Magnetic particle-based chemiluminescence immunoassay for serum human heart-type fatty acid binding protein measurement.

OBJECTIVES: Human heart-type fatty acid binding protein (HFABP) is a biomarker for diagnosis, risk assessment, and prognosis of acute myocardial infarction, and we aimed to establish an immunoassay for HFABP quantitation. METHODS: Human HFABP monoclonal antibodies (mAbs) were developed, evaluated by enzyme-linked immunosorbent assay, and a chemiluminescence enzyme immunoassay (CLEIA) generated. Analytical performance of the CLEIA was evaluated by measuring serum HFABP. RESULTS: The prokaryotically expressed rHFABP was purified and four anti-HFABP mAbs with superior detection performance were obtained after immunizing BALB/c mice. MAbs 2B8 and 6B3 were selected as respective capture and detection antibodies for HFABP measurement by CLEIA (detection range, 0.01-128 µg/L). Results using the CLEIA showed excellent correlation (r, 0.9622) and the correlation coefficient was 0.9809 (P < 0.05) by the Tukey test statistical analysis with those of latex-enhanced immunoturbidimetry in hospitals. CONCLUSION: Our mAbs and CLEIA for HFABP detection represent new diagnostic tools for measurement of human serum HFABP.

Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity.

Heart-type fatty-acid binding protein (FABP3) is an essential cytosolic lipid transport protein found in cardiomyocytes. FABP3 binds fatty acids (FAs) reversibly and with high affinity. Acylcarnitines (ACs) are an esterified form of FAs that play an important role in cellular energy metabolism. However, an increased concentration of ACs can exert detrimental effects on cardiac mitochondria and lead to severe cardiac damage. In the present study, we evaluated the ability of FABP3 to bind long-chain ACs (LCACs) and protect cells from their harmful effects. We characterized the novel binding mechanism between FABP3 and LCACs by a cytotoxicity assay, nuclear magnetic resonance, and isothermal titration calorimetry. Our data demonstrate that FABP3 is capable of binding both FAs and LCACs as well as decreasing the cytotoxicity of LCACs. Our findings reveal that LCACs and FAs compete for the binding site of FABP3. Thus, the protective mechanism of FABP3 is found to be concentration dependent.

The independent prediction study of the effect of heart-type fatty acid binding protein on the severity and long-term cardiac function in Covid-19 patients.

The study was conducted to assess the predictive ability of the heart-type fatty acid binding protein (HFABP) on the severity and long-term cardiac function of Covid-19 infected persons. In the case of negative HsTn-T, we determined whether HFABP was related to the severity of Covid-19 or it was the long-term impact of cardiac function. Chi-square test and t-test were used to evaluate whether HFABP level was an independent predictor of myocardial injury and whether it was related to the severity of Covid-19 and the long-term impact of cardiac function. Among the 20 patients in each of the two groups (mild and severe), 27.5% of all had elevated HFABP. Two were HFABP positive in the mild group, and nine were HFABP positive in the severe group, with a significant difference between the two groups (P=0.013). The mean serum level of HFABP in the mild group was 3.96 ±1.80, compared with 6.70±3.77 in the severe group, with a significant difference between the two groups (P=0.003). In addition, after two years of follow-up, there was a statistically significant difference in the changes of cardiac function between the HFABP-positive group and the HFABP-negative group (P=0.037). These data indicate that among HsTn-T-negative Covid-19 patients, HFABP is a more sensitive and independent predictor of myocardial damage, and it is useful for distinguishing mild and severe Covid-19. The level of HFABP has a significant effect on the long-term changes of heart function in Covid-19 patients.

Heart-Type Fatty Acid Binding Protein, Cardiovascular Outcomes, and Death: Findings From the German CKD Cohort Study.

