Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potent vasoconstrictor peptide angiotensin II (ang II) has been shown to promote growth of vascular smooth muscle cells (VSMC) in vitro and in vivo. We have previously demonstrated that VSMC synthesize insulin-like growth factor I (IGF I), an important autocrine/paracrine growth factor. Exposure of quiescent VSMC to ang II caused a marked increase in IGF I mRNA levels, peaking at 6 h (199 +/- 26% above control) and sustained for at least 24 h. This increase was completely inhibited by actinomycin D. Nuclear run-on assays indicated that ang II stimulated IGF I gene transcription 3.6-fold. Protein synthesis inhibition with cycloheximide increased basal IGF I mRNA levels but blocked ang II-induced IGF I expression. Immunoreactive IGF I levels in VSMC-conditioned medium were increased by 2.7-fold 24 h following ang II exposure. Measurements of [3H]thymidine incorporation showed that ang II caused a 117% increase in DNA synthesis at 24 h that was almost completely inhibited in the presence of an anti-IGF I antibody. Thus, ang II regulates transcription of the IGF I gene in VSMC and IGF I is required for ang II-induced DNA synthesis. These findings suggest a potentially important role for IGF I as a mediator of the vascular growth responses induced by activation of the renin-angiotensin system in vivo.
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PMID:Angiotensin II regulates insulin-like growth factor I gene expression in vascular smooth muscle cells. 834 66

We have previously demonstrated specific insulin-like growth factor I (IGF I) mRNA transcripts in cultured endothelial and vascular smooth muscle cells and postulated an important role for IGF I in blood vessel growth responses. The purpose of this study was to characterize IGF I gene expression in a model of aortic coarctation hypertension in the rat. This high-renin model of hypertension is associated with hyperplastic vascular responses. Northern analysis of rat aorta demonstrated four specific IGF I mRNA transcripts sized 7.6, 4.6, 1.8, and 0.9-1.2 kb. Quantitation of aortic IGF I mRNA levels by solution hybridization/RNase protection assay demonstrated induction of IGF I transcripts in the hypertensive aorta; levels more than doubled at 7 days and were still significantly elevated 21 days after coarctation. In situ hybridization analysis indicated that IGF I transcripts were localized primarily to adventitial surfaces in normotensive aorta, with minimal signal detected over vascular cells. In hypertensive aortas, there was an increase in IGF I transcripts primarily over vascular smooth muscle cells. Thus, vascular IGF I gene expression is induced in this model of high-renin hypertension. IGF I may play an important role in autocrine/paracrine-mediated vessel wall remodeling in hypertension.
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PMID:Abdominal coarctation increases insulin-like growth factor I mRNA levels in rat aorta. 841 83

The renin-angiotensin system regulates normal cardiovascular homeostasis and is activated in certain forms of hypertension and in heart failure. Angiotensin II has multiple physiological effects and we have shown recently that its growth-promoting effects on vascular smooth muscle require autocrine activation of the IGF I receptor. To study the effect of angiotensin II on circulating IGF I, we infused rats with 500 ng/kg/min angiotensin II for up to 14 d. Angiotensin II markedly reduced plasma IGF I levels (56 and 41% decrease at 1 and 2 wk, respectively) and IGF binding protein-3 levels, and increased IGF binding protein-2 levels, a pattern suggestive of dietary restriction. Compared with sham, angiotensin II-infused hypertensive rats lost 18-26% of body weight by 1 wk, and pair-feeding experiments indicated that 74% of this loss was attributable to a reduction in food intake. The vasodilator hydralazine and the AT1 receptor antagonist losartan had comparable effects to reverse angiotensin II-induced hypertension, but only losartan blocked the changes in body weight and in circulating IGF I and its binding proteins produced by angiotensin II. Moreover, in Dahl rats that were hypertensive in response to a high-salt diet, none of these changes occurred. Thus, angiotensin II produces weight loss through a pressor-independent mechanism that includes a marked anorexigenic effect and an additional (likely metabolic) effect. These findings have profound implications for understanding the pathophysiology of conditions, such as congestive heart failure, in which the renin-angiotensin system is activated.
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PMID:Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism. 864 43

Moderately elevated maternal cortisol levels late in gestation cause enlargement of the fetal sheep heart. We have used quantitative real-time PCR to examine expression of candidate genes in fetal hearts from mothers in whom cortisol levels were increased (by infusion of 1 mg cortisol.kg(-1).day(-1)) or decreased (by adrenalectomy and replacement to 0.5 mg cortisol.kg(-1).day(-1)) from 115 to 130 days gestation. Control ewes were not treated with steroid. Expression of mineralocorticoid receptor (MR), glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenases 1 and 2 (11beta-HSD1 and -2), IGF I and II, IGF receptors 1 and 2 (IGF-1R and IGF-2R), endothelial nitric oxide synthase, VEGF, myotrophin, angiotensinogen, the angiotensin receptors 1 and 2 (AT1R and AT2R), and the angiotensin converting enzymes 1 and 2 were measured. MR mRNA abundance in fetal hearts was found to be similar to that in adult kidney and hippocampus. Although there were no significant changes in most genes, 11beta-HSD2 and IGF-1R expression were significantly decreased in the high cortisol group and 11beta-HSD2 expression negatively correlated to left ventricular wall thickness. There was also a significant change in the ratio of AT receptor expression, with increased AT2R and decreased AT1R in the high cortisol group. MR, GR, and 11beta-HSD1 immunoreactivity was found in cardiomyocytes and cardiac blood vessels in 126-128 day fetal sheep; in contrast 11beta-HSD2 staining was predominantly in blood vessels. These results indicate that cortisol could indeed act in the fetal heart to induce enlargement and suggest that the renin-angiotensin system may play a role.
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PMID:Increased maternal cortisol in late-gestation ewes decreases fetal cardiac expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA. 1690 87