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)

In the present study, the potential of human adipose-derived stem cells to differentiate into cells with characteristics of cardiomyocytes was investigated. Adipose tissue-derived stem cells (ADSCs) were transduced with two different lentiviral vectors simultaneously: (1) a lentiviral vector expressing eGFP controlled by the Nkx2.5 promoter and (2) a lentiviral vector expressing DsRed2 controlled by the myosin light chain-2v promoter (MLC-2v). Nkx2.5-eGFP and MLC-2v-DsRed2 dual positive cells were isolated by FACS. Immunostaining and RT-PCR analysis of the dual positive cells revealed that these cells are positive for Nkx2.5, cardiac troponin I, and L-type calcium channel alpha-1c subunit. Electrophysiology studies demonstrated the presence of functional voltage-dependent calcium and potassium channels. These observations confirm that cardiac progenitor cells can be isolated and enriched from human adipose-derived stem cells using lentiviral selection, and they might represent a new source for cell therapy for myocardial infarction and heart failure.
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PMID:Genetically selected stem cells from human adipose tissue express cardiac markers. 1719 65

To investigate the feasibility of introcoronary cell infusion into nonischemic heart failure (HF) heart and whether different types of stem cell transplantation would affect heart function to a similar degree. Japanese white ears rabbits were used as HF models by intravenous injection adriamycin. Autologous bone marrow mononuclear cells(BMCs), bone marrow stromal cells (MSCs), skeletal myoblasts (SMs) or culture medium were infused into coronary arteries respectively by occluding the root of ascending aorta. The mortality during and 4 weeks after the procedure the mortality was 7.1% and 16.7% respectively. After 4 weeks, the ejection fraction (EF) in BMCs group had significant improvement (P < 0.05, n=8). No significant difference was seen in MSCs (n =8), SMs (n=6) and sham groups (n=8) compared with pretransplantation (P > 0.05). In sham group,the left ventricular endostolic diameter (LVED) had significant enlargement (P < 0.05), No significant difference was seen in MBCs, MSCs and SMs groups compared with pretransplantation (P > 0.05). Immunofluorescence revealed de novo expression of cardiac troponin I in BMCs and MSCs groups, cardiac troponin I was not detected in SMs group. In conclusions, intracoronary cell transplantation could provide effective cell delivery into dilated cardiomyopathy hearts and could be a useful strategy for treating CHF, BMCs cell transplantation may be the first choice in all the above cell types.
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PMID:[Changes of heart function after different cell type stem cell transplantation in chronic heart failure]. 1722 27

Congestive heart failure is the one of the major cardiovascular disorder that is increasing in incidence and cause of death globally. Mortality rate has increased 40%-50% in advanced cardiac failure and 15%-25% in mild to moderate cardiac failure within one year of diagnosis. There is no established biochemical marker for the diagnosis, prognosis and staging of heart failure. Cardiac Troponin I may be a novel useful tool in identifying patients with Heart failure who are at increased risk for progressive ventricular dysfunction and death. Thirty six congestive heart failure cases and thirty six healthy controls were included in this study and serum cardiac troponin I and Ejection fraction were measured. All the study subjects were grouped according to the NYHA class they belong. Cardiac troponin I was significantly higher in CHF cases than the controls. Troponin I also significantly differed among groups. EF of cases was significantly lower than the controls and also differed among groups. A significant negative correlation between cardiac troponin I and progressive decline of ejection fraction was evident in this study. Cardiac troponin I increased progressively with progression of heart failure. Thus, Cardiac troponin I could be used to stratify patients undergoing heart failure in to high and low risk groups for future cardiac events. Cardiac troponin I could also be used as a very important marker for the prognosis of the patients with congestive heart failure.
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PMID:Role of cardiac troponin I in staging and prognosis of congestive heart failure subjects. 1734 72