RATIONALE & OBJECTIVE: Heart-type fatty acid binding protein (H-FABP) is a biomarker that has been shown to provide long-term prognostic information in patients with coronary artery disease independently of high-sensitivity troponin T (hs-TNT). We examined the independent associations of H-FABP with cardiovascular outcomes in patients with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,951 patients enrolled in the German Chronic Kidney Disease (GCKD) study with an estimated glomerular filtration rate of 30-60 mL/min/1.73 m2 or overt proteinuria (urinary albumin-creatinine ratio > 300 mg/g or equivalent). EXPOSURE: Serum levels of H-FABP and hs-TNT were measured at study entry. OUTCOME: Noncardiovascular (non-CV) death, CV death, combined major adverse CV events (MACE), and hospitalization for congestive heart failure (CHF). ANALYTICAL APPROACH: Hazard ratios (HRs) for associations of H-FABP and hs-TNT with outcomes were estimated using Cox regression analyses adjusted for established risk factors. RESULTS: During a maximum follow-up of 6.5 years, 579 non-CV deaths, 190 CV deaths, 522 MACE, and 381 CHF hospitalizations were observed. In Cox regression analyses adjusted for established risk factors, H-FABP was associated with all 4 outcomes, albeit with lower HRs than those found for hs-TNT. After further adjustment for hs-TNT levels, H-FABP was found to be associated with non-CV death (HR, 1.57 [95% CI, 1.14-2.18]) and MACE (HR, 1.40 [95% CI, 1.02-1.92]) but with neither CV death (HR, 1.64 [95% CI, 0.90-2.99]) nor CHF hospitalizations (HR, 1.02 [95% CI, 0.70-1.49]). LIMITATIONS: Single-point measurements of H-FABP and hs-TNT. Uncertain generalizability to non-European populations. CONCLUSIONS: In this large cohort of patients with CKD, H-FABP was associated with non-CV death and MACE, even after adjustment for hs-TNT. Whether measurement of H-FABP improves cardiovascular disease risk prediction in these patients warrants further studies.

Variability in Cardiac Biomarkers during Hemodialysis: A Prospective Cohort Study.

BACKGROUND: The effect of hemodialysis on cardiac biomarkers is unclear. We sought to evaluate the degree and causes of intradialytic variability of high sensitivity troponin I (hs-TnI), galectin-3 (gal-3), and heart-type fatty acid binding protein (hFABP). METHODS: hs-TnI, gal-3, and hFABP were prospectively measured pre-dialysis and post-dialysis for 1 week every month for 6 months in 178 prevalent adult hemodialysis patients at a single center in Hamilton, Canada. The degree of change from pre-dialysis to post-dialysis for each cardiac biomarker was estimated with multilevel linear regression models. RESULTS: The median change in the concentration of hs-TnI during hemodialysis was -1 ng/L (interquartile range [IQR] -1 to 2 ng/L) while gal-3 and hFABP changed by -36.3 ng/mL (IQR -27.7 to -46.8 ng/mL) and -19.41 ng/mL (IQR -13.61 to -26.87 ng/mL), respectively. The median (IQR) percentage intradialytic changes for hs-TnI, gal-3, and hFABP were 2.6% (-4.4% to 12.5%), -59.8% (-54.7% to -64.8%) and -35.3% (-28.4% to -42.1%), respectively. Ultrafiltration was associated with an increase in concentration of hs-TnI, gal-3, and hFABP (mean 0.99 ng/L, 1.05 ng/mL, and 1.9 ng/mL per L ultrafiltration, respectively, P < 0.001). Both gal-3 and hFABP concentrations decreased in association with the volume of blood processed (P < 0.001) and with hemodialysis treatment time (P = 0.02 and P = 0.04) while hs-TnI concentration decreased only in association with hemodialysis treatment time (P < 0.001). CONCLUSIONS: Ultrafiltration volume and hemodialysis treatment time influenced hs-TnI, gal-3, and hFABP concentrations during hemodialysis and should be considered when interpreting their measurement.

Assessing the Performance of a Novel Point-of-Care Qualitative Assay for Early Diagnosis of Acute Coronary Syndrome.

