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)

The thyroid hormone receptors (TR) and the retinoic acid receptors share a high degree of homology and their signaling pathways interplay. Thyroid hormone (T3) is known to be associated with various pathological heart conditions. Retinoids are known to ameliorate symptoms in hyperthyroid patients. The aim of this study was to investigate if retinoic acid (RA) can have any effects on TR in cardiac cells and thus play a role in heart disease. Confluent AT-1 cardiomyocytes were treated with RA, T3 depleted medium and DITPA (a cardiotonic T3 analogue) for 48 hours. Solution hybridization for the determination of mRNA for TR alpha 1, alpha 1, beta 1 and beta 2 was performed. RA, T3 and DITPA significantly downregulated the alpha 1, beta 1 and beta 2. The T3 depleted medium did not affect the TR subtypes. The specificity of the solution hybridization method was tested by an RNase protection assay. In conclusion, RA downregulates TR in a similar way as T3 in cardiac cells, indicating a role for RA in thyroid associated heart disease.
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PMID:Downregulation of thyroid hormone receptor subtype mRNA levels by retinoic acid in cultured cardiomyocytes. 946 61

Recent studies have suggested that adrenomedullin (AM) may play a role in the pathophysiology of heart disease, though the specific cardiac receptors involved have not been defined. RT-PCR cloned fragments of three putative AM/calcitonin gene-related peptide (CGRP) receptors were used to established a quantitative RNase protection assay to identify and quantitate expression of receptor mRNAs in heart and in cardiac myocytes. Intact rat heart expressed mRNA encoding the putative AM/CGRP receptors RDC1 and CRLR at 37- and 15-fold higher levels, respectively, than the AM-selective receptor L1, with a qualitatively similar profile in cultured neonatal cardiac myocytes. The high level of expression of RDC1 and CRLR suggests that both AM and CGRP may have direct actions on the cardiac myocyte via common receptors that can interact with either ligand.
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PMID:Cardiac expression of genes encoding putative adrenomedullin/calcitonin gene-related peptide receptors. 978 7

Altered pulmonary vascular reactivity is a source of morbidity and mortality for children with congenital heart defects and increased pulmonary blood flow. Nitric oxide (NO) is an important mediator of pulmonary vascular reactivity. The objective of this study was to characterize potential early alterations in expression, localization, and activity of endothelial NO synthase (eNOS) induced by increased pulmonary blood flow and pulmonary hypertension. Utilizing aortopulmonary vascular graft placement in the fetal lamb, we have established a unique animal model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. Ten fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt). RNase protection assays and Western blotting were performed on lung tissue prepared from 4-wk-old shunt lambs and age-matched controls. eNOS mRNA (2.4:1, P < 0.05) and protein (2. 08:1, P < 0.05) were increased in lungs of shunt lambs. In situ hybridization and immunohistochemistry revealed that the increase was confined to the endothelium of pulmonary arteries. eNOS protein (1.55:1, P < 0.05) and tissue cGMP concentrations (2.1:1, P < 0.05) were also increased in isolated fifth-generation pulmonary arteries of shunt lambs. In addition, total lung eNOS activity was increased (2.9:1, P < 0.05). Thus we report a previously undescribed, early upregulation of eNOS gene expression and activity in lambs with increased pulmonary blood flow and pulmonary hypertension.
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PMID:Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension. 981 72

To determine whether a quantitative relationship exists between globin mRNAs and their translation product during stress erythropoiesis in infants with increased production of fetal hemoglobin (HbF), we measured and compared the relative amounts of the mRNAs of alpha-, beta-, and gamma-globins and their protein synthesis. The synthesis of globin in immature red cells was determined by the incorporation of [3H]leucine, followed by separation and quantification of the polypeptides by C4-reverse phase HPLC. The relative proportions of the mRNAs of the globins were determined by RNase protection assay. A comparison of blood samples from 17 infants expected to have increased production of HbF in relation to their developmental age (five infants of diabetic mothers, two infants with intrauterine growth retardation, one infant with bronchopulmonary dysplasia, and seven infants with cyanotic heart disease) revealed a very significant correlation (r2 = 0.994; p < 0.001) between the ratio of globin mRNAs encoding HbF ([gamma/(gamma + beta)] mRNAs) and the ratios of the de novo synthesis of HbF [gamma/(gamma + beta)]. When only the 10 infants who had increased HbF synthesis are included, the correlation remains unchanged (r2 = 0.997, p < 0.001). The data demonstrated that under conditions of erythropoietic stress, when HbF production is increased, there is a close relationship between the quantification of gamma-globin mRNA and gamma-globin synthesis. The usual methods of determining HbF synthesis can be replaced by globin mRNA determination, which can be performed rapidly with a minimal amount of blood.
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PMID:HbF synthesis during stress erythropoiesis as determined by gamma-mRNA/non-alpha-mRNA quantification. 1023 65

