Clinical significance of plasma MMP‐2 and MMP‐9 levels as biomarkers for tumor expression in breast cancer patients in Egypt

Matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9) are involved in the breakdown of extracellular matrix in normal physiological processes as well as in disease processes, such as cancer metastasis. We conducted this work to study the role of MMP-2 and MMP-9 in breast cancer by measuring their plasma concentrations before and after surgery. Also, to examine if their levels can reflect the stage of disease and prognosis. Forty-eight breast cancer patients and 13 patients with benign breast diseases were included in the study. MMP-2 and MMP-9 levels were measured by ELISA and semi-quantitative real-time PCR. MMP-2 and MMP-9 levels in plasma were determined by ELISA immediately before surgery and during 6 to 12 months after curative surgery. We observed a significant increase in the level of MMP-9 mRNA expression in breast cancer patients in comparison to their normal breast tissues and to tissues of benign breast disease. In all TNM tumor stages, the plasma levels of MMP-2 and MMP-9 were increased significantly before curative surgery in the studied patients with breast carcinoma and decreased significantly after surgery. Both MMP-2 and MMP-9 may be used as a possible marker for follow-up or as a marker that reflects the response of the disease to treatment.

     

Plasma netrin-1 is a diagnostic biomarker of human cancers

Context:?The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues.

Objectives:?To determine whether plasma netrin-1 can be used as a diagnostic biomarker of human cancer.

Materials and Methods:?A total of 300 cancer plasma samples from breast, renal, prostate, liver, meningioma, pituitary adenoma, glioblastoma, lung, pancreatic and colon cancer patients were compared against 138 control plasma samples. Netrin-1 levels were quantified by ELISA and immunohistochemistry.

Results:?Plasma netrin-1 levels were significantly increased in breast, renal, prostate, liver, meningioma, pituitary adenoma, and glioblastoma cancers as compared to control samples.

Discussion and Conclusion:?Our results suggest that plasma netrin-1 can be used as a diagnostic biomarker for many human cancers.     

CXC chemokine ligand 4 (CXCL4) is predictor of tumour angiogenic activity and prognostic biomarker in non-small cell lung cancer (NSCLC) patients undergoing surgical treatment

Objective: To evaluate the association of CXC chemokine ligand 4 (CXCL4) plasma levels with tumour angiogenesis in non-small cell lung cancer (NSCLC) and to assess association of CXCL4 with clinical outcomes.

Patients and methods: Fifty patients with early stage NSCLC who underwent pulmonary resection. CXCL4 levels were analysed by ELISA. Angiogenesis was assessed by immunohistochemistry, and microvessel density (MVD) count.

Results: There was positive correlation between MVD and CXCL4 levels. Patients with higher CXCL4 levels had worse overall and disease-free survival.

Conclusions: Plasma levels of CXCL4 are associated with tumour vascularity. Increased CXCL4 levels in NSCLC patients undergoing treatment may indicate active cancer-induced angiogenesis associated with relapse and worse outcome.     

Metabolomic screening and star pattern recognition by urinary amino acid profile analysis from bladder cancer patients

Metabolomic analysis of urinary amino acids (AAs) from patients with bladder cancer was performed by gas chromatography–mass spectrometry. The β-aminoisobutyric acid (P < 0.05) and pyroglutamic acid (P < 0.03) levels among 21 AAs had relatively low P-values in the cancer group. The distorted star pattern of the cancer group was different from the heneicosagonal shape of the control mean. The present metabolomic screening combined with star pattern recognition method as clinical monitoring tool might be useful for the visual discrimination of bladder cancer group from normal group.     

