血清PⅢP检测在肝纤维化诊断中的临床应用

肝细胞外基质由胶原、氨基葡萄糖多糖和糖蛋白三类大分子物质构成，以胶原含量最多。目前公认肝脏至少有五种胶原，以I、Ⅲ、Ⅳ型为主，Ⅲ型前胶原是Ⅲ型胶原的生物合成前体，在成纤维细胞中合成并释放，这种前肽在细胞外被裂解转变为胶原，N端前肽Col 1—3在这一过程中以等分子比例形成Ⅱ型胶原，并进入循环。因而，血清N端前肽水平能用于测量Ⅲ型胶原的合成。     

血清PⅢP检测在肝纤维化诊断中的临床应用

一、组织学基础肝细胞外基质由胶原、氨基葡萄糖多糖和糖蛋白三类大分子物质构成,以胶原含量最多。目前公认肝脏至少有五种胶原,以Ⅰ、Ⅲ、Ⅳ型为主,Ⅲ型前胶原是Ⅲ型胶原的生物合成前体,在成纤维细胞中合成并释放,这种前肽在细胞外被裂解转变为胶原,N 端前肽 Col 1—3在这     

心肌细胞外基质研究进展

心肌细胞外基质(extracellular matrix，ECM)在维持心脏正常的结构和功能及细胞生长分化过程中起非常重要的作用。ECM由胶原、弹性蛋白、纤粘蛋白、层粘蛋白及蛋白聚糖等组成，其中最主要的成分是胶原。胶原是由心肌成纤维细胞(FBC)产生和分泌的，正常情况下处于合成与分解代谢的动态平衡之中。初始的心肌损伤激活体内多种神经内分泌激素及细胞因子，破坏了ECM合成与降解的动态平衡，导致ECM重构的发生。     

经皮冠状动脉介入治疗对急性心肌梗死患者胶原Ⅰ、Ⅲ和Fibulin-5的影响

目的:观察经皮冠状动脉介入治疗(PCI)对心肌细胞外基质重构的影响。方法:选择急性ST段抬高型前壁心肌梗死患者47例,按照是否行急诊PCI分为急诊PCI组(n=32)和非PCI组(n=15),并设置同期稳定性冠状动脉粥样硬化性心脏病患者30例为对照组。比较3组患者入院即刻,PCI术后1、7、30、45d血清胶原Ⅰ型C端胶原前肽(PⅠCP)、Ⅲ型N端胶原前肽(PⅢNP)及Fibulin-5水平。结果:不同处理方法对患者心肌细胞外基质重构有显著影响。对照组血清中PⅠCP、PⅢNP及Fibulin-5水平无显著变化;急诊PCI组及非PCI组PⅠCP、PⅢNP及Fibulin-5水平升高,7d后达到峰值,但急诊PCI组上述指标较非PCI组在同一时间窗明显降低(P均0.05)。结论:急诊PCI可减轻患者心肌细胞外基质重构,改善心脏功能。     

心肌纤维化相关信号通路的研究进展

正心肌纤维化(myocardial fibrosis,MF)是指心肌组织结构中胶原纤维的过度沉积,主要表现为细胞外基质(extracellular matrix,ECM)的合成和降解失衡,各类型胶原比例失衡,排列紊乱。MF特征是ECM的分泌增加及心肌细胞之间ECM的过量沉积。心肌中ECM由5种胶原蛋白组成,其中Ⅰ型和Ⅲ型胶原蛋白所占比例最高。MF在心室重构的过程中会导致心肌功能、代谢及传导异常,发展成为心     

细胞外基质的代谢

0 引言 细胞外基质(extracellular matrix,ECM)是指位于机体细胞外的非细胞性的有形或无定形成分,ECM的代谢包括ECM的合成与降解,ECM合成与降解失衡是肝纤维化形成的基础。 1 ECM合成 1.1 HSC的活化增殖 ECM的细胞来源是肝星状细胞(HSC)、肝细胞、内皮细胞及枯否细胞。其中HSC是ECM的主要细胞来源,因此HSC的活化是ECM合成的关键,静止的HSC靠近正常基底膜,含大量视黄酯,产生少量Ⅲ型胶原。肝损     

原发性高血压患者血清Ⅲ型前胶原氨基端肽的检测价值

心肌间质胶原主要为I、Ⅲ型胶原[1]。成纤维细胞生成的Ⅲ型前胶原分泌入细胞外间隙后会被特异性的肽酶分解,释出一个氨基末端肽(PⅢNP)。因而PⅢNP可作为Ⅲ型胶原合成的指标[1,2]。本文观察原发性高血压(EH)患者血清PⅢNP浓度,同时测血管紧张素Ⅱ(AngⅡ)含量,并与舒张功能作相关比较,以探讨PⅢNP作为心脏纤维化血清指标的临床价值。     