To characterize the role of the kallikrein-kinin system in diabetic cardiopathy, we studied the effect of streptozotocin (STZ) on the regulation of the myocardial bradykinin (BK) receptors, the B1 and B2 type, and two tissue kallikrein genes, rat kallikrein 1 (rKLK1) and rKLK7, in severely hyperglycemic rats. Experiments were performed in STZ-induced diabetic male Wistar rats (n = 7) and compared to controls (n = 7). After extraction of myocardial total RNA, specific oligonucleotides were used to generate reverse transcription PCR (RT-PCR) products from myocardial rKLK1 and rKLK7 mRNA. Southern blot analyses of these RT-PCR products were hybridized with appropriate gene-specific oligonucleotide probes. Myocardial B1 and B2 receptor expression were analyzed by RNase protection assays using specific probes from the coding region of the receptor genes. Twelve weeks after diabetes induction, the rats were normotensive and hyperglycemic and polyuric. We observed an impairment of the main myocardial kinin-forming enzymes, indicated by a reduction of the expression of both, rKLK1 and rKLK7. At this time the myocardial expression of the B1 receptor was not detectable in either group. Thus, the B1 receptor does not play a regulatory role in either the healthy or in STZ-diabetic heart. In contrast, the B2-receptor expression was detectable but did not differ significantly in either group. The reduced synthesis of myocardial tissue KLK implies a reduced capacity to generate BK in diabetic rats. This reduction is not compensated by elevated BK receptor levels. We suggest that alterations of the KKS may contribute to myocardial dysfunction in diabetes mellitus.
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PMID:Myocardial expression of rat bradykinin receptors and two tissue kallikrein genes in experimental diabetes. 1060 22

Plasma concentrations of endothelin-1 (ET-1) are increased in children with congenital heart disease associated with increased pulmonary blood flow. However, the role of ET-1 in the pathophysiology of pulmonary hypertension remains unclear. Preproendothelin-1 gene expression is increased in adults with advanced pulmonary hypertension. To characterize potential early molecular alterations in the ET-1 cascade induced by increased pulmonary blood flow and pulmonary hypertension, fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt). RNase protection assays and Western blot analysis were performed on lung tissue prepared from 4-wk-old shunt lambs and age-matched controls. Endothelin-converting enzyme-1 [the enzyme responsible for the production of active ET-1 from big ET-1, mRNA (411%, p<0.05)] and protein (170%, p<0.05) were increased in lung tissue prepared from shunt lambs, compared with age-matched controls. Endothelin type A receptor (the receptor that mediates vasoconstriction), mRNA (246%, p<0.05), and protein (176%, p<0.05) also were increased in lung tissue prepared from shunt lambs compared with age-matched controls. Conversely, endothelin type B receptor (the receptor that mediates vasodilation), mRNA (46%, p<0.05), and protein (65%, p<0.05) were decreased in shunt lambs. Both the mRNA and protein levels for preproendothelin-were unchanged. Thus we conclude that increased pulmonary blood flow and pulmonary hypertension induce early alterations in the ET-1 cascade that result in increased ET-1 production, increased ET-1-mediated vasoconstriction, and decreased vasodilation. These early alterations in gene expression may contribute to the development of pulmonary hypertension and its associated enhanced pulmonary vascular reactivity.
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PMID:Altered regulation of the ET-1 cascade in lambs with increased pulmonary blood flow and pulmonary hypertension. 1062 89