupled with mass spectrometry was employed to evaluate tissue concentrations of TMAO and its precursors in adult male mice, rats, and guinea pigs. FMO mRNA and protein levels were assessed through PCR and Western blot, respectively. Plasma TMAO levels were similar among the studied species. However, significant differences in tissue concentrations of TMAO were observed between mice, rats, and guinea pigs. The rat renal medulla exhibited the highest TMAO concentration, while the lowest was found in the mouse liver. Mice demonstrated significantly higher plasma TMA concentrations compared to rats and guinea pigs, with the highest TMA concentration found in the mouse renal medulla and the lowest in the rat lungs. FMO5 exhibited the highest expression in mouse liver, while FMO3 was highly expressed in rats. Guinea pigs displayed low expression of FMOs in this tissue. Despite similar plasma TMAO levels, mice, rats, and guinea pigs exhibited significant differences in tissue concentrations of TMA, TMAO, and FMO expression. These interspecies variations should be considered in the design and interpretation of experimental studies. Furthermore, these findings may suggest a diverse importance of the TMAO pathway in the physiology of the evaluated species.

Dietary Insulin Index (DII) and Dietary Insulin load (DIL) and Caveolin gene variant interaction on cardiometabolic risk factors among overweight and obese women: a cross-sectional study

Background and objectiveStudies have shown that Caveolin gene polymorphisms (CAV-1) are involved in chronic diseases, such as metabolic syndrome. Moreover, the dietary insulin index (DII) and dietary insulin load (DIL) have been shown to potentially elicit favorable effects on cardiovascular disease (CVD) risk. Therefore, this study sought to investigate the effect of DII DIL and CAV-1 interaction on CVD risk factors.MethodsThis cross-sectional study consisted of 333 overweight and obese women aged 18–48 years. Dietary intakes, DII, and DIL were evaluated using the 147-item food frequency questionnaire (FFQ). Serum profiles were measured by standard protocols. The CAV-1 rs 3,807,992 and anthropometric data were measured by the PCR–RFLP method and bioelectrical impedance analysis (BIA), respectively. Participants were also divided into three groups based on DII, DIL score, and rs3807992 genotype.ResultsThis comparative cross-sectional study was conducted on 333 women classified as overweight or obese. Participants with A allele for the caveolin genotype and higher DII score showed significant interactions with high-density lipoprotein (HDL) (P for AA = 0.006 and P for AG = 0.019) and CRI-I (P for AA < 0.001 and P for AG = 0.024). In participants with AA genotype and greater DII score, interactions were observed in weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, CRI-II, fat-free mass (FFM), and skeletal muscle mass (SMM) (P < 0.079). Those with higher DIL scores and AA genotype had higher weight (P = 0.033), FFM (P = 0.022), and SMM (P = 0.024). In addition, DIL interactions for waist/hip ratio (WHR), waist circumference (WC), triglyceride (TG), CRI-I, and body fat mass (BFM) among individuals with AA genotype, while an HDL interaction was observed in individuals with AG and AA (P < 0.066).ConclusionThe findings of the present study indicate that people who carry the caveolin rs3807992 (A) allele and have greater DII and DIL scores are at higher risk for several cardiovascular disease and metabolic syndrome biomarkers. These results highlight that diet, gene variants, and their interaction, should be considered in the risk evaluation of developing CVD.

Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives.

Overall diet, lifestyle choices, genetic predisposition, and other underlying health conditions may contribute to higher trimethylamine N-oxide (TMAO) levels and increased cardiovascular risk. This review explores the potential therapeutic ability of RSV to protect against cardiovascular diseases (CVD) and affect TMAO levels. This review considers recent studies on the association of TMAO with CVD. It also examines the sources, mechanisms, and metabolism of TMAO along with TMAO-induced cardiovascular events. Plant polyphenolic compounds, including resveratrol (RSV), and their cardioprotective mechanism of regulating TMAO levels and modifying gut microbiota are also discussed here. RSV's salient features and bioactive properties in reducing CVD have been evaluated. The close relationship between TMAO and CVD is clearly understood from currently available data, making it a potent biomarker for CVD. Precise investigation, including clinical trials, must be performed to understand RSV's mechanism, dose, effects, and derivatives as a cardioprotectant agent.

