The cardiac biomarkers troponin I and CK-MB in nonpregnant and pregnant goats, goats with normal birth, goats with prolonged birth, and goats with pregnancy toxemia

This study was designed to establish the reference range for the cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase myocardial band (CK-MB) in nonpregnant and pregnant goats, goats with normal birth, goats with prolonged birth associated with dystocia, and goats with pregnancy toxemia. Fifty-seven does, categorized into three groups (G1 to G3), were used. These groups were comprised of 20 healthy does (G1), 19 does with prolonged birth (G2), and 18 does with pregnancy toxemia (G3). Six blood samples (T0 to T5) were collected from G1. The first blood sample (T0) was taken before insemination, the second (T1) at the first trimester, the third (T2) at the second trimester, the fourth (T3) at the last trimester, the fifth (T4) within 12 h of parturition, and the sixth blood sample (T5) was taken 10 days after parturition. A sample of blood was obtained from G2 and G3 upon admission to the hospital. At T0 to T3, no cTnI was detected in any of the 20 does in G1. At parturition (T4), seven of the 20 goats (35%) exhibited slightly elevated cTnI concentrations (range, 0.01 to 0.04 ng/mL). Ten days after parturition (T5), cTnI was not detected in any of the 20 goats. In 10 of the 19 goats (53%) with prolonged birth (G2), the cTnI was significantly elevated to a mean value of 0.094 ± 0.155 ng/mL, with a maximum value of 0.61 ng/mL. In 16 of the 18 goats (89%) with pregnancy toxemia (G3), the cTnI was significantly elevated to a value of 0.852 ± 1.472 ng/mL, with a maximum value of 5.219 ng/mL. Comparing the values of CK-MB in G1 (T0 to T5), G2 and G3 revealed nonsignificant differences. Only a slight elevation in the CK-MB levels in goats with prolonged birth (G2) was noted. We concluded that in healthy does, the cardiac biomarker cTnI is not elevated during normal pregnancy. The serum cTnI concentration may be elevated in a number of goats at normal vaginal or cesarean delivery. Finally, cTnI is significantly elevated in does with pregnancy toxemia and could be used as a prognostic indicator in such cases. The cardiac biomarker CK-MB is not a good indicator of parturition stress in does. Serum cTnI is elevated in goats with pregnancy toxemia, indicating some degree of cardiac dysfunction.     

The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes

Introduction

Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/β-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease.

Functional Effects of a Restrictive-Cardiomyopathy-Linked Cardiac Troponin I Mutation (R145W) in Transgenic Mice

The human cardiac troponin I (hcTnI) mutation R145W has been associated with restrictive cardiomyopathy. In this study, simultaneous measurements of ATPase activity and force in skinned papillary fibers from hcTnI R145W transgenic mice (Tg-R145W) were explored. Tg-R145W fibers showed an ∼ 13-16% increase in maximal Ca²⁺-activated force and ATPase activity compared to hcTnI wild-type transgenic mice. The force-generating cross-bridge turnover rate (g) and the energy cost (ATPase/force) were the same in all groups of fibers. Also, the Tg-R145W fibers showed a large increase in the Ca²⁺ sensitivity of both force development and ATPase. In intact fibers, the mutation caused prolonged force and intracellular [Ca²⁺] transients and increased time to peak force. Analysis of force and Ca²⁺ transients showed that there was a 40% increase in peak force in Tg-R145W muscles, which was likely due to the increased Ca²⁺ transient duration. The above cited results suggest that: (1) there would be an increase in resistance to ventricular filling during diastole resulting from the prolonged force and Ca²⁺ transients that would result in a decrease in ventricular filling (diastolic dysfunction); and (2) there would be a large (approximately 53%) increase in force during systole, which may help to partly compensate for diastolic dysfunction. These functional results help to explain the mechanisms by which these mutations give rise to a restrictive phenotype.     

Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility of human cardiac α-tropomyosin

α-Tropomyosin (αTm) is central to Ca²⁺-regulation of cardiac muscle contraction. The familial hypertrophic cardiomyopathy mutation αTm E180G enhances Ca²⁺-sensitivity in functional assays. To investigate the molecular basis, we imaged single molecules of human cardiac αTm E180G by direct probe atomic force microscopy. Analyses of tangent angles along molecular contours yielded persistence length corresponding to ∼35% increase in flexibility compared to wild-type. Increased flexibility of the mutant was confirmed by fitting end-to-end length distributions to the worm-like chain model. This marked increase in flexibility can significantly impact systolic and possibly diastolic phases of cardiac contraction, ultimately leading to hypertrophy.     