We have developed a mixed ester of hyaluronan with butyric and retinoic acid (HBR) that acted as a novel cardiogenic/vasculogenic agent in human mesenchymal stem cells isolated from bone marrow, dental pulp, and fetal membranes of term placenta (FMhMSCs). HBR remarkably enhanced vascular endothelial growth factor (VEGF), KDR, and hepatocyte growth factor (HGF) gene expression and the secretion of the angiogenic, mitogenic, and antiapoptotic factors VEGF and HGF, priming stem cell differentiation into endothelial cells. HBR also increased the transcription of the cardiac lineage-promoting genes GATA-4 and Nkx-2.5 and the yield of cardiac markerexpressing cells. These responses were notably more pronounced in FMhMSCs. FMhMSC transplantation into infarcted rat hearts was associated with increased capillary density, normalization of left ventricular function, and significant decrease in scar tissue. Transplantation of HBR-preconditioned FMhM-SCs further enhanced capillary density and the yield of human vWF-expressing cells, additionally decreasing the infarct size. Some engrafted, HBR-pretreated FMhMSCs were also positive for connexin 43 and cardiac troponin I. Thus, the beneficial effects of HBR-exposed FMhMSCs may be mediated by a large supply of angiogenic and antiapoptotic factors, and FMhMSC differentiation into vascular cells. These findings may contribute to further development in cell therapy of heart failure.
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PMID:Hyaluronan mixed esters of butyric and retinoic Acid drive cardiac and endothelial fate in term placenta human mesenchymal stem cells and enhance cardiac repair in infarcted rat hearts. 1736 74

The cardiac myofilaments are composed of highly ordered arrays of proteins that coordinate cardiac contraction and relaxation in response to the rhythmic waves of [Ca(2+)] during the cardiac cycle. Several cardiac disease states are associated with altered myofilament protein interactions that contribute to cardiac dysfunction. During acute myocardial ischemia, the sensitivity of the myofilaments to activating Ca(2+) is drastically reduced, largely due to the effects of intracellular acidosis on the contractile machinery. Myofilament Ca(2+) sensitivity remains compromised in post-ischemic or "stunned" myocardium even after complete restoration of blood flow and intracellular pH, likely because of covalent modifications of or proteolytic injury to contractile proteins. In contrast, myofilament Ca(2+) sensitivity can be increased in chronic heart failure, owing in part to decreased phosphorylation of troponin I, the inhibitory subunit of the troponin regulatory complex. We highlight, in this paper, the central role of the myofilaments in the pathophysiology of each of these distinct disease entities, with a particular focus on the molecular switch protein troponin I. We also discuss the beneficial effects of a genetically engineered cardiac troponin I, with a histidine button substitution at C-terminal residue 164, for a variety of pathophysiologic conditions, including hypoxia, ischemia, ischemia-reperfusion and chronic heart failure.
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PMID:Tuning cardiac performance in ischemic heart disease and failure by modulating myofilament function. 1739 43

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis. This may then result in cardiac remodelling. Serum biomarkers are available which can be used for diagnosis of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The problems with potential ischaemia markers are specificity and the reference diagnostic standard against which they can be judged. To date, only one, ischaemia-modified albumin(R), has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, have become recognised as the diagnostic reference standard for myocardial necrosis. The sensitive nature of these tests has also revealed that myocardial necrosis is also found in a range of other clinical situations, highlighting the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B-type natriuretic peptides can be shown to be diagnostic and prognostic in both ACS and detecting the sequelae of post-infarction myocardial insufficiency. The role of the B-type natriuretic peptides in detection of cardiac failure, both acute and chronic, is well defined but remains the subject of further studies, in ACS.
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PMID:Biomarkers of cardiovascular damage. 1754 Dec 89

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis and subsequent cardiac remodelling. Cardiac biomarkers can be used for diagnosis and assessment of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The challenges with potential ischaemia markers are specificity and the diagnostic reference standard for assessment. To date, only one, ischaemia modified albumin, has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, has become the diagnostic standard as the biomarker of myocardial necrosis. The sensitive nature of troponin measurement has also revealed that myocardial necrosis is also found in a range of other clinical situations. This illustrates the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B type natriuretic peptides can be shown to be diagnostic and prognostic for both acute ACS and detecting the sequelae of post infarction myocardial insufficiency. The role of the B type natriuretic peptides in detection of cardiac failure, acute and chronic, is well defined. Their role in ACS remains the subject of further studies.
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PMID:Biomarkers of cardiovascular damage and dysfunction--an overview. 1761 29

