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)

A decrease in the density of the beta 1-adrenergic receptor and an increase in the functional activity of the G inhibitory protein Gi accompany human heart failure; however, the molecular and biochemical mechanisms responsible for these changes are unclear. We previously reported that the steady-state levels of the mRNAs encoding both alpha Gi-3 and alpha Gs were significantly increased in failing human heart. However, these results are not consistent with recent studies demonstrating that immunodetectable levels of alpha G proteins are not different in failing human hearts when compared with non-failing controls. In addition, analysis of the 5' flanking regions of alpha Gi and alpha Gs suggests that these two genes are unlikely to be co-regulated as their regulatory domains are quite different. Therefore, we hypothesized that the disparity between the measurements of alpha G protein gene expression and assessment of the actual levels of alpha G proteins might be due to technical limitations of the Northern blot technique utilized in previous studies for assessment of the mRNA levels; (i) cytoskeletal beta-actin mRNA was used as a standard for normalization; and (ii) only relative levels of alpha G mRNAs were measured. The recent application of the polymerase chain reaction to quantification of mRNA levels in small quantities of human heart provided the tool with which to test this hypothesis. When expressed in molecules of mRNA per microgram of total RNA, there were no differences in the levels of alpha Gi and alpha Gs mRNAs in failing human heart when compared with non-failing controls.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1991 Dec
PMID:Expression of alpha-subunits of G proteins in failing human heart: a reappraisal utilizing quantitative polymerase chain reaction. 181 Oct 54

Sodium has been identified as a causal factor in the development of hypertension in experimental animal models as well as in clinical human subjects. Sodium is also known to play a role in modulating myocardial mass and its pattern of myosin isozyme distribution. In the rodent model, the accumulation of V3 myosin isozyme (MI), due to the modulating influence of sodium, has been shown to be associated with persistent cardiac hypertrophy and heart failure. In this paper, we have examined the effect of the restriction of dietary sodium on blood pressure, ventricular weight and myosin isoforms in spontaneously hypertensive rats (SHR) and the relationship of these parameters with age. In 10- to 11-week-old SHR, dietary sodium restriction for 14 weeks resulted in a significant reduction in ventricular mass associated with systolic shifting of myosin isoform from V3 type to V1 type with no change in systolic blood pressure level; dietary sodium restriction also showed a significant reduction in body weight. When the effect of dietary sodium restriction (for 8 weeks) was studied in relation to age (in 11-, 16- and 24-week-old rats) a significant shift in myosin isoform from the V3 to the V1 type was noted in the 11-week-old rats; a slight but significant shift was noted in 16-week-old rats, and no change in myosin isoform distribution was noted in the 24-week-old SHR. The alteration in myosin isoform and myocardial mass in the 11- and 16-week-old rats was independent of changes in systolic blood pressure. This study demonstrates that sodium plays an important role not only in modulating myocardial mass but also in changing the biochemical composition of the heart. This study also suggests that in genetic hypertension, the restriction of sodium at a very young age may fully prevent the development of hypertension and hypertrophy. However, the mechanism by which the sodium ion modulates myocardial mass and the expression of either V1 or V3 myosin genes is unknown; the question of how sodium affects the cardiac function also remains. Some evidence suggests that sympathetic outflow may play an important role, but further studies are needed to validate this.
J Mol Cell Cardiol 1991 Jun
PMID:Effect of sodium deprivation on cardiac hypertrophy in spontaneously hypertensive rats: influence of aging. 183 55

In the present study, the Ca2(+)-sensitivity and myosin light chain patterns of skinned fibers of right atrium and left papillary muscles of 27 patients suffering from mitral valve disease (MVD, moderate heart failure), ischemic cardiomyopathy (ICM, severe heart failure), dilated cardiomyopathy (DCM, severe heart failure), and coronary heart disease (CHD, no heart failure, no atrial hypertrophy) were investigated. Myosin light chains of both chemically skinned and intact samples were studied by two-dimensional gel electrophoresis (2D-PAGE). Ca2(+)-sensitivity of ventricular fibers was about 0.14 pCa-units higher than that of atrial fibers in all groups except dilated cardiomyopathy where this difference was markedly diminished (only 0.06 pCa-units). Generally, Ca2(+)-sensitivity of skinned ventricular fibers was the same among the different heart diseases. Skinned atrial fibers from patients with dilated cardiomyopathy, however, were significantly (about 0.08 pCa-units) more sensitive for Ca2+ than those of the other groups (coronary heart disease, mitral valve disease or ischemic cardiomyopathy) which showed similar Ca2(+)-tension relationships. Ventricle-specific P-light chain forms could be observed in atrial samples from patients of all groups, whereas no atrium-specific light chain forms were detectable in any ventricular sample. It is concluded that there is no difference in Ca2(+)-sensitivity of the ventricular contractile elements of the human heart in different heart diseases. In atrial myocardium, there is an increased Ca2(+)-sensitivity of skinned fibers from hearts with dilated cardiomyopathy which is probably related to an elevation of right atrial pressure.
J Mol Cell Cardiol 1990 Dec
PMID:Calcium sensitivity and myosin light chain pattern of atrial and ventricular skinned cardiac fibers from patients with various kinds of cardiac disease. 208 58

