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

A study of myosin extracted from dog's cardiac muscle at different stages of chronic heart failure (from 1 week to 1 year) was carried out. A decrease of UV-luminescence intensity, flow birefringence and ATPase activity (to 70%) was observed. The electron microscopic investigation of myosin and LMM structure shows the loss of ability to form typical paracrystals by LMM, the electron microscopic appearance of the whole myosin being unchanged.
 ...
PMID:[Structural and functional changes in myosin in chronic coronary insufficiency]. 13 86

The Ca2+-activated myosin ATPase and the amino acid compositions of actin and myosin were determined for preparations from chronically failing dog hearts. Hypertrophy and congestive heart failure were produced by combined tricuspid valve insufficiency and pulmonary artery stenosis. Control, shamoperated, and noncardiac circulatory failure (inferior vena cava constriction) dogs also were studied. All hearts were divided into right ventricle, septum and left ventricle and each sample was individually analyzed. Calcium-activated ATPase decreased in the failing hearts and showed a distinct gradient of depression from right to left ventricles. There were no changes in ATPase activity among the other groups. The amino acid composition of actin was the same regardless of origin. The amino acid composition of myosin was unaltered except that cystine/2 residues were markedly decreased in failing heart myosin. The same gradient of depression was present as was found for Ca2+-activated myosin ATPase. This study suggests that protein metabolism is abnormal and that altered proteins are produced in hypertrophy and congestive heart failure. It appears that these changes do not affect all proteins, since actin was normal by the parameters studied. It is clear that the stressed ventricle is the most severely involved, but the entire heart is altered to some degree. Thus, we conclude that altered protein metabolism may be an important primary factor in the genesis of heart failure.
 ...
PMID:The amino acid composition of actin and myosin and Ca2+-activated myosin adenosine triphosphatase in chronic canine congestive heart failure. 13 12

The effects of low protein diet on cardiac metabolic and structural changes subsequent to an extremely high pressure load were investigated. Spontaneously hypertensive rats(SHR) were divided into four groups, and fed the following diets for four weeks: 1) Group A: regular diet (23% protein) and water, 2) Group B: regular diet and 1% saline, 3) Group C: low protein diet (10% protein) and water, and 4) Group D: low protein diet and 1% saline. Two weeks after the start of feeding, there was no significant difference in the left ventricular ultrastructures between the corresponding regular and low protein diet groups. Four weeks after, degenerative findings such as streaming of Z lines, dilatations of smooth endoplasmic reticulum, and disarrangements of myofilaments appeared Group D, while in Group B electron microscopic findings indicated hypertrophy. Incorporation of [14C] leucine into the myocardial myosin B in Group D was significantly low, with a resulting fall of the LVdP/dtmax per integrated isometric pressure (IIP) and a rise of the left ventricular end-diastolic pressure (LVEDP), as compared to that in Group C at four weeks after the start of feeding. These observations suggest that, in the heart with an extremely high pressure load, low protein diet hinders the development of hypertrophy to the load with resulting heart failure.
 ...
PMID:Effect of low protein diet on cardiac function and ultrastructure of spontaneously hypertensive rats loaded with sodium chloride. 103 68

Cardio- and hemodynamics was investigated in 69 patients with chronic coronary insufficiency without manifestations of cardiac decompensation and with symptoms of congestive incompetence of the heart by using radiocardiography and analyzing systolic phases of the left ventricle. Furthermore, fractional composition of myocardial proteins and the ATP-ase myosin activity were studied in 31 persons, who during their life-time suffered from ischemic heart disease. In patients presenting no symptoms of cardiac insufficiency significant changes in cardio- and hemodynamics along with a reduced content of the actomyosin complex proteins and their disturbed ATP-ase activity were uncovered. These changes proved more intensive in the face of manifestations indicating cardiac decompensation. Thus, a complex investigation of cardio- and hemodynamics enabled it to disclose initial disorders in the contractile activity of the myocardium in patients with chronic coronary insufficiency, when such disturbances are associated both with deranged utilization and with defective accumulation of energy in the myocardium.
 ...
PMID:[Contractile activity of the myocardium in chronic coronary insufficiency]. 123 9

