Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 55-year-old Asian man first visited to our hospital with complaining of exertional dyspnea eight years ago, and was diagnosed as having idiopathic dilated cardiomyopathy. One of his siblings also suffered from idiopathic dilated cardiomyopathy. His symptoms became worse gradually, and he was hospitalized again because of disturbance of consciousness on February 21, 2001. Hemodynamic monitoring with a Swan-Ganz catheter was started, which revealed that the cardiac index was 1.1 L/ min/BSA, cardiac output 1.8 L/min, and pulmonary artery pressure 43/33 mmHg. The echocardiographic observation showed that the left ventricular ejection fraction was 32%, and serum BNP was elevated to 5,411 pg/mL. Multi-organ failure including renal and hepatic dysfunction developed because of the low cardiac output status. Continuous hemodiafiltration (CHDF) was introduced to reduce the volume overload, improve renal failure, and eliminate adverse cytokines. Although his hemodynamic status was temporarily improved after starting CHDF, weaning from CHDF was difficult and he finally died from cardiogenic shock after two month of intensive therapy. The autopsy showed thinning of the left ventricular wall, and histological examination revealed diffuse fibrous hyperplasia and myocardial fiber deficit in the ventricular myocardium. CHDF was effective in reducing the volume overload and improving renal function; however, heart transplantation is inevitable for the patients with severe heart failure due to dilated cardiomyopathy.
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PMID:A case of dilated cardiomyopathy with end-stage heart failure treated by prolonged continuous hemodiafiltration. 1237 48

The angiotensin II type 2 (AT2) receptor is upregulated in the left ventricle in heart failure, but its pathophysiological roles in vivo are not understood. In the present study, AT2 receptors were expressed in transgenic (TG) mice using the ventricular-specific myosin light-chain (MLC-2v) promoter. In TG compared with nontransgenic (NTG) mice, in vivo left ventricular (LV) systolic pressure and peak +dP/dt were depressed while LV diastolic pressure was elevated (P < 0.05). Echocardiography showed severely depressed LV fractional shortening, increased systolic and diastolic dimensions, and wall thinning (P < 0.05). Confocal and electron microscopy studies revealed an increase in the size of myocytes and interstitial spaces as well as an increase in interstitial collagen, disruption of the Z-band, and changes in cytochrome c localization. The changes were most prominent in the highest-expressing TG line, which implies a dose-response relationship. AT2 overexpression was also directly associated with the increase of phosphorylated protein levels of PKC-alpha, PKC-beta, and p70S6 kinase. These data demonstrate that ventricular myocyte-specific expression of AT2 receptors promotes the development of dilated cardiomyopathy and heart failure in vivo.
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PMID:Ventricular-specific expression of angiotensin II type 2 receptors causes dilated cardiomyopathy and heart failure in transgenic mice. 1286 76

The tyrosine kinase receptor erbB2, also known in humans as Her2, is a member of the epidermal growth factor receptor (EGFR or erbB1) family, which also includes erbB3 and erbB4. The erbBs were discovered in an avian erythroblastosis tumor virus and exhibited similarities to human EGFR (Yarden and Sliwkowski, 2001). Her2/erbB2 is highly expressed in many cancer types. Its overexpression is correlated with a poor prognosis for breast and ovarian cancer patients. ErbB receptors bind to a family of growth factors, termed neuregulins/heregulin (NRG/HRG), which comprise NRG-1, -2, -3, and -4 and include multiple isoforms. ErbB2/Her2 is an orphan receptor that does not bind ligand alone but heterodimerizes with the other erbB receptors for NRG signaling. ErbB2 is expressed in multiple neuronal and non-neuronal tissues in embryos and adult animals, including the heart. Genetic data demonstrated that erbB2 is required for normal embryonic development of neural crest-derived cranial sensory neurons. ErbB2/Her2-null mutant embryos of a trabeculation defect die before embryonic day (E) 11. To study its role at later stages of development, we generated a transgenic mouse line that specifically expresses the rat erbB2 cDNA in the heart under the control of the cardiac-specific alpha-myosin heavy chain promoter. When crossed into the null background, the expression of the rat erbB2 cDNA rescued the cardiac phenotype in the erbB2-null mutant mice that survive until birth but display an absence of Schwann cells and a severe loss of both motor and spinal sensory neurons. To study the role of erbB2 in the adult heart, we generated conditional mutant mice carrying a cardiac-restricted deletion of erbB2. These erbB2 conditional mutants exhibited multiple independent parameters of dilated cardiomyopathy, including chamber dilation, wall thinning, and decreased contractility. Interestingly, treatment of breast cancers overexpressing erbB2 with Herceptin (Trastuzumab), a humanized monoclonal antibody specific to the extracellular domain of erbB2, results in some patients developing cardiac dysfunction. The adverse effect is increased significantly in those patients who also receive the chemotherapeutical agent anthracycline. We found that erbB2-deficient cardiac myocytes are more susceptible to anthracycline-induced cytotoxicity. These results suggest that erbB2 signaling in the heart is essential for the prevention of dilated cardiomyopathy. These lines of mice provide models with which to elucidate the molecular and cellular mechanisms by which erbB2 signaling regulates cardiac functions. These mice also will provide important information for devising strategies to mitigate the cardiotoxic effects of Herceptin treatment, allowing for the potential expanded use of this drug to treat all cancers overexpressing erbB2.
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PMID:Essential roles of Her2/erbB2 in cardiac development and function. 1474 94