BACKGROUND: Early and accurate diagnosis of acute coronary syndrome (ACS) is essential for initiating lifesaving interventions. In this article, the diagnostic performance of a novel point-of-care rapid assay (SensAheart©) is analyzed. This assay qualitatively determines the presence of 2 cardiac biomarkers troponin I and heart-type fatty acid-binding protein that are present soon after onset of myocardial injury. METHODS: We conducted a prospective observational study of consecutive patients who presented to the emergency department with typical chest pain. Simultaneous high-sensitive cardiac troponin T (hs-cTnT) and SensAheart testing was performed upon hospital admission. Diagnostic accuracy was computed using SensAheart or hs-cTnT levels versus the final diagnosis defined as positive/negative. RESULTS: Of 225 patients analyzed, a final diagnosis of ACS was established in 138 patients, 87 individuals diagnosed with nonischemic chest pain. In the overall population, as compared to hs-cTnT, the sensitivity of the initial SensAheart assay was significantly higher (80.4 vs. 63.8%, p = 0.002) whereas specificity was lower (78.6 vs. 95.4%, p = 0.036). The overall diagnostic accuracy of SensAheart assay was similar to the hs-cTnT (82.7% compared to 76.0%, p = 0.08). CONCLUSIONS: Upon first medical contact, the novel point-of-care rapid SensAheart assay shows a diagnostic performance similar to hs-cTnT. The combination of 2 cardiac biomarkers in the same kit allows for very early detection of myocardial damage. The SensAheart assay is a reliable and practical tool for ruling-in the diagnosis of ACS.

Evaluation of Heart-type Fatty Acid-binding Protein in Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: Although electrocardiography and cardiac troponin play important roles in the diagnosis of acute coronary syndrome (ACS), there remain unmet clinical needs. Heart-type fatty acid-binding protein (H-FABP) has been identified as an early diagnostic marker of acute myocardial infarction (AMI). In this study, we examined the diagnostic and prognostic value of H-FABP in patients suspected with ACS. METHODS: We conducted an observational single-center cohort study, including 89 adults aged 30 years or older, who presented to the emergency room (ER) within 24 hours after the onset of chest pain and/or dyspnea. We performed laboratory analysis and point-of-care testing (POCT) for cardiac markers, including H-FABP, troponin I, and creatine kinase-myocardial band. We also evaluated the correlation between cardiac markers and left ventricular (LV) dysfunction and extent of coronary artery disease (CAD). RESULTS: In patients presented to ER within 4 hours after symptom onset (n = 49), the diagnostic accuracy of H-FABP for AMI, as quantified by the area under the receiver operating characteristic curve, was higher (0.738; 95% confidence interval [CI], 0.591-0.885) than other cardiac markers. In POCT, the diagnostic accuracy of H-FABP (56%; 95% CI, 45-67) was significantly higher than other cardiac markers. H-FABP was correlated with not extent of CAD but post-AMI LV dysfunction. CONCLUSION: H-FABP is a useful cardiac marker for the early diagnosis of AMI and prediction of myocardia injury. Difference in the circulatory release timeline of cardiac markers could explain its utility in early-stage of myocardial injury.

[New cardiac biomarkers for early detection of myocardial infarction in cardiac surgery]. / Neue kardiale Biomarker zur frühen Detektion des Myokardinfarktes in der Herzchirurgie.

In-hospital mortality after cardiac surgery ranges from 2% to 8%. Many patients suffer from major adverse cardiovascular events, e.g. myocardial infarction, which in the long term can result in severe limitations in routine activities. Troponin plays the central role in identifying myocardial infarction; however, interpretation after cardiac surgery is difficult due to ischemia reperfusion injury and direct surgical trauma. Thus, the distinction between procedure-related myocardial injury and additional myocardial injury due to a new event is difficult. The fourth universal definition of type 5 myocardial infarction uses the 10â€¯× upper limit of normal (ULN) as cut-off and notably > 90% of patients after on-pump procedures exceed this cut-off. Clinical consequences are mostly unclear. The dynamics of copeptin and heart-type fatty acid binding protein (H-FABP) concentrations start very early, i.e. several hours before troponin. The characteristics of copeptin and H­FABP might help to overcome the limitations of troponin. This short narrative review gives a concise overview on this topic. Moreover, a brief view of future perspectives in this field is given.

Skin Ultrastructure and the Changes of HIF-2α, H-FABP Expression in the Myocardium of Electric Shock Death Rats.