The aim of the present study was to investigate whether or not alterations of Gs alpha can be detected with cholera toxin-induced ADP-ribosylation in myocardial membranes from patients with heart failure. Therefore, Gs alpha was radiolabeled by cholera toxin-catalzyed (32P)ADP-ribosylation with (32P)NAD as substrate. In membranes from left ventricular myocardium of six patients with dilated cardiomyopathy classified as NYHA IV and three samples from two non-failing donor hearts, labeling was too weak to allow detection of possible changes in the amount of Gs alpha. Therefore, the cytosolic small molecular weight G protein ARF (ADP-ribosylation factor), a cofactor for cholera toxin-induced ADP-ribosylation of Gs alpha, was partially purified from bovine cerebral cortex. ARF activity was quantified by its ability to enhance auto-ADP-ribosylation of cholera toxin A1-subunit. Gs alpha was identified by comparing the ADP-ribosylation patterns of myocardial membranes, membranes prepared from human leukemia (HL 60) and S 49 mouse lymphoma wild type cells (45 kDa-band present) with membranes of the Gs alpha-deficient S 49 variant cyc- (45 kDa-band missing). In the presence of ARF, specific radiolabeling of the Mr 45,000 subtype of Gs alpha was markedly enhanced. The amounts of Gs alpha as measured by cholera toxin-dependent (32P)-ADP-ribosylation in the presence of ARR were similar in failing and nonfailing human hearts. It is concluded that factors other than Gs alpha are responsible for the altered regulation of the adenylate cyclase complex in heart failure. Moreover, by enhancing cholera toxin-catalyzed ADP-ribosylation, endogenous ADP-ribosylation factor from bovine brain appears to be a useful tool to study Gs alpha even in tissues in which the labeling of Gs alpha is rather weak.
J Mol Cell Cardiol 1990 Jan
PMID:Improvement of cholera toxin-catalyzed ADP-ribosylation by endogenous ADP-ribosylation factor from bovine brain provides evidence for an unchanged amount of Gs alpha in failing human myocardium. 210 80

In this study we tested the hypothesis that reduced myofibrillar ATPase activities in end-stage heart failure are associated with a redistribution of myosin isozymes. Cardiac myofibrils were isolated from left ventricular free wall from normal human hearts and hearts at end-stage heart failure caused by coronary artery diseases, cardiomyopathy or immunological rejection. The hearts had been excised in preparation for a heart transplant. Myofibrillar Ca2(+)-dependent Mg-ATPase and myosin Ca2(+)- and K+EDTA-ATPase activities were compared. Possible changes in myosin isozyme distribution in the diseased heart were investigated using polyacrylamide gel electrophoresis of native myosin in the presence of pyrophosphate. Significant reduction in myofibrillar Ca2(+)-dependent Mg-ATPase with no changes in the sensitivity of the myofibrils to Ca2+ was observed in heart with coronary artery diseases (25.2 to 27.1% at pCa 5.83 to pCa 5.05), cardiomyopathy (21.1 to 25.5% at pCa 5.41 to pCa 5.05), and in the immunologically rejected heart (18.4 to 22.8% at pCa 5.41 to pCa 5.05). Significantly lower myosin Ca2(+)-ATPase was observed with coronary artery diseases only and myosin K-EDTA activities did not differ in diseased and normal hearts. Polyacrylamide gel electrophoresis of native myosin from the normal and three models of end-stage heart failure revealed two distinct bands in the human left ventricle and one diffuse band in the human right atria. No apparent differences in myosin isoenzyme pattern were observed between the normal and diseased hearts. Further evaluation is needed to clarify the ATPase nature of the two bands.
Mol Cell Biochem 1990 Jul 17
PMID:Reduced cardiac myofibrillar Mg-ATPase activity without changes in myosin isozymes in patients with end-stage heart failure. 214 90