The pulmonary arterioles react to hypoxia by contraction and to increased pressure and volume by hypertrophy of the muscular wall, referred to as pulmonary vascular remodeling, both of which increase vascular resistance and result in increased pulmonary arterial pressure. Heart muscle reacts to increased pressure by hypertrophy of cardiac myocytes and thickening of the muscular wall. The heart responds to increased volume by dilation of the chamber that may result in physiologic or pathologic hypertrophy of the muscle wall. Heart muscle cells are very sensitive to hypoxia or other insults, and this may result in death of individual cardiac myocytes with lengthening and thinning of the remaining heart muscle cells and dilation of the chamber in a process called dilated cardiomyopathy.
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PMID:The response of the heart and pulmonary arteries to hypoxia, pressure, and volume. A short review. 1743 39

This study was performed to elucidate the relation between in vivo measurements of two-dimensional principal strains and the progression of left ventricle (LV) wall thinning during development of dilated cardiomyopathy in the protein kinase C-epsilon (PKC-epsilon) transgenic (TG) overexpressing mouse heart. Principal two-dimensional strains, E1 and E2, were determined in the LV wall of the anesthetized mouse using cardiac MRI tagging at 14.1 T. PKC-epsilon TG provided a model of pure dilated cardiomyopathy without evidence of hypertrophy (PKC-epsilon TG, n = 6). Ejection fraction, wall thickness, and principal strains were determined at 1-mo intervals in hearts of PKC-epsilon TG vs. age-matched, nontransgenic mice (NTG, n = 5) from age 6 to 13 mo. Through the study, PKC-epsilon TG displayed lower ejection fraction than NTG. At 7 mo, average principal strain E1 in PKC-epsilon TG hearts was lower compared with NTG (PKC-epsilon TG = 0.14 +/- 0.03, NTG = 0.19 +/- 0.03, P < 0.05). The greatest reductions in regional E1 occurred in the lateral segments. The principal strain E2 did not change significantly in either group. At 9 mo, LV wall thinning occurred in PKC-epsilon TG mice (P < 0.01 vs. 8 mo) to 21% below values in NTG (P < 0.001). Average E1 strain diverged between PKC-epsilon TG and NTG hearts by 25-43%. These E1 changes preceded LV wall thinning and predated the eventual transition from a compensated circumstance to the dilated phenotype. The findings indicate a near step function in E1 depression that precedes the onset of LV wall thinning and suggest E1 as a prognostic indicator of dilated cardiomyopathy.
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PMID:Principal strain changes precede ventricular wall thinning during transition to heart failure in a mouse model of dilated cardiomyopathy. 1796 77

Discrepancies exist regarding potential sex differences in the effects of ethanol on the myocardium. Therefore, the aims of this study were to determine if long-term ethanol consumption was associated with the development of a dilated cardiomyopathy (CM) in female rats and, second, to determine if the absence of ovarian hormones modulated this effect. Adult male and female (n=6-8/group) sham-operated and ovariectomized (OVX) Sprague-Dawley rats received the Lieber DeCarli ethanol-containing (8% vol/vol) or control liquid diet for 8 months. All ethanol groups showed echocardiographic evidence of a cardiomyopathy; however, more significant ethanol-elicited differences were found in the male ethanol group than in either the female or female OVX groups. In addition, the male ethanol group had significant reductions in in vivo measures of contractility, such as the maximum derivative of change in systolic pressure and preload recruitable stroke work. Sex differences were also apparent in the pattern and degree of posterior and septal wall thickness changes, in that the male ethanol group had more posterior and septal wall thinning. In conclusion, similar to male rats long-term ethanol consumption in gonad-intact and OVX female rats is associated with the development of a dilated cardiomyopathy.
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PMID:Long-term effects of alcohol consumption in male and female rats. 1799 Jan 29

