Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on acute and chronic heart failure (AHF/CHF) induced by ligation of the left anterior descending coronary artery for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+HSYA (100 mg kg(-1) by gavage) and CAL+diltiazem (20 mg kg(-1) by gavage). In the AHF model, heart function, as determined by haemodynamic studies and echocardiography, was improved significantly by pretreatment with HSYA or diltiazem. Significant reductions in elevated serum creatine phosphokinase, lactate dehydrogenase, malondialdehyde (MDA), glutamic oxalacetic transaminase, glutamic pyruvic transaminase and blood viscosity were observed, and the activity of serum superoxide dismutase (SOD) was enhanced (all P<0.01). In the CHF model, HSYA and diltiazem restored abnormal heart function, and completely suppressed the elevated plasma atrial natriuretic polypeptide (ANP) and endothelin-1 (ET-1), serum and left-ventricular tissue inducible nitric oxide (NO) synthase (iNOS), NO and MDA, and improved the decrease in SOD. HSYA and diltiazem improved cardiac performance in AHF and reduced cardiac remodelling in CHF by reducing tissue weight indices: left ventricular weight/body weight (BW), right ventricular weight/BW, kidney weight/BW and lung weight/BW, and attenuating increases in infarct size, inner diameter of the left ventricle and collagen volume fraction in non-infarcted areas, and the decrease in mean wall thickness of infarcted myocardium. These results suggest that HSYA exerted beneficial actions in cardiac performance in models of both AHF and CHF, mainly by suppressing ET-1, iNOS and oxidative stress in infarcted tissue.
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PMID:Protective effects of hydroxysafflor yellow A on acute and chronic congestive cardiac failure mediated by reducing ET-1, NOS and oxidative stress in rats. 1940 9

The failing heart produces a variety of biologically active humoral factors such as catecholamines, vasopressin, angiotensin II, aldosterone, atrial natriuretic polypeptide (ANP), brain natriuretic polypeptide (BNP), cytokines and so on, in order to recover the cardiac function through the mechano- and chemo-receptors in vivo. In particular, it has recently shown that the central nervous system plays a pivotal role in the progression of cardiac remodeling and the heart failure. Thereby, endogenous digitalis-like factor, angiotensisn II, aldostereone, and inflammatory cytokines in the brain are acting as the mediators. In fact, mineralocorticoid receptor blockers, such as spironolactone and eplerenone, are clinically useful to treat cardiac failure. However, these biomarkers are not available as laboratory tests because they are under investigation clinically. On the other hand, failing heart by itself produces natriuretic hormones such as ANP and BNP to rescue it. They dilate resistant vessels to reduce the afterload of the heart with the lowest concentrations. Then, natriuresis is caused with the increased concentrations to reduce the pre-load to the heart. The natriuresis is brought partially by reducing concentrations of plasma aldosterone. Therefore, concentrations of these natriuretic hormones are excellent biomarkers for the cardiac function. They increase in a variety of disease states like hypertension, acute/old myocardial infarction, angina pectoris, arrhythmias, cardiac failure, cardiomyopathy, renal failure and myocarditis. In particular, they are remarkably increased in patients with heart failure. Recently, a new biomarker, N-terminal pro-BNP (NT-proBNP) is registered as a clinically available laboratory test, which may be superior to BNP at the laboratory stand of view. It is because NT proBNP is not degraded in the circulation, stable even in serum and the higher concentration as compared to BNP.
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PMID:[Pathophysiology of heart failure and the biomarkers; brain natriuretic hormone as the class-1 recommendation by the new Japanese Guideline for Heart Failure]. 1828 62