End-stage human heart failure is the common final manifestation of a group of heterogeneous diseases, and it is usually accompanied by myocardial hypertrophy. Studies on animal models have shown that myocardial hypertrophy is an adaptational process accompanied by characteristic changes in the expression of cardiac genes: reinduction of fetal isoforms of the myofilaments actin and myosin, downregulation of SR Ca(2+)-ATPase and phospholamban, downregulation of beta-adrenoceptors and increased expression of inhibitory G proteins (Gi). These alterations lead to reduced shortening velocity, slowed relaxation, and to desensitization of adenylyl cyclase, thereby probably increasing myocardial economy and lowering energy demand. Gene expression in human end-stage heart failure due to dilated cardiomyopathy exhibits some clear differences, but also significant parallels to gene expression in experimental hypertrophy: there is no isoform shift because fetal isoforms of the myofilaments are already predominant in the adult ventricle. However, like in animal models expression of SR Ca(2+)-ATPase and phospholamban is decreased, correlating with slowed relaxation of the diseased myocardium, beta-adrenoceptors are downregulated, and the expression of Gi is increased, leading to desensitization of the adenylyl cyclase pathway. These results suggest that alterations of gene expression in human end-stage myocardial failure, known so far, are secondary to chronic overload and are not a primary cause in the pathogenetic process. They are probably initially favorable adaptive processes to chronic overload, but finally cause a further deterioration of contractile performance of the myocardium.
 ...
PMID:[Changes in gene expression in terminal myocardial failure]. 129 Mar 4

In the human ventricle two isoforms of the phosphorylatable myosin light chain (MPLC) are expressed. These two forms are designated with increasing acidity as LC-2 and LC-2*. In the normal human heart the relation between LC-2/LC-2*-expression is 70/30, suggesting the existence of three different myosin isoenzymes (MPLC-polymorphism) in the normal human ventricle. Both ventricular MPLC-isoforms are monophosphorylated, the LC-2 being higher phosphorylated than the LC-2*. In some patients with heart failure both MPLC isoforms were found to be completely dephosphorylated. In the human atrium a MPLC isoform is expressed which is different from the ventricular MPLC isoforms. The atrial MPLC isoform is mono- and diphosphorylated. Mono-phosphorylation of both the ventricular MPLC isoforms and the atrial MPLC isoform increased responsiveness as well as sensitivity of isometric tension generation of skinned fibers to Ca2+. Part of this effect could be explained by changing the cross-bridge-cycling rate: MPLC increased fapp, the rate-constant for the transition of cross-bridges from the non-force into the force-generating state, thus increasing the amount of force-generating cross-bridge states at a given [Ca2+]. Monophosphorylation of the MPLC isoforms did not change maximal shortening velocity.
 ...
PMID:Effects of different expression and posttranslational modifications of myosin light chains on contractility of skinned human cardiac fibers. 138 30

The role of subcellular alterations in the process of heart failure remains ill-defined. Because contractile performance of failing heart muscle is depressed, possible alterations in the myosin molecule could be of particular relevance. There is increasing evidence that myofibrillar ATPase activity is reduced in congestive heart failure, whereas the findings on myosin ATPase are still controversial. The molecular causes of the reduced activity are currently not known. Because alpha-MHC is present only in small amounts in normal ventricles, a shift in favor of beta-MHC is of minor importance. Also immunohistochemical data on subspecies of beta-MHC seem not to provide an explanation. A new type of myosin heterogeneity was found by optimizing native polyacrylamide gel electrophoresis in the presence of pyrophosphate. Two bands (VA and VB) were observed in ventricles of patients with valvular disease. Because the two bands were detected also in normal hearts of large mammals, the existence of VA/VB cannot be diagnostic of diseased heart. However, the VA/VB ratio was influenced by the hemodynamic load, whereby the fast migrating band (VA) increased with the diastolic and systolic load. Because a relationship with the hemodynamic load was observed only in surgical muscle specimens, it appears that this heterogeneity is prone to post mortem modification. Further work is required to identify the molecular nature of this heterogeneity and to examine the therapeutic potential of a pharmacological modification of the VA/VB ratio.
 ...
PMID:Structural and functional diversity of human ventricular myosin. 138 32