脓毒症小鼠心肌损伤与中性粒细胞浸润的关系

目的:探讨脓毒症小鼠心肌损伤与中性粒细胞浸润的关系。方法:复制脓毒症动物模型,分对照组、假手术组、造模组,并设不同的时间点(2h、4h、8h、12h)。采用双抗夹心酶联免疫法(ELISA)检测血清肌钙蛋白(IcTnI),并测心肌组织髓过氧化物酶(MPO)活性。结果:正常组与假手术组各时间点血清cTnI、心肌组织MPO活性均无显著性差异。造模组心肌组织MPO活性较正常组和假手术组均有明显升高(P<0.05),且随着时间进展而增加;造模组血清cTnI浓度随着时间进展而增加,2小时与正常组及假手术组无显著性差异(P>0.05),4小时后显著高于正常组和假手术组(P<0.05);血清cTnI浓度与心肌组织MPO活性呈显著正相关(r=0.700,P=0.000)。结论:脓毒症心肌损伤时,心肌组织存在中性粒细胞浸润,中性粒细胞浸润程度与心肌损伤显著正相关。     

血浆periostin蛋白、cTnI及BNP与扩张性心肌病患者室壁应力的相关性研究

摘要 目的：探讨血浆periostin蛋白、肌钙蛋白（troponin I,cTnI）、脑钠肽（brain natriureticpe ptide,BNP）与扩张性心肌病患者室壁应力（mean wall stress,MWS）的相关性及其对扩张性心肌病预后评估价值。方法：选择2019年3月~2022年3月期间我院收治89例扩张性心肌病患者和同期体检79例健康者作为研究组及对照组,均检测血浆periostin蛋白、cTnI、BNP水平以及MWS变化。随访患者出院一年心血管不良事件发生情况,进行相关统计学分析,并探讨其临床价值。结果：研究组血浆periostin蛋白、cTnI、BNP以及MWS水平均显著高于对照组（P＜0.05）;Pearson相关性分析显示,血浆periostin蛋白、cTnI、BNP水平与MWS均为正相关（r=0.619,0.428,0.665;P＜0.05）;预后良好患者血浆periostin蛋白、cTnI、BNP以及MWS水平均显著低于预后不良患者（P＜0.05）;ROC曲线显示,分别用血浆periostin蛋白、cTnI、BNP、MWS评估患者预后AUC相应值为0.973、0.702、0.803、0.802,血浆periostin蛋白、cTnI、BNP分别联合MWS评估患者预后相应的AUC值为0.984、0.810、0.857。结论：扩张性心肌病患者血浆periostin蛋白、cTnI及BNP水平与MWS及疾病预后相关,血浆periostin蛋白、cTnI及BNP分别联合MWS对疾病预后具有一定评估价值。     

Modulation of cardiac troponin C function by the cardiac-specific N-terminus of troponin I: influence of PKA phosphorylation and involvement in cardiomyopathies

The cardiac-specific N-terminus of cardiac troponin I (cTnI) is known to modulate the activity of troponin upon phosphorylation with protein kinase A (PKA) by decreasing its Ca²⁺ affinity and increasing the relaxation rate of the thin filament. The molecular details of this modulation have not been elaborated to date. We have established that the N-terminus and the switch region of cTnI bind to cNTnC [the N-domain of cardiac troponin C (cTnC)] simultaneously and that the PKA signal is transferred via the cTnI N-terminus modulating the cNTnC affinity toward cTnI_147-163 but not toward Ca²⁺. The K_d of cNTnC for cTnI_147-163 was found to be 600 μM in the presence of cTnI_1-29 and 370 μM in the presence of cTn1_1-29PP, which can explain the difference in muscle relaxation rates upon the phosphorylation with PKA in experiments with cardiac fibers. In the light of newly found mutations in cNTnC that are associated with cardiomyopathies, the important role played by the cTnI N-terminus in the development of heart disorders emerges. The mutants studied, L29Q (the N-domain of cTnC containing mutation L29Q) and E59D/D75Y (the N-domain of cTnC containing mutation E59D/D75Y), demonstrated unchanged Ca²⁺ affinity per se and in complex with the cTnI N-terminus (cTnI_1-29 and cTnI_1-29PP). The affinity of L29Q and E59D/D75Y toward cTnI_147-163 was significantly perturbed, both alone and in complex with cTnI_1-29 and cTnI_1-29PP, which is likely to be responsible for the development of malfunctions.     

病毒性心肌炎患者血清CK-MB、hs-CRP、IL-35 及cTnI水平的表达

目的:研究血清肌酸激酶同工酶(CK-MB)、超敏C-反应蛋白(hs-CRP)、白介素-35(IL-35)和肌钙蛋白(cTnI)对病毒性心肌炎的诊断意义。方法:研究对象为我院2012年1月至2015年1月间接受诊治的病毒性心肌炎病人63例,作为实验组,选取我院同时期健康体检人60例为对照组。对照两组血清CK-MB、hs-CRP、IL-35及cTnI的检测水平。结果:实验组CK-MB、hs-CRP及cTnI阳性率均明显高于对照组差异有统计学意义(P0.05);实验组的血清CK-MB、hs-CRP、IL-35及cTnI的检测结果:均明显高于对照组差异有统计学意义(P0.05);cTnI敏感度及特异度均是最高的,hs-CRP特异度高于CK-MB,但敏感度较低。结论:病毒性心肌炎患者血清CK-MB、hs-CRP、IL-35及cTnI可作为诊断的重要指标。