Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Right ventricular (RV) hypertrophy is an important problem in congenital heart disease. We determined the alterations in phenotype that occur in the initial phase of RV hypertrophy and their possible correlations with the degree of hypertrophy. Therefore, we performed a differential proteomic profiling study on RV hypertrophy using an animal model of pulmonary artery banding (PAB) in parallel with hemodynamic characterization. The RV homogenates were subfractionated in myofilament and cytoplasmic proteins, which subsequently were separated by two-dimensional gel electrophoresis (2-DE), excised, and analyzed by mass spectrometry (MS). The cytoplasmic fraction showed expression changes in metabolic proteins, indicative of a shift from fatty acid to glucose as a substrate for energy supply. Up-regulation of three HSP-27s (1.9-, 1.7-, and 3.5-fold) indicated an altered stress response in RV hypertrophy. Detailed analysis by immunoblotting and MS showed that two of these HSP-27s were at least phosphorylated on Ser15. The myofilament fraction showed up-regulation of desmin and alpha-B-crystallin (1.4-and 1.3-fold, respectively). This alteration in desmin was confirmed by 1-DE immunoblots. Certain differentially expressed proteins, such as HSP-27, showed a significant correlation with the RV weight to the body weight ratio in the PAB rats, suggesting an association with the degree of hypertrophy.
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PMID:Proteomic changes in the pressure overloaded right ventricle after 6 weeks in young rats: correlations with the degree of hypertrophy. 1591 12

In many forms of congenital heart disease, the right ventricle (RV) is subject to abnormal loading conditions resulting in RV hypertrophy and remodeling. We determined the alterations in RV cytoplasmic proteomic phenotype that occur during prolonged periods of RV pressure overload. We performed a differential proteomic profiling study on RV hypertrophy using an animal model of various durations of pulmonary artery banding (PAB) in parallel with hemodynamic characterization. This hemodynamic evaluation showed that after 6, 12 and 20 weeks of PAB, the RV is in a compensated state of hypertrophy. Overall, the majority of protein changes were metabolism related indicating a shift towards the glycolytic pathway at the expense of beta-oxidation in the RV of the PAB animals. The changes in proteins related to the glycolytic pathway, exemplified by enolase and creatine kinase B-chain, tended to precede changes in beta-oxidation. In parallel, increases in stress chaperones, exemplified by several phosphorylated HSP-27 species, are present from the 6 week time point, whereas increases in antioxidant proteins, exemplified by peroxiredoxin 2 and 6, appear to be restricted to the 12 week time point. The p38 MAPK signal transduction pathway appears not to be activated. Observed protein changes are likely part of a protective mechanism against the development of RV failure.
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PMID:Time dependent changes in cytoplasmic proteins of the right ventricle during prolonged pressure overload. 1760 72

In congenital heart disease (CHD), mechanical wall stress by increased pulmonary artery pressure and pulmonary blood flow is believed to play a pivotal role in the pathogenesis of pulmonary plexogenic arteriopathy (PPA). The pathogenesis of this disease that involves significant pulmonary arterial remodelling, is, however, largely unknown. In the systemic circulation, upregulation of HSP-70 and HSP-27 in the arterial wall occurs in response to acute hypertension, whereas HSP-60 and increased titres of anti-HSP-60 antibodies are associated with atherosclerotic vessel disease. We looked for the involvement of HSPs in the stress response of pulmonary endothelial and vascular smooth muscle cells in different abnormal hemodynamic conditions in patients with CHDs. We analyzed the expression pattern of HSP-27, HSP-70 and HSP-60 in lung biopsies of 38 patients with CHD, using immunohistochemistry. These included 4 individuals with an essentially normal pulmonary circulation, who served as controls. Immunoreactivity against HSP-27 and also against HSP-70 was present in the pulmonary endothelium and vascular smooth muscle cells of patients and controls in a similar pattern. In contrast, expression of HSP-60 was absent in pulmonary arteries of both patients and controls. In patients with advanced PPA, cells within plexiform lesions showed strong staining for HSP-27 and HSP-70, but were again negative for HSP-60. The intensity of immunoreactivity against HSP-70 correlated inversely with medial thickness of pre-acinar arteries (r = -0.32; p = 0.04). Expression of HSP-27 and HSP-70 did not correlate with hemodynamic parameters, although immunoreactivity against HSP27 tended to be increased in cases with high pulmonary artery pressure (r = 0.37; p = 0.16) and was highest in patients with flow-associated pulmonary hypertension (p<0.01). HSP-27 and HSP-70, but not HSP-60 are engaged in the stress response of cells of small pulmonary arteries in pulmonary plexogenic arteriopathy. HSP-27 and HSP-70 are increasingly expressed in the advanced proliferative lesions of this disease.
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PMID:Pulmonary vascular remodeling in congenital heart disease: enhanced expression of heat shock proteins. 2036 11