ABSTRACT: Objective To observe the skin ultrastructure change of electric shock death rats and to test the expression changes of hypoxia-inducible factor-2α （HIF-2α） and heart type-fatty acid-binding protein （H-FABP） of myocardial cells, in order to provide basis for forensic identification of electric shock death. Methods The electric shock model of rats was established. The 72 rats were randomly divided into control group, electric shock death group and postmortem electric shock group. Each group was divided into three subgroups, immediate （0 min）, 30 min and 60 min after death. The skin changes of rats were observed by HE staining, the changes of skin ultrastructure were observed by scanning electron microscopy, and the expression of HIF-2α and H-FABP in rats myocardium was tested by immunohistochemical staining. Results The skin in the electric shock death group and postmortem electric shock group had no significant difference through the naked eye or by HE staining. Under the scanning electron microscope, a large number of cellular debris, cells with unclear boundaries, withered cracks, circular or elliptical holes scattered on the cell surface and irregular edges were observed. A large number of spherical foreign body particles were observed. Compared with the control group, the expression of HIF-2α in all electric shock death subgroups increased, reaching the peak immediately after death. In the postmortem electric shock group, HIF-2α expression only increased immediately after death, but was lower than that of electric shock death group （P<0.05）. Compared with the control group, the expression of H-FABP in all subgroups of electric shock death group and postmortem electric shock group significantly decreased. The expression of H-FABP in all subgroups of electric shock death group was lower than that of the postmortem electric shock group （P<0.05）. Conclusion Electric shock can increase HIF-2α expression and decrease H-FABP expression in the myocardium, which may be of forensic significance for the determination of electric shock death and identification of antemortem and postmortem electric shock.

Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. METHODS: A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. RESULTS: During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p < 0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p < 0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076-3.214; p = 0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409-4.650; p = 0.002). The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p < 0.05). CONCLUSIONS: Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.

Evaluation of the cardioprotective effects of crystalloid del Nido cardioplegia solution via a rapid and accurate cardiac marker: heart-type fatty acid-binding protein

Background/aim: Our aim in this study was to compare the efficacy and safety of crystalloid del Nido solution and cold blood cardioplegia solution on clinical and laboratory parameters. Materials and methods: Sixty patients who underwent elective coronary bypass operation between July 2019 and January 2020 were included in our study. Patients were divided into 2 groups of 30 patients using del Nido solution (DNS) and cold blood cardioplegia solution (CBCS), which were given for cardiac arrest. Demographic data, preoperative, postoperative 0th h, 6th h and 4th day creatine kinase myocardial band (CK-MB) and troponin I values were compared with a specific cardiac enzyme heart-type fatty acid-binding protein (H-FABP). Results: We found that aortic cross clamp duration and cardiopulmonary bypass (CPB) time were shorter in patients using del Nido solution than cold blood cardioplegia solution (57.30 ± 23.57 min, 76.07 ± 27.18 min, P = 0.006) (95.07 ± 23.06 min, 114.13 ± 33.93, P = 0.014). Total cardioplegia solution volume was higher in the cold blood cardioplegia solution group (1426.67 ± 416.00 vs. 1200 ± 310.73 P = 0.02). Preoperative and postoperative levels of cardiac enzymes including CK-MB, troponin I and H-FABP were comparable in del Nido solution and cold blood cardioplegia solution groups. Conclusion: According to these results, when we compare both demographic data and CK-MB, troponin I and H-FABP levels, both cardioplegia solutions were comparable regarding safety and efficacy in terms of myocardial protection.

Heart-type fatty acid-binding protein (H-FABP), pentraxin-3 (PTX-3) and thrombomodulin in bovine traumatic pericarditis.

The aim of this study was to evaluate the biomarkers of cardiac damage such as heart-type fatty acid-binding protein (H-FABP), pentraxin-3 (PTX-3), and thrombomodulin (TM) for the detection and prognosis of bovine traumatic pericarditis (TP). Spontaneous TP was diagnosed on the basis of history, clinical signs, complete blood count, glutaraldehyde test, ultrasonography, and pericardiocentesis findings. H-FABP, PTX-3 and TM levels in serum were compared between 25 Holstein cows diagnosed with spontaneous TP and 10 healthy control cows using bovine-specific ELISA kits. Serum H-FABP in cattle with TP was significantly (P < 0.05) higher than in the control group and positively correlated with cardiac troponin-I (cTnI), creatine kinase myocardial band (CK-MB), PTX-3 and TM (r = 0.683, 0.342, 0.448 and 0.424, respectively; P < 0.05). The serum levels of PTX-3 (P < 0.05) and TM (P < 0.05) in cattle with TP were significantly higher than in the control group. Cardiac damage biomarkers H-FABP, PTX-3 and TM may be useful in the diagnosis of bovine TP.