Alterations of cardiac contractility caused by thiamine deficiency were studied on three groups of 2 month old male Wistar rats: B1, fed a thiamine deficient diet, PF pair fed, which received an amount of thiamine free diet determined on the daily consumption of B1 animals, supplemented with appropriate thiamine supply, C ad libitum fed controls. The animals were studied after 35 days of dietary treatment. Force-velocity curves were determined in right ventricle papillary muscles. Shortening velocity was significantly lower in B1 and PF than in C muscles and in B1 than in PF muscles. The ability to develop tension was not altered. Myosin ATPase activity was assayed in preparations of myofibrils and in preparations of purified myosin. Both Ca-Mg activated myofibrillar ATPase activity and Ca-activated myosin ATPase activity were significantly reduced in B1 and PF compared to C myocardium. Furthermore Ca-activated ATPase activity was lower in B1 than in PF myocardium. Myosin isoenzyme distribution was determined by pyrophosphate gel electrophoresis of purified myosin preparations. When compared to C animals both B1 and PF animals showed a myosin electrophoretic pattern shifted towards the slow isoform V3; such a shift was more pronounced in B1 animals. Information concerning excitation-contraction coupling was obtained by determining the steady state and transient force-interval relation and by recording transmembrane action potential. B1 and PF myocardium exhibited, when compared to C, a less sensitivity to a reduction of the interval of stimulation, a faster mechanical restitution, a prolonged action potential duration. Such alterations were generally more pronounced in B1 than in PF myocardium. The results support the view that in the rat cardiac contractility is deeply affected by thiamine deficiency. The alterations of cardiac contractility seem to be caused by adaptive mechanisms rather than by cardiac failure and seem to be attributable for a big part to the reduction of food supply.
J Mol Cell Cardiol 1990 Oct
PMID:Altered contractile properties of rat cardiac muscle during experimental thiamine deficiency and food deprivation. 215 36

Heart failure is common among the elderly and an alteration in myocardial Ca2+ transport is believed to be involved in its depressed contractile performance. Although ATP-dependent sarcoplasmic reticular (SR) Ca2+ transport has been reported to decrease in old hearts, virtually nothing appears to be known about the Ca2+ pump activity of SR in aging myocardium in the presence of calmodulin, one of its endogenous activators. In this study, the activity of the Ca2+ pump of aging cardiac SR was assessed in the presence of this endogenous stimulator. This assessment was therefore designed to give additional information about the status of this enzyme in old hearts. Male Sprague-Dawley rats were used and were divided into 3 groups: young (4-6 months old); middle-aged (15-17 months old) and old age (24-25 months old). Purified SR membranes were isolated from ventricular tissues. ATP-dependent Ca2+ accumulation by membrane vesicles of middle-aged and old hearts was significantly depressed in comparison to young hearts at all Ca2+ concentrations employed in the absence and presence of calmodulin. The activity of this Ca2+ transporter was similar in middle-aged and old hearts even in the presence of calmodulin. These results suggest that the activity of the Ca2+ pump in SR of aging hearts is depressed even in the presence of calmodulin.
Mol Cell Biochem 1989 Jan 23
PMID:Effect of calmodulin on sarcoplasmic reticular Ca2+-transport in the aging heart. 252 44

The interstitium of the myocardium is composed of predominantly type I collagen; type III collagen is present to a lesser extent. The fibrillar collagens serve as tethers between muscle cells, muscle fibers, and blood vessels while also providing a scaffolding that supports the muscular and vascular compartments. In pressure overload hypertrophy, a continuous structural remodeling of the fibrillar collagen matrix is seen. What is initially an adaptive process that enhances tensile strength can eventuate in pathologic hypertrophy with muscle fiber entrapment, cell loss, and abnormal diastolic and systolic stiffness of the myocardium. Morphologically distinct patterns of myocardial collagen accumulation, or fibrosis, have been identified based on the alignment of thick and thin collagen fibers to one another and to cardiac muscle. Each pattern, representing either a reactive (without necrosis) or reparative process, can alter stiffness in a unique manner. The manner in which the interstitium regulates the nature and proportion of fibrillar collagen formation is unknown and deserving of further study. Such information may lead to the development of antifibrotic agents that counteract, prevent or modify disproportionate collagen remodeling in pressure overload hypertrophy. These agents may thereby ultimately represent corrective forms of therapy for the management of heart failure.
J Mol Cell Cardiol 1989 Dec
PMID:Patterns of myocardial fibrosis. 253 37