Despite evidence that cardiac troponin I (cTnI) identifies patients with advanced heart failure (HF) at risk of death, data on heterogeneous HF populations are scarce. Our purpose was to verify and analyze the prognostic role of cTnI in acute HF patients admitted to the emergency department. This was an observational longitudinal prospective study carried out in an urban hospital. We studied 99 patients discharged from the department between March and December 2002 with a HF diagnosis and samples of cTnI. Patients with acute coronary syndromes, myocarditis or renal failure were excluded. The main outcome was death from any cause. The detection level of the cTnI assay was 0.05 ng/ml. cTnI was detected in 45.5% of HF patients. These patients had a higher NYHA class (P<0.001) at initial presentation and longer hospitalization (P=0.004) than cTnI-negative patients. Nineteen deaths occurred during the study: 17 for HF and 2 for acute coronary syndrome. Finally, detectable cTnI was associated with increased mortality risk (RR 4.7; 95% CI 1.3-17.1; P=0.021) also after adjustment for other adverse prognosis factors (age, NYHA class and presence of relapses). Our HF cTnI-positive patients had a worse clinical presentation and longer hospitalization. cTnI is a significant independent predictor of death and of longer hospitalization. It could be used for the early identification of HF patients at an increased risk of death in the long term, and of longer hospitalization. Thus, cTnI can aid decision-making and clinical management in the emergency department.
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PMID:Cardiac troponin I as prognostic marker in heart failure patients discharged from emergency department. 1827 67

Transgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart (cTnI(193His) mice). The objective of this study was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function and pathophysiological changes were monitored in cTnI193His mice and wild-type littermates for a period of 12 mo. It progressed gradually from abnormal relaxation to diastolic dysfunction characterized with high-resolution echocardiography by a reversed E-to-A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. At the age of 12 mo, cardiac output in cTnI(193His) mice was significantly declined, and some transgenic mice showed congestive heart failure. The negative impact of cTnI193His on ventricular contraction and relaxation was further demonstrated in isolated mouse working heart preparations. The main morphological change in cTnI193His myocytes was shortened cell length. Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO. The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation characterized morphologically by enlarged atria and restricted ventricles and functionally by diastolic dysfunction and diastolic heart failure. The results demonstrate a critical role of the COOH-terminal domain of cTnI in the diastolic function of cardiac muscle.
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PMID:Impaired relaxation is the main manifestation in transgenic mice expressing a restrictive cardiomyopathy mutation, R193H, in cardiac TnI. 1840 33

Although beta-adrenergic stimuli are essential for myocardial contractility, beta-blockers have a proven beneficial effect on the treatment of heart failure, but the mechanism is not fully understood. The stimulatory G protein alpha-subunit (Gsalpha) couples the beta-adrenoreceptor to adenylyl cyclase and the intracellular cAMP response. In a mouse model of conditional Gsalpha deficiency in the cardiac muscle (Gsalpha-DF), we demonstrated heart failure phenotypes accompanied by increases in the level of a truncated cardiac troponin I (cTnI-ND) from restricted removal of the cTnI-specific N-terminal extension. To investigate the functional significance of the increase of cTnI-ND in Gsalpha-DF cardiac muscle, we generated double transgenic mice to overexpress cTnI-ND in Gsalpha-DF hearts. The overexpression of cTnI-ND in Gsalpha-DF failing hearts increased relaxation velocity and left ventricular end diastolic volume to produce higher left ventricle maximum pressure and stroke volume. Supporting the hypothesis that up-regulation of cTnI-ND is a compensatory rather than a destructive myocardial response to impaired beta-adrenergic signaling, the aberrant expression of beta-myosin heavy chain in adult Gsalpha-DF but not control mouse hearts was reversed by cTnI overexpression. These data indicate that the up-regulation of cTnI-ND may partially compensate for the cardiac inefficiency in impaired beta-adrenergic signaling.
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PMID:Removal of the N-terminal extension of cardiac troponin I as a functional compensation for impaired myocardial beta-adrenergic signaling. 1881 35


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