Cardiac tagging resolution for regional principal strains E1 and E2 has been a limiting factor for the study of dilated mouse hearts, in which the left ventricle (LV) wall thickness can drop to below 1 mm. Therefore, high resolution tagging was performed at 14.1 T to enable transmural principal strain measurements across the LV wall of normal mouse hearts and average principal strains in thinned LV walls of a transgenic mouse (PKCepsilon TG) that develops dilated LV. A modified DANTE tagging and fast gradient imaging method produced a tagging grid dimension of 0.33 x 0.33 mm and line thickness under 0.1 mm. In normal mice, average E1 strain in the epicardium was significantly higher than the endocardial E1 (epi = 0.22 +/- 0.10; endo = 0.13 +/- 0.07, p < 0.05), while magnitude of average endocardial E2 was greater than in the epicardium (endo = -0.12 +/- 0.03, epi = -0.08 +/- 0.03; p < 0.001). E1 strain averaged over four segments was reduced in dilated hearts compared to controls (PKCepsilon TG = 0.14 +/- 0.02; control = 0.18 +/- 0.02, p < 0.01), with specific reductions in septal (33%) and lateral (31%, p < 0.01) segments. E2 strain was similar between dilated and control hearts at -0.11 +/- 0.01. Thus, improved tagging resolution demonstrates that stretch (E1), but not compression strains (E2), are reduced as a result of significant LV wall thinning in a mouse model of dilated cardiomyopathy.
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PMID:Improved cardiac tagging resolution at ultra-high magnetic field elucidates transmural differences in principal strain in the mouse heart and reduced stretch in dilated cardiomyopathy. 1806 48

This study examined the putative role of blood vessel pathology in the development of ascites in broilers. Major blood vessels (aorta, brachiocephalic arteries, pulmonary arteries, and vena cava) from normal commercial male broiler chickens, and broilers that developed congestive heart failure (CHF) with or without ascites were subjected to gross and microscopic examination. On cross-section, grossly, the arteries from normal broilers and those showing dilated cardiomyopathy without ascites appeared circular, with firm wall tone characteristic of the normal artery. In contrast, the arteries from ascitic broilers appeared flaccid and lacked elasticity, which was evidenced by collapsing, ellipsoid cross-sectional arterial lumen owing to the structural weakness of the arterial walls. Microscopically, ascitic broilers showed thinning or occasionally total loss of elastic elements in the arterial wall, and reduced network density of the structural matrix of the vascular wall, as well as increased thickness of fibers in vena cava. The structural changes seen in the major arteries from ascitic broilers are maladaptive, and as such would definitively impose an increased hemodynamic burden on the already failing heart pump. The changes in veins are indicative of pathological remodeling conducive to increased permeability of the vascular wall, particularly in the situation when a poorly distensible structure is further subjected to wall stress associated with increased pressure and volume overload. Taken together, increased hemodynamic burden and reduced structural density of the venous wall constitute conditions conducive for seepage and accumulation of ascitic fluid.
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PMID:Vascular remodeling and its role in the pathogenesis of ascites in fast growing commercial broilers. 1894 43

ABSTRAST: A 3-year-old boxer bitch was evaluated for syncope and exercise intolerance. Physical examination revealed tachypnea, tachyarrhythmia and pulse deficit. Echocardiography demonstrated right atrial dilatation, thinning and hypokinesis of the right ventricular wall and normal contractility of the left ventricle. Three months after the first onset of clinical symptoms, the dog developed signs of congestive right heart failure despite treatment, and euthanasia was performed because of refractory ascites. The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) was reached based of the clinical evolution of rapid progressive right ventricular heart failure and the particular form of isolated right atrial and right ventricular alterations without any echographic abnormalities of the pulmonic and tricuspid valves. Definitive confirmation was made by necropsy. In contrast to boxer type dilated cardiomyopathy (BDCM), dilatation occurred primary on the right atrium and ventricle and the right ventricular wall was thinner in subtricuspidal, apical and infundibular locations, similar to the "triangle of dysplasia" of human patient with ARVC. Histological lesions showed myocyte atrophy and replacement with adipose and fibrous tissue extended from the epicardium toward the endocardium in the right ventricle (RV) and right atrium (RA). In contrast to BDCM, where the lesions are multifocal, they take here the form of waves, with a large base against the epicardium and a spike towards the endocardium, known as lesions with a wave-front pattern, which are typical of ARVC. This report with supraventricular arrhythmias and echographic location in the RA and RV supports the hypothesis that ARVC is a progressive disease which may also have left ventricular free wall involvement if the patient lives long enough.
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PMID:Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in a Boxer. 1908 56

Friedreich's ataxia (FRDA) has been associated with both cardiac hypertrophy and to a lesser degree dilated cardiomyopathy. We have conducted a cross sectional magnetic resonance imaging (MRI) study of 25 patients with clinically and genetically confirmed FRDA and 24 healthy controls to analyse how disease parameters influence cardiac features in FRDA. MR cine imaging in the long and short axis planes was performed alongside clinical assessments. LV mass was most pronounced in FRDA patients with a larger genetic mutation (GAA1 repeats >600), earlier age of onset (<16years) and a shorter disease duration (<15 years). LV mass decreased with longer disease duration (>15 years), and independent of GAA1 repeat size and age of onset, suggesting cardiac thinning occurred with prolonged disease. Heart function was lower in patients with larger GAA1 repeat number and longer disease duration. Consequently, cardiac hypertrophy was more marked in FRDA patients with a larger GAA1 repeat number and younger age of onset, while prolonged disease duration was associated with lower LV mass and decreased heart function. It is important not only to understand the biochemical basis for these cardiac changes but also allow for these changes when assessing the effect of treatment of FRDA patients.
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PMID:Analysis of the factors influencing the cardiac phenotype in Friedreich's ataxia. 2046 1


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