Diabetic cardiomyopathy, structurally characterized by cardiomyocyte hypertrophy and increased extracellular matrix (ECM) protein deposition, eventually leads to heart failure. We investigated the role of transcriptional coactivator p300 and its interaction with myocyte enhancer factor 2 (MEF2) in diabetes-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed to variable levels of glucose. Cardiomyocytes were analyzed with respect to their size. mRNA expression of p300, MEF2A, MEF2C, atrial natriuretic polypeptide (ANP), brain natriuretic polypeptide (BNP), angiotensinogen (ANG), cAMP-responsive element binding protein-binding protein (CBP), and protein analysis of MEF2 were done with or without p300 blockade. We investigated the hearts of STZ-induced diabetic rats and compared them with age- and sex-matched controls after 1 and 4 mo of followup with or without treatment with p300 blocker curcumin. The results were that cardiomyocytes, exposed to 25 mM glucose for 48 h, showed cellular hypertrophy and augmented mRNA expression of ANP, BNP, and ANG, molecular markers of cardiac hypertrophy. Glucose caused a duration-dependent increase of mRNA and protein expression in MEF2A and MEF2C and transcriptional coactivator p300. Curcumin, a p300 blocker, and p300 siRNA prevented these abnormalities. Similarly, ANP, BNP, and ANG mRNA expression was significantly higher in the hearts of diabetic rats compared with the controls, in association with increased p300, MEF2A, and MEF2C expression. Treatment with p300 blocker curcumin prevented diabetes-induced upregulation of these transcripts. We concluded that data from these studies demonstrate a novel glucose-induced epigenetic mechanism regulating gene expression and cardiomyocyte hypertrophy in diabetes.
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PMID:Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level. 1841 74

Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presenting to an emergency department (ED) and is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes in direct proportion to wall tension, which lowers renin-angiotensin-aldosterone activation. For the diagnosis of CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in an elderly population, and in patients with renal dysfunction. They might also have a prognostic value. Studies have demonstrated that the use of BNP or NT-proBNP in dyspneic patients early following admission to the ED, reduced the time to discharge and total treatment cost. BNP and NT-proBNP should be available in every ED 24 h a day, because the literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients. The purpose of this review is to indicate recent developments in biomarkers of heart failure and to evaluate their impact on clinical use in the emergency setting.
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PMID:Differential diagnosis of acute dyspnea: the value of B natriuretic peptides in the emergency department. 1866 34

In previous studies, we have found that IGF-II and IGF-II receptor (IGF-IIR) dose dependently correlated with the progression of pathological hypertrophy after complete abdominal aorta ligation, which may play a critical role in angiotensin II-induced cardiomyocyte apoptosis. However, the detail mechanisms of IGF-IIR in the regulation of cell apoptosis in response to IGF-II remain unclear. By using IGF-IR short hairpin RNA to inhibit IGF-IR expression and using Leu27 IGF-II analog to activate specifically the IGF-IIR, we investigated the role of IGF-II/IGF-IIR activation and its downstream signaling. Our results revealed that IGF-II synergistically increased the cell apoptosis induced by suppressing of IGF-IR in neonatal rat ventricular myocytes. After binding of Leu27IGF-II, IGF-IIR became associated with alpha-q polypeptide, acted like a protein-coupled receptor to activate calcineurin, led to the translocation of Bad into mitochondria and release of cytochrome c into cytoplasm, and contributed to mitochondrial-dependent apoptosis in neonatal rat ventricular myocytes. Furthermore, inhibition of IGF-IIR, alpha-q polypeptide, or calcineurin by RNA interference could block the Leu27IGF-II-induced cell apoptosis. Together, this study provides a new insight into the effects of the IGF-IIR and its downstream signaling in myocardial apoptosis. Suppression of IGF-IIR signaling pathways may be a good strategy for both the protection against myocardial cell apoptosis and the prevention of heart failure progression.
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PMID:Activation of insulin-like growth factor II receptor induces mitochondrial-dependent apoptosis through G(alpha)q and downstream calcineurin signaling in myocardial cells. 1909 37

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and NTproBNP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.
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PMID:The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease. 1938 Feb 80