Role of Gal-3 and H-FABP in the early diagnosis of acute coronary syndrome.

OBJECTIVES: We aimed to compare the plasma levels of biomarkers such as: serum Gal-3, H-FABP, cTnI, and CK-MB in patients, who were admitted to the emergency room with chest pain, and to determine whether these biomarkers have early diagnostic value of acute coronary syndrome (ACS). METHODS: The study was performed in 60 patients aged ≥ 18 years, who were admitted to emergency room. These patients were divided into 3 groups: patients with STEMI (group I, n = 20), patients with NSTEMI (group II, n = 20), and patients with USAP (group III, n = 20). Serum Gal-3, H-FABP, cTnI, and CK-MB levels were measured at admission, and at the 2nd and 4th hours. RESULTS: There were statistically significant differences between the groups in terms of Gal-3 levels at admission, and the 2nd and 4th hours (p = 0.007, p = 0.002, and p = 0.001, respectively). There were statistically significant differences between the groups in terms of H-FABP levels at admission, and the 2nd and 4th hours (p = 0.001, p = 0.003, and p = 0.003, respectively).There were statistically significant differences between the groups in terms of cTnI levels at admission, and the 2nd and 4th hours (p < 0.001, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: According to the results of the study, cTnI, H-FABP, and Gal-3 are useful parameters that can be used in the early diagnosis of ACS (Tab. 4, Ref. 36).

[Heart - type fatty acid binding protein in prognosis of ischemic stroke at the hospital stage].

Heart - type fatty acid binding protein (h-FABP), in addition to myocardium, is also contained in the brain cells. The blood concentration of h-FABP in cerebral ischemia can be a marker of ischemic stroke course. AIM: To investigate the importance of h-FABP in the prognosis of ischemic stroke (IS). MATERIALS AND METHODS: The study included 302 patients in the acute period of ischemic stroke. All patients were determined the concentration of h-FABP in the serum 1 day by enzyme immunoassay. SPSS and Microsoft Excel software were used for statistical data processing. RESULTS: The most frequent adverse events at the hospital stage were lethal outcome (LO), thrombotic complications and pneumonia. Statistically significant differences in the level of h-FABP between the groups of presence and absence of LO were revealed both by confidence intervals of Central values and by statistical criteria. The ROC analysis values of h-FABP in the presence of the LO confirmed its predictive value, area under the curve amounted to 0.776±0.061 (0.655-0.896), p.

Heart-type fatty acid binding protein (H-FABP) as a biomarker for acute myocardial injury and long-term post-ischemic prognosis.

Acute myocardial infarction (AMI) is a life-threatening event. Even with timely treatment, acute ischemic myocardial injury and ensuing ischemia reperfusion injury (IRI) can still be difficult issues to tackle. Apart from radiological and other auxiliary examinations, laboratory tests of applicable cardiac biomarkers are also necessary for early diagnosis and close monitoring of this disorder. Heart-type fatty acid binding protein (H-FABP), which mainly exists inside cardiomyocytes, has recently emerged as a potentially promising biomarker for myocardial injury. In this review we discuss the sensitivity and specificity of H-FABP in the assessment of myocardial injury and IRI, especially in the early stage, and its long-term prognostic value in comparison with other commonly used cardiac biomarkers, including myoglobin (Mb), cardiac troponin I (cTnI), creatine kinase MB (CK-MB), C-reactive protein (CRP), glycogen phosphorylase isoenzyme BB (GPBB), and high-sensitivity cardiac troponin T (hs-cTnT). The potential and value of combined application of H-FABP with other biomarkers are also discussed. Finally, the prospect of H-FABP is summarized; several technical issues are discussed to facilitate wider application of H-FABP in clinical practice.

Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies.