肝癌疼痛与血浆VEGF、BDNF、FGF-2水平的相关性研究

目的:研究肝癌疼痛与血浆血管内皮生长因子(VEGF)、脑源性神经营养因子(BDNF)、纤维细胞生长因子-2(FGF-2)水平的相关性。方法:选择我院2018年10月～2019年7月收治的30例肝癌疼痛患者作为研究对象,依据疼痛程度分为4例轻度疼痛组、19例中度疼痛组、7例重度疼痛组,同期纳入30例肝癌无痛患者和30例健康对照组,比较各组血浆VEGF、BDNF和FGF-2水平,并分析肝癌疼痛患者血浆VEGF、BDNF和FGF-2水平和数字评分法(NRS)评分的相关性。结果:肝癌疼痛组血浆VEGF、BDNF、FGF-2水平显著高于肝癌无痛组及对照组(P0.05)。重度疼痛组血浆VEGF、BDNF、FGF-2水平显著高于中度疼痛组及轻度疼痛组(P0.05)。治疗后,肝癌疼痛患者血浆VEGF、BDNF、FGF-2水平显著低于治疗前(P0.05)。肝癌疼痛患者血浆VEGF、BDNF、FGF-2水平和NRS评分呈显著正相关(r值分别为0.619、0.571、0.563,P值均0.001)。结论:肝癌疼痛患者血浆VEGF、BDNF和FGF-2水平较肝癌无痛者明显上升,且和疼痛程度显著相关。     

Investigation of the relationship between GSTM1 gene variations and serum trace elements,plasma malondialdehyde levels in patients with colorectal cancer

Background

The aim of this study is to investigate of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patient with colorectal cancer.

Mateials and Methods.

Genotype distributions of GSTM1 gene variations were determined using real-time polymerase chain reaction method. Serum trace element levels were determined using atomic absorption spectrophotometer method and plasma MDA levels were measurement by spectrophotometric method.

Results

Serum Cu levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GA heterozygous genotype of the GSTM1 (rs 112,778,559) gene variation compared to healthy controls (p?<?0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in patients carrying GG homozygous genotype of the GSTM1 (rs 112778559) gene variation compared to healthy controls carrying same genotype (p?<?0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GG homozygous genotype of the GSTM1 (rs 12068997) gene variation compared to healthy controls (p?<?0.05). On the other hand, serum Se levels were detected significantly lower in CRC patients carrying GA heterozygous and GG homozygous genotypes for GSTM1 (rs 112,778,559) and (rs 12,068,997) gene variations compared to healthy controls (p?<?0.05).

Conclusion

In our study, the evaluation of serum Cu, Zn and Se trace element levels and plasma MDA levels according to GSTM1 gene variations genotype distributions were enabled to obtain important biomarkers in terms of CRC development and progression.

     

Does radiotherapy increase oxidative stress? A study with nasopharyngeal cancer patients revealing anomalies in isoprostanes measurements

Abstract

This study aimed to examine if exposure to ionizing radiation during clinical radiotherapy (RT) causes increased oxidative damage. Seven patients with nasopharyngeal cancer (NPC) who underwent RT took part in this controlled-trial study. Blood and urine samples were obtained for F₂-isoprostanes (F₂-IsoPs) measurement. Urinary F₂-IsoPs levels were elevated pre-treatment and remained high (but did not increase) during treatment, but decreased to the normal range after treatment. Plasma F₂-IsoPs decreased significantly after the start of treatment before rising midway through treatment. Levels decreased significantly to below baseline following treatment. However, the patients were observed to have substantially lower levels of plasma esterified arachidonic acid (AA) residues than controls. The data shows that NPC is associated with elevated F₂-isoprostanes in urine and in plasma after correction for decreased AA levels. RT did not increase these levels and, indeed, was associated with falls in F₂-IsoPs. The validity and usefulness of correction of plasma F₂-IsoPs for lowered AA levels is discussed.     

Separation of free amino acids in human plasma by capillary electrophoresis with laser induced fluorescence: potential for emergency diagnosis of inborn errors of metabolism

Free amino acids (AAs) in human plasma are derivatized with 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) and analyzed by capillary electrophoresis (CE) with laser induced fluorescence (LIF) detection. The labeling procedure is significantly improved over results reported previously. Derivatization can be completed in 40 min, with concentrations as low as 4×10⁻⁸ M successfully labeled in favourable cases. Twenty-nine AAs (including 2 internal standards) are identified and can be reproducibly separated in 70 min. Migration time RSD values for 23 of these AAs were calculated and found in the range from 0.5 to 4%. The rapid derivatization procedure and the resolution obtained in the separation are sufficient for a semi-quantitative, emergency diagnosis of several inborn errors of metabolism (IEM). Amino acid profiles for both normal donor plasma samples and plasma samples of patients suffering from phenylketonuria, tyrosinemia, maple syrup urinary disease, hyperornithinemia, and citrullinemia are studied.     

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients

Context: Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin.

Objective: To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians).

Materials and methods: One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established.

Results: There was interethnic variation of plasma AAG level; it was 182?±?85?mg/dl in Chinese, 237?±?94?mg/dl in Malays and 240?±?83?mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash.