缺氧时心房钠尿肽分泌及其机制的研究进展

1981年De Bold等〔1〕在心脏的心房肌细胞中首次发现"排钠利尿素",并将其命名为心钠素(ANF)。后来,经研究发现,ANF是由肽类物质构成,因此最终命名为心房钠尿肽(ANP)。ANP是钠尿肽家族(NPs)的第一个成员,之后相继发现NPs的其他五大成员,即脑性利尿钠肽(BNP)、C-型利尿钠肽(CNP)、树眼镜蛇性利尿钠肽(DNP)、室性利尿钠肽(VNP)和珊瑚毒蛇性利尿钠肽(MNP)。所有NPs成员的共同结构特征是17个氨基酸组成一个环状结构,其中有11个氨基酸以二硫键相连,N端和C端氨基酸序列则随NPs成员及动物种类的不同而异。     

B型钠尿肽检测的临床意义

B型钠悄肽(BNP),又称脑钠素或脑钠肽,是钠尿肽(NP)家族中的一种。钠尿肽家族是一类通过一系列影响血管、肾和内分泌作用来帮助机体维持正常血压和细胞外流动液体量,具有调节血压和血容量等多方面作用的神经激素。目前,已知道的钠尿肽有四种：心房钠尿肽(又称A型钠尿肽,ANP)、B型钠尿肽(BNP)、C型钠尿肽(CNP)和D型钠尿肽(DNP)。四种NP都含有一个相同的由17个氨基酸组成的环状结构。除CNP是由血管内皮细胞合成分泌的外,A、B钠尿肽主要由心脏合成释放。     

肝纤维化四项血清标志物是否存在可信诊断价值

肝纤维化时当胶原的合成与沉积大于降解和吸收,导致细胞外基质(ECM)失衡,在肝脏中过多积聚和沉积,肝内胶原纤维增加进而逐渐形成肝纤维化,尤其是后期的降解减少是肝纤维化形成的主要机制[1].肝纤维化四项包括:(1)Ⅲ型前胶原( PCⅢ)及Ⅲ型前胶原氨基端肽(PⅢP,PⅢNP);(2)Ⅳ型胶原(CIV);(3)层粘连蛋白(LN);(4)透明质酸(HA).     

Metabolic therapy for the diabetic patients with ischaemic heart disease

Diabetic patients with ischaemic heart disease have a greater amount of myocardial ischaemia, often silent, and an increased incidence of heart failure compared to nondiabetic patients. This is the result of altered myocardial metabolism and accelerated atherogenesis with involvement of peripheral coronary segments causing chronic hypoperfusion and diffuse hybernation. In patients with diabetes mellitus and myocardial ischaemia, the metabolic changes occurring as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the diabetic metabolic changes. An important metabolic alteration of diabetes is the increase in free fatty acid concentrations and increased muscular and myocardial free fatty acid uptake and oxidation. This increased uptake and utilization of free fatty acid during stress and ischaemia is responsible for the increased susceptibility of the diabetic heart to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared to nondiabetic hearts. Given the metabolic alterations of the diabetic heart at rest and during episodes of myocardial ischaemia, a therapeutic approach aimed at an improvement of cardiac metabolism through manipulations of the utilization of metabolic substrates should result in an improvement of myocardial ischaemia and of left ventricular function. Modulation of myocardial free fatty acid metabolism should be the key target for metabolic interventions in patients with coronary artery disease with and without diabetes. In diabetic patients, the effects of modulation of free fatty acid metabolism should be even greater than those observed in patients without diabetes. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, decreases cardiac ischaemia and therefore prevents the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischaemia. Because of its effect on cardiac metabolism at rest, its effects on myocardial ischaemia and left ventricular function trimetazidine should always be considered for the treatment of diabetic patients with ischaemic heart disease with or without left ventricular dysfunction.     

Cardiac failure in coronary heart disease

Cardiac failure, which used to be rare in coronary heart disease, is now its most common complication. Coronary heart disease can cause or appear as cardiac failure through one or more of 12 mechanisms: acute myocardial infarction, acute reversible ischemia, right ventricular dysfunction, cardiogenic shock, acute mitral regurgitation, ventricular septal perforation, cardiac free wall rupture, ischemic cardiomyopathy, ventricular aneurysm, coexisting diseases, iatrogenesis, and pseudoheart failure. An understanding of the responsible mechanism or mechanisms is essential not only for appropriate treatment but also for prognostication. Various therapeutic modalities, both medical and surgical, should be able to improve not only symptoms but also survival. Current efforts in the management of patients with cardiac failure as a result of coronary heart disease should be aimed at prevention, both primary and secondary.     

Heart, aging, and hypertension.