BACKGROUND: Although cardiac troponin is the cornerstone in diagnosis of acute myocardial infarction (AMI), the accuracy is still suboptimal in the early hours after chest pain onset. Due to its small size, heart-type fatty acid-binding protein (H-FABP) has been reported accurate in diagnosis of AMI, however, this remains undetermined. The aim is to investigate the diagnostic performance of H-FABP alone and in conjunction with high-sensitivity troponin (hs-Tn) within 6 hours of symptom onset. Furthermore, accuracy in 0h/3h algorithm was also assessed. METHODS: Medline and EMBASE databases were searched; sensitivity, specificity and area under ROC curve (AUC) were used as measures of the diagnostic accuracy. We pooled data on bivariate modelling, threshold effect and publication bias was applied for heterogeneity analysis. RESULTS: Twenty-two studies with 6602 populations were included, pooled sensitivity, specificity and AUC of H-FABP were 0.75 (0.68-0.81), 0.81 (0.75-0.86) and 0.85 (0.82-0.88) within 6 hours. Similar sensitivity (0.76, 0.69-0.82), specificity (0.80, 0.71-0.87) and AUC (0.85, 0.82-0.88) of H-FABP were observed in 4185 (63%) patients in 0h/3h algorithm. The additional use of H-FABP improved the sensitivity of hs-Tn alone but worsened its specificity (all p<0.001), and resulted in no improvement of AUC (p>0.99). There was no threshold effect (p=0.18) and publication bias (p=0.31) in this study. CONCLUSIONS: H-FABP has modest accuracy for early diagnosis of AMI within 3 and 6 hours of symptom onset. The incremental value of H-FABP seemed much smaller and was of uncertain clinical significance in addition to hs-Tn in patients with suspected AMI. Routine use of H-FABP in early presentation does not seem warranted.

Multifaceted analyses of the interactions between human heart type fatty acid binding protein and its specific aptamers.

BACKGROUND: Aptamer-protein interaction studies have been mainly confined to dissociation constant (Kd) determination. A combinatorial approach involving limited proteolysis mass spectroscopy, molecular docking and CD studies is reported here to elucidate the specific interactions involved. METHODS: To generate aptamers specific for human FABP3, SELEX was performed incorporating counter SELEX cycles against control FABPs and GST tag, followed by their characterization by EMSA, CD and SVD analysis. Based on computationally obtained aptamer-protein complex models, the interacting aptamer, and protein residues were predicted and supported by limited proteolysis experiments. RESULTS: Two aptamers N13 and N53 specific for human fatty acid binding protein (FABP3) were isolated with corresponding Kd of 0.0743±0.0142µM and 0.3337±0.1485µM for FABP3 interactions. Both aptamers possess stable B-DNA structures at salt concentration of 100mM and pH range (6-9). The N13 aptamer led interaction involved 3 salt bridges and 2 hydrogen bonds, whereas N53 had 2 salt bridges with 8 hydrogen and 7 hydrophobic interactions. CONCLUSIONS: The aptamers generated are the first to be reported against human FABP3. The higher interaction footprint of N53 incited synergistic conformational changes in both N53 and FABP3 during interaction, leading to a decline in binding affinity in comparison to N13 which corroborated to the calculated Kd values. GENERAL SIGNIFICANCE: This combinatorial method may be used to retrieve the possible specific binding modes and interaction patterns involved in large aptamer-protein complexes. Thus the method can be exploited to identify the optimum aptamer length for in-depth structure-function studies and its tailored applications.

Heart-Type Fatty Acid Binding Protein and High-Dose Methylprednisolone in Pediatric Cardiac Surgery.

OBJECTIVES: Corticosteroids possess cardioprotection in experimental cardiac ischemia/reperfusion. The authors hypothesized that if cardioprotection of corticosteroids occured during pediatric cardiac surgery, then methylprednisolone used in cardiopulmonary bypass prime would reduce postoperative concentrations of heart-type fatty-acid-binding protein, a cardiac biomarker. DESIGN: A double-blind, placebo-controlled, randomized clinical trial. SETTING: Operating room and pediatric intensive care unit of a university hospital. PARTICIPANTS: Forty-five infants and young children undergoing ventricular or atrioventricular septal defect correction. INTERVENTIONS: The patients received one of the following: 30 mg/kg of methylprednisolone intravenously after anesthesia induction (n = 15), 30 mg/kg of methylprednisolone in cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15). MEASUREMENTS AND MAIN RESULTS: Plasma heart-type fatty-acid-binding protein (hFABP) was measured. Preoperatively, hFABP did not differ among the study groups. Methylprednisolone administered preoperatively and in the cardiopulmonary bypass prime solution reduced hFABP by 44% (p = 0.010) and 38% (p = 0.033) 6 hours postoperatively. hFABP significantly correlated with concomitant troponin T after protamine administration (R = 0.811, p < 0.001) and 6 hours postoperatively (R = 0.806, p < 0.001). CONCLUSIONS: Methylprednisolone in cardiopulmonary bypass prime solution administered only a few minutes before cardiac ischemia confered cardioprotection of the same magnitude as preoperative methylprednisolone as indicated by hFABP concentrations. Rapid cardioprotective actions of corticosteroids in pediatric heart surgery observed previously experimentally may have occurred.