Conclusions: This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.     

Plasma levels of pentraxin 3 in patients with spondyloarthritis

Context: Determining the disease’s inflammatory activity in spondyloarthritis (SpA) is difficult although very important as it is this that drives treatment.

Objective: To investigate if plasma pentraxin-3 (PTX3) could act as an inflammatory marker in SpA.

Methods: Eighty one SpA patients (11 with psoriatic arthritis (PsoA) and 70 with ankylosing spondylitis (AS)) and 90 gender and age paired controls were studied for plasma PTX3 levels by ELISA. Patients had determinations of disease activity through C reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP. Epidemiological, clinical and treatment data were collected through chart review.

Results: SpA patients had lower concentrations of plasma PTX3 than controls (median of 0.95?ng/mL vs 1.64?ng/mL; p?p?=?0.42). Uveitis, presence of HLA B27, tobacco exposure, age and disease duration did not influence PTX3 levels.

Conclusions: PTX3 plasma levels do not reflect disease activity in SpA. However, it probably participates in the ethiopathogenetic process, as it is consumed in these patients.     

LncRNA LINC00324 is upregulated in intervertebral disk degeneration and upregulates FasL in nucleus pulposus cells

Background

It has been reported that long intergenic non-protein-coding RNA 324 (LINC00324) promotes liver cancer by upregulating Fas ligand (FasL), which is a major player in intervertebral disk degeneration (IDD), indicating the involvement of LINC00324 in IDD. This study was carried out to investigate the interaction between LINC00324 and FasL in IDD.

Methods

Plasma samples were collected from both IDD (n?=?60) and healthy controls (n?=?60). The expression of LINC00324 and FasL in plasma was determined by RT-qPCR. The interactions between LINC00324 and FasL in nucleus pulposus (NP) cells were analyzed by overexpression experiments.

Results

LINC00324 and FasL were upregulated in IDD patients, and they were positively correlated. After treatment, the expression levels of FasL and LINC00324 were significantly decreased. In NP cells, overexpression of LINC00324 increased the expression of FasL at both mRNA and protein levels, while overexpression of FasL did not affect the expression of LINC00324.

Conclusion

LINC00324 may upregulate FasL in IDD to promote disease progression.

     

Distinct Genetic Alterations in Colorectal Cancer

Background

Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities.

Methodology/Principal Findings

We applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations.

Conclusions/Significance

Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.     

Altered redox status in the blood of psoriatic patients: involvement of NADPH oxidase and role of anti-TNF-α therapy

Abstract

Background

Psoriasis is a chronic hyperproliferative inflammatory skin disease, characterized by a generalized redox imbalance. Anti-tumor necrosis factor (TNF)-α therapy is widely used for the treatment of this disease, but its effect on blood redox status hasn't been explored.

Objective

To investigate the effects of anti-TNF-α therapy on blood redox status in psoriatic patients.

Methods

Twenty-nine psoriatic patients (PSO) were divided into two groups: one remained untreated (NRT) and to another the anti-TNF-α therapy was prescribed (TR). The levels of main oxidative stress markers and total antioxidant capacity (TAC) in plasma, levels of total reactive oxygen species (ROS) production, lipoperoxidation, TAC, glutathione content, and activity of NADPH oxidase in white blood cells (WBC) were evaluated in PSO, in NTR and TR after 6 months of the study.

Results

Plasma levels of malondialdehyde (MDA) and protein carbonyl content (PCO), ROS production, lipoperoxidation, and glutathione content in WBC were increased, while TAC in both plasma and WBC was decreased in PSO with respect to controls. In the plasma of TR, levels of MDA and PCO were significantly lower with respect to PSO and NTR. The activity of NADPH oxidase was significantly increased in WBC of PSO and NTR but not in TR versus controls.

Discussion

Our results represent novel data about the redox status of WBC in psoriatic patients. A significant redox-balancing effect of anti-TNF-α therapy, probably associated with the normalization of NADPH oxidase activity in WBC, was demonstrated.     

Association between Plasma 25-Hydroxyvitamin D,Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

Background

African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs).

Methods

Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3.

Results

AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (OR_T3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and OR_T3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null.

Conclusions

Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study.     

