Circulating ACE2: a novel biomarker of cardiovascular risk.
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ABSTRACT:
SUBMITTER: Ramchand J
PROVIDER: S-EPMC7529379 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Endothelial dysfunction is involved in several cardiovascular diseases. Elevated levels of circulating endothelial cells (CECs) and low levels of endothelial progenitor cells (EPCs) have been described in different cardiovascular conditions, suggesting their potential use as diagnostic biomarkers for endothelial dysfunction. Compared to typical peripheral blood leukocyte subsets, CECs and EPCs occur at very low frequency. The reliable identification and characterization of CECs and EPCs is a prerequisite for their clinical use, however, a validated method to this purpose is still missing but a key for rare cell events. Objectives:To establish a validated flow cytometric procedure in order to quantify CECs and EPCs in human whole blood. Methods:In the establishment phase, the assay sensitivity, robustness, and the sample storage conditions were optimized as prerequisite for clinical use. In a second phase, CECs and EPCs were analyzed in heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction, in arterial hypertension (aHT), and in diabetic nephropathy (DN) in comparison to age-matched healthy controls. Results:The quantification procedure for CECs and EPCs showed high sensitivity and reproducibility. CEC values resulted significantly increased in patients with DN and HFpEF in comparison to healthy controls. CEC quantification showed a diagnostic sensitivity of 90% and a sensitivity of 68.0%, 70.4%, and 66.7% for DN, HFpEF, and aHT, respectively. Conclusion:A robust and precise assay to quantify CECs and EPCs in pre-clinical and clinical studies has been established. CEC counts resulted to be a good diagnostic biomarker for DN and HFpEF.
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Project description:Current clinical guidelines emphasize the unmet need for technological innovations to guide physician decision-making and to transit from conventional care to personalized cardiovascular medicine. Biomarker-guided cardiovascular therapy represents an interesting approach to inform tailored treatment selection and monitor ongoing efficacy. However, results from previous publications cast some doubts about the clinical applicability of biomarkers to direct individualized treatment. In recent years, the non-coding human transcriptome has emerged as a new opportunity for the development of novel therapeutic strategies and biomarker discovery. Non-coding RNA (ncRNA) signatures may provide an accurate molecular fingerprint of patient phenotypes and capture levels of information that could complement traditional markers and established clinical variables. Importantly, ncRNAs have been identified in body fluids and their concentrations change with physiology and pathology, thus representing promising non-invasive biomarkers. Previous publications highlight the translational applicability of circulating ncRNAs for diagnosis and prognostic stratification within cardiology. Numerous independent studies have also evaluated the potential of the circulating non-coding transcriptome to predict and monitor response to cardiovascular treatment. However, this field has not been reviewed in detail. Here, we discuss the state-of-the-art research into circulating ncRNAs, specifically microRNAs and long non-coding RNAs, to support clinical decision-making in cardiovascular therapy. Furthermore, we summarize current methodological and conceptual limitations and propose future steps for their incorporation into personalized cardiology. Despite the lack of robust population-based studies and technical barriers, circulating ncRNAs emerge as a promising tool for biomarker-guided therapy.
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Project description:Fibroblast growth factor-23 (FGF)-23 is a phosphaturic hormone involved in mineral bone metabolism that helps control phosphate homeostasis and reduces 1,25-dihydroxyvitamin D synthesis. Recent data have highlighted the relevant direct FGF-23 effects on the myocardium, and high plasma levels of FGF-23 have been associated with adverse cardiovascular outcomes in humans, such as heart failure and arrhythmias. Therefore, FGF-23 has emerged as a novel biomarker of cardiovascular risk in the last decade. Indeed, experimental data suggest FGF-23 as a direct mediator of cardiac hypertrophy development, cardiac fibrosis and cardiac dysfunction via specific myocardial FGF receptor (FGFR) activation. Therefore, the FGF-23/FGFR pathway might be a suitable therapeutic target for reducing the deleterious effects of FGF-23 on the cardiovascular system. More research is needed to fully understand the intracellular FGF-23-dependent mechanisms, clarify the downstream pathways and identify which could be the most appropriate targets for better therapeutic intervention. This review updates the current knowledge on both clinical and experimental studies and highlights the evidence linking FGF-23 to cardiovascular events. The aim of this review is to establish the specific role of FGF-23 in the heart, its detrimental effects on cardiac tissue and the possible new therapeutic opportunities to block these effects.
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Project description:Background Low-grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high-sensitivity CRP (C-reactive protein). Methods and Results A total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4±0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1±5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross-sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9-to-10-year follow-up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within-subject correlation over 9-to-10-year follow-up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle-related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow-mediated dilation=-1.2 [-1.8, -0.7]% per z-score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], ≈1.1 per z-score increase for both cohorts) and metabolic syndrome (RR, ≈1.2-1.3 per z-score increase for both cohorts) in 9-to-10-year follow-up. Conclusions Low-grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10-year follow-up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.