Chronic increases in haemodynamic load modify the expression of cardiac genes, leading to cardiac hypertrophy and a new phenotype. As an example, changes in the expression of the genes encoding the main contractile proteins, the isomyosin heavy chains, have been associated with modifications of the physiological properties of cardiac muscle. The cellular and molecular mechanisms which either do or do not initiate and maintain these changes in cardiac genomic expression remain to be elucidated. Using in situ hybridization we show that mRNAs encoding a cellular form of fibronectin (c-FN), a protein of the basal membrane which is not or poorly expressed in adult rat heart, are reexpressed as a result of severe hypertension with a similar time course than the beta-heavy chain of myosin (beta-MHC), also mostly expressed in fetal heart. The accumulation of the c-FN mRNAs was found in the wall of coronary arteries whilst that of the beta-MHC mRNAs occurred in the myocytes at the border zone of these arteries. Thus a high pressure in the arteries could be the trigger inducing the synthesis of factors which could, through a gradient, modulate the phenotype of both the smooth muscle cells of the media and the cardiocytes. Besides, using a model of cultured adult rat cardiocytes, we show that the differential expression of the MHC isoforms is dependent on the beta-adrenergic stimulation but that the regulation depends on the stage of development of the cells and differs for the alpha and beta MHC. These 2 complementary approaches for identifying the molecular mechanisms that control cardiac muscle growth should help for understanding cardiac adaptation triggered by haemodynamic overload, such as arterial hypertension as well as cardiac failure.
 ...
PMID:[Changes in heart genome expression in hypertensive diseases]. 149 74

In myocardial hypertrophy and heart failure a series of adaptational changes occur some multiplying contractile units, others slowing shortening velocity and increasing economy of contraction. The demonstration of energy-saving mechanisms in heart failure has prompted further investigations of energy providing and utilizing metabolic pathways. The use of myocardial ATP as a substrate occurs mainly at the myosin-ATPase and at the Ca-ATPase of the sarcoplasmic reticulum. As the Michaelis constant of both enzymes for ATP is in the micromolar (microM) range, whereas cellular ATP content is about 5000 microM, these enzymes are not controlled by the availability of ATP as a substrate. In experimental heart failure in large animals, normal or reduced creatine phosphate levels (in most cases together with normal adenine nucleotides) have been described. Reduced creatine phosphate is found in models with increased oxygen consumption, and creatine phosphate may buffer the ATP pool in these models. In human heart failure due to dilated cardiomyopathy, where resting oxygen consumption per unit mass and lactate extraction are normal in most patients, normal adenine nucleotides, creatine phosphate, and mitochondrial function have been described in the initial studies. These results have been challenged by one study showing decreased ATP levels in dilated cardiomyopathy, correlating with the decrease in ejection fraction. However, only ATP has been measured in this study, whereas total adenine nucleotides may be a more suitable parameter. Recently published results have again demonstrated normal ATP and total adenine nucleotides in human heart failure. In the same patients, significantly decreased myocardial norepinephrine was measured, indicating that metabolic changes had occurred in these hearts, but were independent of adenine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adenine nucleotide metabolism and contractile dysfunction in heart failure--biochemical aspects, animal experiments, and human studies. 149 76

In recent years, captopril has attracted considerable clinical attention as an agent for use in treating heart failure. We administered 15 mg/kg of captopril or 1.5 mg/kg of enalapril to 5-week-old J-2-N cardiomyopathic hamsters for 10 or 15 weeks, and investigated the roles of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the onset and progress of cardiomyopathy. In the untreated group, serum creatine kinase levels increased in accordance with the progression of cardiomyopathy, but this increase was markedly inhibited by the administration of captopril. The rise in serum aldolase levels was similarly inhibited. Serum malondialdehyde levels were significantly reduced by the administration of captopril. ECG findings and the ventricular myosin isoenzyme pattern were also markedly improved by captopril. The improvement in all these parameters was less with enalapril. These differences between captopril and enalapril suggest that increases in tissue bradykinin and vasodilatory prostaglandins may play an important role in the beneficial effects of captopril.
 ...
PMID:The effects of angiotensin converting enzyme inhibitors and the role of the renin-angiotensin-aldosterone system in J-2-N cardiomyopathic hamsters. 153 90


1 2 3 4 5 6 7 8 9 10 Next >>