Adiponectin multimers and metabolic syndrome traits: relative adiponectin resistance in African Americans

African Americans (AAs) tend to have lower total adiponectin levels compared to European Americans (EA); however, it is not known whether race affects adiponectin multimer distribution and their relationships to metabolic traits. We measured total adiponectin, high molecular weight (HMW), low molecular weight (LMW) (i.e., hexamer), and trimer adiponectin in 132 normoglycemic premenopausal women (75 AAs, 57 EAs), together with measures of total and abdominal fat, plasma lipids, insulin sensitivity (S(i)), and genetic admixture estimates. We found that lower total adiponectin in AAs was explained by reduced LMW, and trimer forms because levels of HMW did not differ between races. In EAs, HMW was highly correlated with multiple metabolic syndrome traits. In contrast, the LMW and trimer forms were most highly correlated with metabolic traits in AAs, including abdominal adiposity, lipids, and S(i). At similar levels of visceral adiposity, AAs exhibited significantly lower LMW adiponectin than EAs. Similarly, at comparable levels of HMW and LMW adiponectin, AAs were more insulin resistant than their EA counterparts. In conclusion, (i) serum adiponectin is lower in AAs predominantly as a result of reduced concentrations of LMW and trimers multimeric forms; (ii) LMW and trimer, not HMW, are most broadly correlated with metabolic traits in AAs. Thus, HMW adiponectin may exert less bioactivity in explaining the metabolic syndrome trait cluster in populations of predominant African genetic background.     

Levels of plasma glycan-binding auto-IgG biomarkers improve the accuracy of prostate cancer diagnosis

Strategies to improve the early diagnosis of prostate cancer will provide opportunities for earlier intervention. The blood-based prostate-specific antigen (PSA) assay is widely used for prostate cancer diagnosis but specificity of the assay is not satisfactory. An algorithm based on serum levels of PSA combined with other serum biomarkers may significantly improve prostate cancer diagnosis. Plasma glycan-binding IgG/IgM studies suggested that glycan patterns differ between normal and tumor cells. We hypothesize that in prostate cancer glycoproteins or glycolipids are secreted from tumor tissues into the blood and induce auto-immunoglobulin (Ig) production. A 24-glycan microarray and a 5-glycan subarray were developed using plasma samples obtained from 35 prostate cancer patients and 54 healthy subjects to identify glycan-binding auto-IgGs. Neu5Acα2-8Neu5Acα2-8Neu5Acα (G81)-binding auto-IgG was higher in prostate cancer samples and, when levels of G81-binding auto-IgG and growth differentiation factor-15 (GDF-15 or NAG-1) were combined with levels of PSA, the prediction rate of prostate cancer increased from 78.2% to 86.2% than with PSA levels alone. The G81 glycan-binding auto-IgG fraction was isolated from plasma samples using G81 glycan-affinity chromatography and identified by N-terminal sequencing of the 50 kDa heavy chain variable region of the IgG. G81 glycan-binding 25 kDa fibroblast growth factor-1 (FGF1) fragment was also identified by N-terminal sequencing. Our results demonstrated that a multiplex diagnostic combining G81 glycan-binding auto-IgG, GDF-15/NAG-1 and PSA (≥?2.1 ng PSA/ml for cancer) increased the specificity of prostate cancer diagnosis by 8%. The multiplex assessment could improve the early diagnosis of prostate cancer thereby allowing the prompt delivery of prostate cancer treatment.

     

Changes in the levels of thioredoxin and indoleamine-2,3-dioxygenase activity in plasma of patients with colorectal cancer treated with chemotherapy

Increased oxidative stress and indoleamine-2,3-dioxygenase (IDO) activity have been reported in cancer, but their relationship with chemotherapy remains unknown. The aim of the present study was to examine wether the chemotherapy treatments used in colorectal cancer had an additional effect on oxidative stress and on IDO activity. Plasma samples were collected from 27 colorectal cancer patients on cytostatic treatment, 27 with cytostatic drugs plus monoclonal antibodies (cytostatic-Mabs) and 15 non-treated patients. All patients with colorectal cancer had high plasma malondialdehyde (MDA), thioredoxin (Trx) levels, and elevated IDO activity in plasma (IDOp) and in dendritic cells (IDOc). This study shows that treatment with cytostatics have an effect on oxidative stress by increasing MDA levels and by decreasing Trx levels and IDO activity. However, treatment with cytostatic-Mabs showed no effect on MDA levels but decreased Trx levels, and the IDO activity showed values similar to the healthy group. Significant correlations between plasma IDO activity and the levels of Trx (r = 0.2062, p < 0.05) and MDA (r = 0.2873, p < 0.005) were observed. Furthermore, our study suggests that IDO activity measured as kynurenine levels could be used as a marker of the response to the chemotherapy treatments, although further studies are necessary.     

