Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxisome proliferator activator receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARgamma and other nuclear receptors. It has been identified as an integral component of a multiprotein thyroid hormone receptor-associated protein/vitamin D(3) receptor-interacting protein/activator-recruited cofactor complexes required for transcriptional activity. Here, we show that PBP is critical for the development of placenta and for the normal embryonic development of the heart, eye, vascular, and hematopoietic systems. The primary functional cause of embryonic lethality at embryonic day11.5 observed with PBP null mutation was cardiac failure because of noncompaction of the ventricular myocardium and resultant ventricular dilatation. There was a paucity of retinal pigment, defective lens formation, excessive systemic angiogenesis, a deficiency in the number of megakaryocytes, and an arrest in erythrocytic differentiation. Some of these defects involve PPARgamma and retinoid-sensitive sites, whereas others have not been recognized in the PPAR-signaling pathway. Phenotypic changes in four organ systems observed in PBP null mice overlapped with those in mice deficient in members of GATA, a family of transcription factors known to regulate differentiation of megakaryocytes, erythrocytes, and adipocytes. We demonstrate that PBP interacts with all five GATA factors analyzed, GATA-1, GATA-2, GATA-3, GATA-4, and GATA-6, and show that the binding of GATA-1, GATA-4, and GATA-6 to PBP is not dependent on the nuclear receptor recognition sequence motif LXXLL (where L is leucine and X is any amino acid) in PBP. Coexpression of PBP with GATA-3 markedly enhanced transcriptional activity of GATA-3 in nonhematopoietic cells. These observations identify the GATA family of transcription factors as a new interacting partner of PBP and demonstrate that PBP is essential for normal development of vital organ systems.
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PMID:Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors. 1172 81

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by progressive depression of myocardial contractile function and ventricular dilatation. Thirty percent of DCM patients belong to the inherited genetic form; the rest may be idiopathic, viral, autoimmune, or immune-mediated associated with a viral infection. Disturbances in humoral and cellular immunity have been described in cases of myocarditis and DCM. A number of autoantibodies against cardiac cell proteins have been identified in DCM. In this study, we have profiled the autoantibody repertoire of plasma from DCM patients against a human protein array consisting of 37,200 redundant, recombinant human proteins and performed qualitative and quantitative validation of these putative autoantigens on protein microarrays to identify novel putative DCM specific autoantigens. In addition to analyzing the whole IgG autoantibody repertoire, we have also analyzed the IgG3 antibody repertoire in the plasma samples to study the characteristics of IgG3 subclass antibodies. By combining screening of a protein expression library with protein microarray technology, we have detected 26 proteins identified by the IgG antibody repertoire and 6 proteins bound by the IgG3 subclass. Several of these autoantibodies found in plasma of DCM patients, such as the autoantibody against the Kv channel-interacting protein, are associated with heart failure.
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PMID:Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients and development of a disease-associated protein chip. 1641 13