Rats treated with the alkaloid monocrotaline developed right ventricular hypertrophy with a left:right ventricle weight ratio of 1.35 +/- 0.10 (mean +/- s.e.m., n = 25) compared with 3.83 +/- 0.40 (n = 14) in diet-matched controls (P less than 0.001). Urine volume and sodium content were reduced and body water increased consistent with heart failure. In 10 out of 26 treated rats pleural, pericardial or peritoneal effusions were present. Urine norepinephrine content was significantly raised (P less than 0.02) but epinephrine was unchanged. Plasma norepinephrine levels were raised though not significantly. Myocytes isolated from the right ventricle had a reduced myosin Ca2+-activated ATPase (P less than 0.05) activity and a shift towards slower V2 and V3 myosin isoforms. There was no decrease in maximum contraction amplitude with calcium or isoproterenol in either left or right ventricular cells of treated rats. Right ventricular cells from treated rats showed a reduced rate of contraction in maximum isoproterenol (P less than 0.05) and a significant rightward shift in PD2 (P less than 0.05) representing a two-fold increase in EC50 for isoproterenol compared with right ventricular cells from control animals. There was no shift in EC50 for isoproterenol in left ventricle cells. In parallel experiments, myocytes isolated from both ventricles of rats treated with isoproterenol for one week showed a rightward shift of more than 50-fold in the isoproterenol concentration-response curve and a depressed response to maximum isoproterenol. In the rat monocrotaline model of right-sided cardiac hypertrophy and failure, changes in sensitivity to beta-adrenoceptor agonists are slight, and present only in the right ventricle. The lack of change in the left ventricle seems to suggest that this functional desensitisation is not a consequence of raised circulating catecholamines.
J Mol Cell Cardiol 1989 Oct
PMID:Isoproterenol sensitivity of isolated cardiac myocytes from rats with monocrotaline-induced right-sided hypertrophy and heart failure. 255 26

Prenalterol (beta 1-agonist), denopamine (beta 1-agonist), and zinterol (beta 2-agonist) were partial agonists of adenylate cyclase (AC) stimulation in human ventricular myocardium obtained from nonfailing chambers whose beta 1/beta 2 receptor subtype ratio was approximately 80/20. At a concentration less than its low affinity (beta 2) Kl, betaxolol, a highly selective beta 1-antagonist, inhibited isoproterenol (non-selective agonist), denopamine, and prenalterol stimulation of AC, indicating that isoproterenol, denopamine, and prenalterol are all capable of stimulating AC through beta 1-receptor activation. At a concentration less than its low affinity (beta 1) Kl, ICI 118,551, a highly selective beta 2-agonist, inhibited both isoproterenol and zinterol stimulation of AC, indicating that isoproterenol and zinterol stimulate AC through beta 2-receptors. Zinterol stimulation of AC was mediated entirely by beta 2-receptors, inasmuch as 10(-7) M betaxolol had no effect on the zinterol dose-response curve and ICI 118,551 produced a degree of blockade (KB = 5.2 +/- 1.6 X 10(-9) M), consistent with the beta 2-receptor Kl of the latter (2.0 +/- .4 X 10(-9) M, p, not significant). In nonfailing myocardium, analysis of beta 1 versus beta 2 stimulation by the nonselective agonist isoproterenol revealed that the numerically small (19% of the total) beta 2 fraction accounted for the majority of the total adenylate cyclase stimulation. In failing ventricular chambers with a beta 1/beta 2 receptor subtype ratio reduced from 82/19 (nonfailing) to 64/36 (p less than 0.001) and a beta 1-receptor density reduced by 61% (p less than 0.001), maximal denopamine stimulation was reduced by 49% (p less than 0.001). Moreover, in preparations from failing heart, the component of denopamine stimulation that was inhibited by 10(-7) M betaxolol (beta 1 component) was reduced by 77% (p less than 0.05). Finally, in preparations derived from failing ventricular myocardium, beta 2-receptor density was not significantly decreased, but zinterol stimulation of AC was reduced by 32% (p less than 0.05). We conclude that heart failure results in subsensitivity to both selective beta 1 and beta 2 stimulation of adenylate cyclase, with beta 1 subsensitivity due to selective beta 1 receptor down-regulation and beta 2 subsensitivity due to partial uncoupling of beta 2 receptors from subsequent events in the beta 2-adrenergic pathway.
Mol Pharmacol 1989 Mar
PMID:Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. 256 29


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