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)

Very few tracers are available for imaging studies of second messenger systems. We developed a radiosynthesis for the phosphodiesterase (PDE) 5 inhibitor [(11)C]RAL-01. Whole body distribution studies using positron emission tomography (PET) revealed a time-dependant passage through the liver and accumulation of radioactivity in the bile of the Landrace pig. Displaceable binding was readily discerned in the myocardium, and traces of binding were seen in pulmonary tissue, consistent with the use of this class of drug in the treatment of pulmonary hypertension and heart failure. [(11)C]RAL-01 readily entered the brain and obtained an equilibrium distribution volume of 4-5 ml g(-1). Mean parametric images suggested the presence of a small displaceable binding component, but this binding was not significant in the present group of three pigs. Thus, [(11)C]RAL-01 shows considerable promise for PET studies of biliary elimination and of PDE5 binding in the cardiovascular system. However, analogues of higher affinity may be required for investigations of central nervous system binding sites.
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PMID:Synthesis, radiolabeling and in vivo evaluation of [11C]RAL-01, a potential phosphodiesterase 5 radioligand. 1684 33

Dilated cardiomyopathy (DCM) is an important cause of heart failure and sudden cardiac death worldwide. Transcription factor TBX20 has been shown to play a crucial role in cardiac development and maintenance of adult mouse heart. Recent studies suggest that TBX20 may have a role in pathophysiology of DCM. In the present study, we examined TBX20 expression in idiopathic DCM patients and in an animal model of cardiomyopathy, and studied its correlation with echocardiographic indices of LV function. Endomyocardial biopsies (EMBs) from intraventricular septal from the right ventricle region were obtained from idiopathic DCM patients (IDCM, n = 30) and from patients with ventricular septal defect (VSD, n = 14) with normal LVEF who served as controls. An animal model of DCM was developed by right renal artery ligation in Wistar rats. Cardiac TBX20 mRNA levels were measured by real-time PCR in IDCM, controls, and in rats. The role of DNA promoter methylation and copy number variation (CNVs) in regulating TBX20 gene expression was also investigated. Cardiac TBX20 mRNA levels were significantly increased (8.9 fold, p < 0.001) in IDCM patients and in RAL rats as compared to the control group. Cardiac TBX20 expression showed a negative correlation with LVEF (r = -0.71, p < 0.001) and a positive correlation with left ventricular end-systolic volume (r = 0.39, p = 0.038). No significant difference in TBX20 CNVs and promoter methylation was observed between IDCM patients and control group. Our results suggest a potential role of TBX20 in pathophysiology of DCM.
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PMID:Role of cardiac TBX20 in dilated cardiomyopathy. 2689 18