Intakes of whey protein hydrolysate and whole whey proteins are discriminated by LC–MS metabolomics

Whey protein improves fasting lipids and insulin response in overweight and obese individuals. Whey hydrolysate was recently shown to be more active than whole protein but the differences in metabolite profiles after intake remain unknown. This study discriminates plasma profiles after intake of four different whey protein fractions and establishes new hypotheses for the observed effects. Obese, non-diabetic subjects were included in the randomized, blinded, cross-over meal study. Subjects ingested a high-fat meal containing whey isolate (WI), whey concentrate hydrolysate (WH), α-lactalbumin or caseinoglycomacropeptide as the protein source. Plasma samples were collected at five time points and metabolites analysed using LC–Q-TOF–MS. Plasma concentrations of ten amino acids (AAs) were different between the meals. The plasma levels of AAs and AA derivatives were generally directly related to the AA composition of the meals. Highly elevated plasma levels of a number of cyclic dipeptides and other AA metabolites were found following intake of the WH meal and these metabolites are primary candidates to explain the superior insulinotropic effect of WH. The manufacturing process of WH caused oxidization of methionine to methionine sulfoxide which in turn caused in vivo generation of N-phenylacetyl-methionine and N-phenylacetyl-methionine sulfoxide. These two compounds have not previously been described in biological systems.     

Plasma soluble urokinase plasminogen activator receptor (suPAR) levels in systemic lupus erythematosus

Objective: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation. We aimed to characterize plasma suPAR levels in SLE patients.

Methods: We measured plasma suPAR, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 89 SLE patients and 29 healthy controls.

Results: suPAR and ESR values were higher in SLE than in controls, while CRP levels were comparable. ROC analysis of suPAR levels indicated a cut-off value of 5.70?ng/mL to distinguish patients with high disease activity (SLEDAI >8).

Conclusion: suPAR might be an objective marker for identifying SLE patients with active disease.     

Plasma Amino Acid Profiling Identifies Specific Amino Acid Associations with Cardiovascular Function in Patients with Systolic Heart Failure

BackgroundThe heart has close interactions with other organs’ functions and concomitant systemic factors such as oxidative stress, nitric oxide (NO), inflammation, and nutrition in systolic heart failure (HF). Recently, plasma amino acid (AA) profiling as a systemic metabolic indicator has attracted considerable attention in predicting the future risk of human cardiometabolic diseases, but it has been scarcely studied in HF.MethodsThirty-eight stable but greater than New York Heart Association class II symptomatic patients with left ventricular (LV) ejection fraction <45% and 33 asymptomatic individuals with normal B-type natriuretic peptide (BNP) value were registered as the HF and control groups, respectively. We analyzed fasting plasma concentrations of 41 AAs using high-performance liquid chromatography, serum NO metabolite concentration, hydroperoxide and high-sensitivity C-reactive protein measurements, echocardiography, and flow-mediated dilatation.ResultsWe found that 17 AAs and two ratios significantly changed in the HF group compared with those in the control group (p < 0.05). In the HF group, subsequent univariate and stepwise multivariate analyses with clinical variables revealed that Fischer ratio and five specific AAs, ie, monoethanolamine, methionine, tyrosine, 1-methylhistidine, and histidine have significant correlation with BNP, LV ejection fraction, LV end-diastolic volume index, inferior vena cava diameter, the ratio of early diastolic velocity of the mitral inflow to mitral annulus, and BNP, respectively (p < 0.05). Interestingly, further exploratory factor analysis categorized these AAs into hepatic-related (monoethanolamine, tyrosine, and Fischer ratio) and skeletal muscle-related (histidine, methionine, and 1-methylhistidine) components. Some categorized AAs showed unique correlations with concomitant factors: monoethanolamine, tyrosine, and Fischer ratio with serum NO concentration; histidine with serum albumin; and 1-methylhistidine with flow-mediated dilatation (p < 0.05).ConclusionsPlasma AA profiling identified correlations of specific AAs with cardiac function and concomitant factors, highlighting the cardio-hepatic-skeletal muscle axis in patients with systolic HF.