Anti-Obesity Effect of Combining White Kidney Bean Extract, Propolis Ethanolic Extract and CrPi3 on Sprague-Dawley Rats Fed a High-Fat Diet.

Obesity has been associated with the occurrence and prevalence of various chronic metabolic diseases. The management of obesity has evolved to focus not only on reducing weight, but also on preventing obesity-related complications. Studies have shown that bioactive components in natural products like white kidney bean extract (WKBE), propolis ethanolic extract (PEE), and chromium picolinate (CrPi3) showed anti-obesity properties. However, no studies have examined the outcomes of combining any of these nutraceutical supplements. We compared the effects of HFD supplemented with WKBE, WKBE+PEE, or WKBE+PEE+CrPi3 against control and obese groups using Sprague-Dawley rats fed a 45% high-fat diet as an in vivo model. Nutritional parameters, biochemical parameters, and biomarkers of cardiovascular disease, liver function, kidney function, and gut health were among the comparable effects. Our findings showed that combining the three nutraceutical supplements had a synergetic effect on reducing weight gain, food utilization rate, abdominal fat, serum lipids, arterial and hepatic lipids, risk of cardiovascular disease, and blood glucose level, in addition to improving renal function and gut microbiota. We attributed these effects to the α-amylase inhibitor action of WKBE, flavonoids, and polyphenol content of PEE, which were potentiated with CrPi3 resulting in a further reduction or normalization of certain parameters.

Role of miRNA in Cardiovascular Diseases in Children-Systematic Review.

The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the genetic factors and molecular mechanisms related to the pathogenesis of CVDs in order to develop new prevention and treatment strategies for the future. MicroRNAs (miRNAs) constitute a class of small non-coding RNA fragments that range from 17 to 25 nucleotides in length and play an essential role in regulating gene expression, controlling an abundance of biological aspects of cell life, such as proliferation, differentiation, and apoptosis, thus affecting immune response, stem cell growth, ageing and haematopoiesis. In recent years, the concept of miRNAs as diagnostic markers allowing discrimination between healthy individuals and those affected by CVDs entered the purview of academic debate. In this review, we aimed to systematise available information regarding miRNAs associated with arrhythmias, cardiomyopathies, myocarditis and congenital heart diseases in children. We focused on the targeted genes and metabolic pathways influenced by those particular miRNAs, and finally, tried to determine the future of miRNAs as novel biomarkers of CVD.

Association of PCSK-9 with the Biomarkers of Type-2 Diabetes and its Complications in the Indian Population: a Pilot Study.

Proprotein convertase subtilisin/kexin type-9 (PCSK-9) is a serine protease with profound effects on plasma LDL-C, the major risk factor for cardiovascular diseases (CVDs). However, plasma PCSK-9 level and its association with the biomarkers of CVDs, diabetes, and associated complications have not yet been reported in the northeastern population of India. Of the total cohort (n = 233), we analyzed healthy controls (HC; n = 50), freshly diagnosed type-2-diabetes mellitus (T2DM-FD; n = 46), T2DM treated (T2DM-T; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemia (T2DM-DL; n = 45) subjects. Plasma PCSK-9 and other biological determinants associated with T2DM, CVD, and nephrotic dysfunction were assessed. The level of plasma PCSK-9 in HC, T2DM-FD, T2DM-T, T2DM-N, and T2DM-DL groups was found to be 184.1 ± 13.83, 183.1 ± 24.4.3, 241.8 ± 75.42, 403.7 ± 85.94, and 641.3 ± 135.5 ng/mL, respectively, indicating its role in the severity of the here-mentioned complications. Moreover, plasma PCSK-9 levels further showed a significant correlation with the biomarkers of hyperglycemia, particularly HbA1c, as well as LDL-C in T2DM-FD, T2DM-N, and T2DM-DL subjects of the Indian population, while moderate association in T2DM-T subjects. Our first-of-its-kind clinical study aiming to quantify the circulatory PCSK-9 level in the Indian population concluded that elevated PCSK-9 was significantly associated with the severity of diabetes and associated complications. Moreover, such elevation in PCSK-9 might be attributed to the lipid- and glucoselowering medication-induced SREBP-2-dependent mechanisms. Since our conclusion is based on a pilot study, further cohort studies in larger populations of India are required to get a generalization regarding the role of PCSK-9 in DM and associated complications.