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 purpose of this study was to develop an experimental model of neonatal right ventricular hypertrophy which was similar to human congenital heart disease associated with pulmonary hypertension. Monocrotaline (200 mg/kg), a pyrrolizidine alkaloid, was injected into neonatal Hartley guinea pigs on the day of delivery. The occurrence of pulmonary hypertension and right ventricular hypertrophy was confirmed by pressure studies and a determination of the right ventricular wet weight and myocyte diameter on the seventh day after delivery. Right ventricular systolic pressure was significantly increased at 7 days after monocrotaline treatment compared with the untreated control group. The ratio of right ventricular systolic pressure to left ventricular systolic pressure, an indicator of pulmonary hypertension, was significantly elevated from 0.32 +/- 0.02 in the controls to 0.59 +/- 0.03 in the monocrotaline group. Right ventricular wet weight was also significantly increased, indicating right ventricular hypertrophy. The diameter of cardiac myocytes was significantly increased in the right ventricle, and was decreased in the left ventricle and interventricular septum in the monocrotaline group. Neonatal guinea pigs developed pulmonary hypertension and marked right ventricular hypertrophy within 1 week after treatment with monocrotaline. This simple experimental model may have features similar to those of human congenital heart disease associated with pulmonary hypertension.
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PMID:Induction of right ventricular hypertrophy in neonatal guinea pigs by monocrotaline. 888 63

Pulmonary arterial hypertension (PAH) is a pulmonary angioproliferative disease with high morbidity and mortality, characterized by a typical pattern of pulmonary vascular remodeling including neointimal lesions. In congenital heart disease, increased pulmonary blood flow has appeared to be a key mediator in the development of these characteristic lesions, but the molecular mechanisms underlying the pulmonary vascular lesions are largely unknown. We employed a rat model of flow-associated PAH, which induced specific pulmonary neointimal lesions. We identified gene expression profiles in rats specifically related to the addition of increased pulmonary blood flow to monocrotaline and the associated occurrence of neointimal lesions. Increased pulmonary blood flow induced the expression of the transcription factors activating transcription factor-3 (ATF3) and early growth response factor-1 (EGR-1), for which presence was confirmed in neointimal lesions. Monocrotaline alone induced increased numbers of activated mast cells and their products. We further identified molecular pathways that may be involved in treatment with the prostacyclin analog iloprost, a vasoactive compound with clinically beneficial effects in patients with PAH, which were similar to pathways described in samples from patient studies. These pathways, associated with the development of angioproliferative lesions as well as with the response to therapy in PAH, may provide new therapeutic targets.
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PMID:Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions. 2002 77