Different characteristics of cardiac biomarkers to decide and predict the culprit lesions in patients with suspicious acute coronary syndrome.

This multicenter prospective study was conducted to assess high-sensitivity troponin T (hs-TnT) and other biomarkers to decide and predict culprit lesions indicated for emergency percutaneous coronary intervention (PCI) in patients with suspicious acute coronary syndrome (ACS). We have reported Hs-TnT is the most sensitive biomarker for earlier diagnosis and decision making in patients with suspected ACS. In this study, we had conducted subanalysis investigating the usefulness for prediction of ACS culprit lesion. The patients with suspicious ACS and initially negative whole-blood rapid troponin T test, who underwent coronary angiogram (CAG), were enrolled (n = 74). Hs-TnT, quantitative assay for conventional troponin T (c-TnT), creatine kinase MB isozyme (CK-MB), and heart-type fatty acid-binding protein (H-FABP) were simultaneously measured. ACS culprit lesion was described as total occlusion, subtotal occlusion, and/or angiographical unstable lesion such as thrombosis, ulceration or irregularity. The CAG revealed that 49 cases had ACS lesions to be indicated for emergency PCI. The areas under the ROC curves and ROC-optimized cut-off of hs-TnT, c-TnT, CK-MB, and H-FABP were 0.75, 0.67, 0.68, and 0.75, respectively, and 18, 11, 2.0, and 4.6 ng/ml, respectively. In patients with total occlusion and 90-99 % of diameter stenosis (TIMI 2 or 3), hs-TnT could predict emergency PCI with significantly higher sensitivity compared with H-FABP (hs-TnT >14 ng/ml; 71 %, and H-FABP >6.2 ng/dl; 51 %, p = 0.021) and other biomarkers. Meanwhile, H-FABP displayed significant correlations with number of diseased vessels and presence of thrombotic lesion. The present study first revealed different characteristics of correlation between the angiographic culprit lesions and each cardiac biomarker. For prediction of ACS lesions requiring emergency PCI, hs-TnT had the highest sensitivity with satisfied analytical precision.

Heart-Type Fatty Acid-Binding Protein, in Early Detection of Acute Myocardial Infarction: Comparison with CK-MB, Troponin I and Myoglobin.

The study aimed to investigate whether heart-type fatty acid binding protein (H-FABP) measurement provides additional diagnostic value to that of conventional cardiac markers in acute myocardial infarction (AMI) within first 6 h after the onset of symptoms. The study included 120 subjects: 60 AMI cases and 60 age and sex matched controls. The cases and controls were further divided into 2 subgroups depending on the time since onset of chest pain as (1) subjects within 3 h and (2) between 3 and 6 h of onset of chest pain. In all the cases and controls, serum H-FABP concentration was measured by Immunoturbidimetric method, serum Troponin I and myoglobin concentrations by Chemiluminescence immunoassay and serum CK-MB concentration by Immuno-inhibition method. The sensitivity, specificity, positive and negative predictive values of H-FABP were significantly greater than CK-MB and myoglobin but were lesser than Troponin I in patients with suspected AMI in both within 3 h and 3-6 h groups. Receiver operating characteristic curves demonstrated greatest diagnostic ability for Troponin I (AUC = 0.99, p < 0.001) followed by H-FABP (AUC = 0.906, p < 0.001) within 3 h and 3-6 h after the onset of chest pain. In conclusion, the diagnostic value of H-FABP is greater than CK-MB and myoglobin but slightly lesser than troponin I for the early diagnosis of AMI within first 6 h of chest pain. H-FABP can be used as an additional diagnostic tool for the early diagnosis of AMI along with troponin I.