Hypertension and aging adversely affect cardiovascular system and the heart is invariably involved. Manifestations of hypertensive heart disease and of the aging heart appear similar; ventricular hypertrophy, myocardial fibrosis, and impairments in ventricular function and coronary hemodynamics characterize both conditions. However, a great deal of evidence suggests that different underlying pathophysiological mechanisms may be involved. This report discusses most recent clinical and experimental findings and focuses on the alterations in nonmyocytic elements that are a part of heart involvement. Particular attention was given to factors that are responsible for exaggerated myocardial deposition of collagen that, by itself, may be responsible for ventricular dysfunction and impaired coronary hemodynamics in hypertensive and aging hearts. Newly developed therapeutical strategies, based on the most recent experimental and clinical studies, are also discussed.     

Cardiac involvement in Duchenne and Becker muscular dystrophy

Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation, not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction, heart block or malignant arrhythmias. Not only DMD/BMD patients, but also female carriers may present cardiac involvement. Clinically overt heart failure in dystrophinopathies may be delayed or absent, due to relative physical inactivity. The commonest electrocardiographic findings include conduction defects, arrhythmias (supraventricular or ventricular), hypertrophy and evidence of myocardial necrosis. Echocardiography can assess a marked variability of left ventricular dysfunction, independently of age of onset or mutation groups. Cardiovascular magnetic resonance (CMR) has documented a pattern of epicardial fibrosis in both dystrophinopathies’ patients and carriers that can be observed even if overt muscular disease is absent. Recently, new CMR techniques, such as postcontrast myocardial T1 mapping, have been used in Duchenne muscular dystrophy to detect diffuse myocardial fibrosis. A combined approach using clinical assessment and CMR evaluation may motivate early cardioprotective treatment in both patients and asymptomatic carriers and delay the development of serious cardiac complications.     

Diastolic function in valvular heart disease.

Diastolic dysfunction in patients with valvular heart disease is characterized by an impaired isovolumic relaxation, a normal or even enhanced early diastolic filling rate and an increased myocardial stiffness. These abnormalities do not depend on coexisting systolic dysfunction but are often combined. Several mechanisms are responsible for the occurrence of diastolic dysfunction, such as increased wall stress, altered myocardial structure, subendocardial hypoperfusion and/or diastolic calcium overload. Postoperative regression of myocardial hypertrophy is beneficial in regard to wall stress, subendocardial hypoperfusion and calcium overload but diastolic dysfunction might become worse after valve replacement due to a relative increase in interstitial fibrosis consequent to the decrease in myocyte mass (= myocardial remodeling). Persisting diastolic dysfunction with a substantial rise in left ventricular filling pressure can be observed during dynamic exercise in postoperative patients with preoperative severe pressure overload hypertrophy. Thus, diastolic dysfunction can be present as a primary derangement of cardiac function and can be unmasked as an abnormal response of diastolic filling pressure during exercise.     

Assessment of myocardial perfusion and fatty acid metabolism in a patient with Churg-Strauss syndrome associated with eosinophilic heart disease.

Churg-Strauss syndrome is characterized by asthma, eosinophilia and systemic necrotizing vasculitis; cardiac involvement (ie, eosinophilic heart disease) is the major cause of morbidity and mortality, although there are no reports of an association between left ventricular dysfunction because of eosinophilic heart disease and myocardial blood flow or myocardial fatty acid metabolism. A patient presented with Churg-Strauss syndrome associated with eosinophilic heart disease that had progressed to dilated cardiomyopathy. Coronary angiography, thallium-201 ((201)Tl) and iodine-123 beta-methyl-iodophenyl pentadecanoic acid ((123)I BMIPP) myocardial single photon emission computed tomography (SPECT) were performed to evaluate left ventricular dysfunction. Although coronary angiography was normal and (201)Tl SPECT showed no apparent image defect, (123)I BMIPP SPECT showed diffuse decreased accumulation, excepting the apex. The left ventricular dysfunction in patients with eosinophilic heart disease is associated with impaired myocardial fatty acid metabolism rather than with impaired myocardial blood flow.     

REVIEW: Sodium Channel (Dys)Function and Cardiac Arrhythmias

Cardiac voltage‐gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation and propagation of action potentials throughout the myocardium and consequently plays a central role in excitability of myocardial cells and proper conduction of the electrical impulse within the heart. The importance of sodium channels for normal cardiac electrical activity is emphasized by the occurrence of potentially lethal arrhythmias in the setting of inherited and acquired sodium channel disease. During common pathological conditions such as myocardial ischemia and heart failure, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. In addition, sodium channel dysfunction caused by mutations in the SCN5A gene, encoding the major sodium channel in heart, is associated with a number of arrhythmia syndromes. Here, we provide an overview of the structure and function of the cardiac sodium channel, the clinical and biophysical characteristics of inherited and acquired sodium channel dysfunction, and the (limited) therapeutic options for the treatment of cardiac sodium channel disease.     

Modern nuclear cardiac imaging in diagnosis and clinical management of patients with left ventricular dysfunction

Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.     

Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications

The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial. This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications. The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes. The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity). This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease.     

Systems Biology and Biomechanical Model of Heart Failure

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.