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Project description:Context:Mitochondrial DNA mutations and dysfunction are associated with prostate cancer (PCa). Small humanin-like peptide-2 (SHLP2) is a novel mitochondrial-encoded peptide and an important mitochondrial retrograde signaling molecule. Objective:To determine whether serum SHLP2 concentration is associated with PCa risk and whether associations are race-specific.Design, Setting and Participants: Patients undergoing prostate biopsy were recruited from the Durham Veterans Affairs hospital. Serum was collected prior to biopsy and SHLP2 measured by ELISA. We selected 200 men for analysis (100 negative biopsies and 100 PCa cases; 100 black and 100 white). Results:Mean SHLP2 levels were significantly higher in white controls versus black controls and SHLP2 was significantly higher in white controls versus white PCa cases. In contrast, there was no significant difference in SHLP2 levels between black controls and black cases. SHLP2 levels > 350-pg/ml ruled out PCa with ≥ 95% accuracy in both races. Conclusions:Lower SHLP2 was linked with increased PCa risk in white men, but no significant association was observed in black men. While SHLP2 > 350-pg/ml ruled out PCa in both races with high accuracy, SHLP2 was unrelated to PCa grade. These data suggest the circulating mitochondrial-derived peptide hormone, SHLP2 plays a key role in the development and racial disparity of prostate cancer.
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Project description:Glycosylated proteins partake in multiple cellular processes including inflammation. We hypothesized that GlycA, a novel biomarker of protein glycan N-acetyl groups, is related to incident cardiovascular disease (CVD), and we compared it with high-sensitivity C-reactive protein (hsCRP).In 27 491 initially healthy women, baseline GlycA was quantified by nuclear magnetic resonance spectroscopy and hsCRP by an immunoturbidimetric assay. During median follow-up of 17.2 years, 1648 incident CVD events occurred (myocardial infarction, ischemic stroke, coronary revascularization, and CVD death). GlycA and hsCRP were moderately correlated (Spearman r=0.61, P<0.0001). In Cox regression models that included age, ethnicity, smoking, blood pressure, medications, menopausal status, body mass index, and diabetes, hazard ratios for CVD across quartiles 1 to 4 of GlycA were 1.00, 1.10 (95% CI, 0.92 to 1.30), 1.34 (95% CI, 1.13 to 1.58), and 1.64 (95% CI, 1.39 to 1.93), similar to hsCRP, for which hazard ratios were 1.00, 1.18 (95% CI, 0.99 to 1.41), 1.35 (95% CI, 1.14 to 1.61), and 1.75 (95% CI, 1.47 to 2.09) (both Ptrend<0.0001). Associations were attenuated after additionally adjusting for lipids: the hazard ratio of quartile 4 versus 1 for GlycA was 1.23 (95% CI, 1.04 to 1.46; Ptrend=0.002) and for hsCRP was 1.44 (95% CI, 1.20 to 1.72; Ptrend<0.0001). Further adjustment for the other biomarker resulted in a hazard ratio of quartile 4 versus 1 for GlycA of 1.03 (95% CI, 0.85 to 1.24; Ptrend=0.41) and for hsCRP of 1.29 (95% CI, 1.06 to 1.56; Ptrend=0.001).In this prospective study of initially healthy women, baseline GlycA was associated with incident CVD, consistent with a possible role for protein glycans in inflammation and CVD.http//clinicaltrials.gov/. Unique identifier NCT00000479.
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Project description:Cardiovascular disease (CVD) is the leading cause of death globally. Risk assessment is crucial for identifying at-risk individuals who require immediate attention as well as to guide the intensity of medical therapy to reduce subsequent risk of CVD. In the past decade, many risk prediction models have been proposed to estimate the risk of developing CVD. However, in patients with a history of CVD, the current models that based on traditional risk factors provide limited power in predicting recurrent cardiovascular events. Several biomarkers from different pathophysiological pathways have been identified to predict cardiovascular events, and the incorporation of biomarkers into risk assessment may contribute to enhance risk stratification in secondary prevention. This review focuses on biomarkers related to cardiovascular and metabolic diseases, including B-type natriuretic peptide, high-sensitivity cardiac troponin I, adiponectin, adipocyte fatty acid-binding protein, heart-type fatty acid-binding protein, lipocalin-2, fibroblast growth factor 19 and 21, retinol-binding protein 4, plasminogen activator inhibitor-1, 25-hydroxyvitamin D, and proprotein convertase subtilisin/kexin type 9, and discusses the potential utility of these biomarkers in cardiovascular risk prediction among patients with CVD. Many of these biomarkers have shown promise in improving risk prediction of CVD. Further research is needed to assess the validity of biomarker and whether the strategy for incorporating biomarker into clinical practice may help to optimize decision-making and therapeutic management.
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Project description:We sought to identify circulating microRNAs (miRNAs) from blood plasma that could be used as biomarkers to detect breast cancer existing in high-risk benign breast tumors. Plasma samples were collected from patients with early-stage breast cancer (CA), high- (HB), moderate- (MB), and no-risk (Be) benign tumors. The miRNAs we have identified have the potential to develop into a crucial blood-based screening tool to help monitor the development of breast cancer in benign breast tumors.
2023-04-20 | GSE225117 | GEO
Project description:BACKGROUND:Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D. METHODS:275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS:ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P?<?0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P?<?0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P?<?0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P?<?0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P?<?0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS)???50% (both P?<?0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P?<?0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P?<?0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P?<?0.05). CONCLUSION:ACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.
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Project description:Microarrays with 1,205 human microRNAs and 142 viral microRNAs were used for screening candidate diagnostic markers in the 3 categories of subjects from 24 plasma samples including acute aortic dissection, healthy and aortic aneurysm subjects. There were two microRNAs overlapping in the 3 group comparisons. Finally, 16 candidate microRNAs discovered via microarrays were selected for the further validation.
2017-11-15 | GSE92427 | GEO