Cardiac hypertrophy is one of the main ways in which cardiomyocytes respond to mechanical and neurohormonal stimuli. It enables myocytes to increase their work output, which improves cardiac pump function. Although cardiac hypertrophy may initially represent an adaptive response of the myocardium, ultimately, it often progresses to ventricular dilatation and heart failure which is one of the leading causes of mortality in the western world. A number of signaling modulators that influence gene expression, apoptosis, cytokine release and growth factor signaling, etc. are known to regulate heart. By using genetic and cellular models of cardiac hypertrophy it has been proved that pathological hypertrophy can be prevented or reversed. This finding has promoted an enormous drive to identify novel and specific regulators of hypertrophy. In this review, we have discussed the various molecular signal transduction pathways and the regulators of hypertrophic response which includes calcineurin, cGMP, NFAT, natriuretic peptides, histone deacetylase, IL-6 cytokine family, Gq/G11 signaling, PI3K, MAPK pathways, Na/H exchanger, RAS, polypeptide growth factors, ANP, NO, TNF-alpha, PPAR and JAK/STAT pathway, microRNA, Cardiac angiogenesis and gene mutations in adult heart. Augmented knowledge of these signaling pathways and their interactions may potentially be translated into pharmacological therapies for the treatment of various cardiac diseases that are adversely affected by hypertrophy. The purpose of this review is to provide the current knowledge about the molecular pathogenesis of cardiac hypertrophy, with special emphasis on novel researches and investigations.
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PMID:Molecular targets and regulators of cardiac hypertrophy. 1996 85

Endothelin (ET-1) is the polypeptide about wide spectrum of physiological effects. The results of numerous experimental and clinical investigations showed its essential role also in the pathophysiology of various cardiovascular diseases (arteriosclerosis, heart failure, pulmonary hypertension, renal failure) and some neoplastic conditions. Thus, ET-1 blocking becomes an interesting tool of modern pharmacotherapy, targeted on neurohormonal mechanisms. The article briefly describes biochemical properties of ET-1 and ET and pathophysiological role of ET-1 in selected cardiovascular diseases.
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PMID:[Endothelin in cardiovascular diseases pathophysiology]. 2049 39

Resistin, a 12.5-kDa polypeptide, has been associated with both insulin resistance and inflammation in animal models. Although initially discovered in the adipocytes, it has subsequently been found in other tissues. In humans, controversy still exists regarding the role of resistin but serum resistin concentration has been correlated with risk factors for coronary heart disease, renal dysfunction and outcomes among stroke patients. Both inflammation and insulin resistance are associated with the development of incident heart failure, with worse outcomes among those with prevalent cardiomyopathy. Therefore, it is interesting to note that recent literature suggests a significant relationship between serum resistin concentrations and heart failure. In this article, we discuss the physiology, pathophysiology, and the direct and indirect role of resistin in determining heart failure risk and worse outcomes among these patients. Some of the salient points reviewed include the possible association of resistin with hyperglycemia and substrate metabolism, inflammation through TNF-alpha and direct cardiac effects.
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PMID:Serum resistin: physiology, pathophysiology and implications for heart failure. 2055 Apr 78

Icariin, the primary active component of Epimedium extracts, has recently been shown to induce cardiomyocyte differentiation of murine embryonic stem (mES) cells in vitro. However, as these cardiomyocytes were not functionally characterized, the potential application of icariin-induced cardiomyocytes in clinical practice remains unclear. Therefore, in this study, we characterized the structure and function of icariin-induced cardiomyocytes to evaluate their potential application in transplantation for cardiac failure treatment. mES cells were cultured as embryoid bodies (EBs) via the direct suspension method in the presence of icariin. The protein expression profiles and ultrastructural characteristics of mES cell-derived cardiomyocytes were then characterized by immunofluorescence and transmission electron microscopy, respectively. In addition, the expression of cardiac-specific and calcium handling genes was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cardiomyocytes induced by icariin treatment expressed the cardiac-specific proteins myosin light chain-1v (MLC1v), atrial natriuretic polypeptide (ANP), and cardiac troponin I (cTnI). Furthermore, these cells appeared to possess myofibrils organized into mature sarcomeres that had formed A and I bands. In addition, icariin treatment upregulated the mRNA levels of MLC1v, ANP, cTnI, calsequestrin (CSQ), and sodium-calcium exchanger (NCX) in these cells. Icariin induces the differentiation of mES cells into beating cardiomyocytes with normal structure and function. Therefore, these cells may have promising applications in cardiac cell therapy or tissue engineering.
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PMID:Icariin induces mouse embryonic stem cell differentiation into beating functional cardiomyocytes. 2118 Dec 38


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