Induction by fibroblast growth factor of angiotensin converting enzyme in vascular endothelial cells invitro

Okabe, Tetsuro; Yamagata, Kazuo; Fujisawa, Michio; Takaku, Fumimaro; Hidaka, Hiroshi; Umezawa, Yu

doi:10.1016/0006-291x(87)91566-x

Cited by 24 publications

(19 citation statements)

References 8 publications

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“…30 Other investigators have demonstrated that fibroblast growth factor, known to stimulate the growth of vascular endothelial cells, could induce ACE activity in these cells. 31 These findings suggest that various growth factors or vasoactive agents may be involved in the hypertensioninduced ACE gene expression in the vascular wall.…”

Section: N8mentioning

confidence: 95%

Increase of angiotensin converting enzyme gene expression in the hypertensive aorta.

1992

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To investigate the possible role of vascular angiotensin converting enzyme (ACE) in the development and maintenance of hypertension, we examined aortic ACE messenger RNA (mRNA) levels in two-kidney, one clip (2K1C) hypertensive rats. The blood pressure was increased remarkably at 4 weeks (early stage) after clipping and remained elevated at 12 weeks (chronic stage). The aorta ACE mRNA levels were significantly elevated in both early and chronic stages concurrently with the increases in aortic ACE activity and blood pressure. The plasma renin activity rose markedly at 4 weeks, but returned to the normal level at 12 weeks. Neither ACE activity in the lung and plasma, nor ACE mRNA level in the lung was altered at either stage. The aorta and liver angiotensinogen mRNA levels and renal renin mRNA level were increased at 4 weeks but decreased at 12 weeks. These results indicate that the acceleration of all components in the renin-angiotensin system may contribute to the development of 2K1C hypertension in the early stage. In the chronic stage, the increased vascular ACE induced by the elevated ACE mRNA levels in the aorta may play the primary role in the acceleration of local angiotensin II formation and thus may sustain the hypertension. 2 little has been clarified for its pathophysiological significance. In particular, little attention has been focused on the pathophysiological roles of vascular angiotensin converting enzyme (ACE). The lack of interest may be due to the fact that the ACE is distributed in abundance throughout vascular systems, and this makes it a quite unlikely candidate for regulating the blood pressure. We previously have proposed the relevance of the vascular ACE to the pathogenesis of hypertension; these studies used various types of hypertensive models: two-kidney, one clip (2K1C) rats 34 and dogs 5 -6 ; onekidney, one clip (1K1C) rats 7 ; and spontaneously hypertensive rats (SHR). 8 In the chronic hypertensive stages of these models, the circulating RAS was unlikely to be responsible for the maintenance of high blood pressure because the plasma renin activity (PRA) and plasma ACE activity were not high. In contrast, the vascular ACE activity was consistently high irrespective of the different pathogenic backgrounds. This may imply that the increased ACE in the vascular tissues sustains the hypertension via an enhanced generation of angiotensin

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Section: N8mentioning

confidence: 95%

Increase of angiotensin converting enzyme gene expression in the hypertensive aorta.

1992

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“…The deletion allele of the insertion/deletion marker of the ACE gene was shown to be associated with an increased risk for myocardial infarction, left ventricular hypertrophy, vascular wall thickness, or vascular complications of diabetes (20). Results of these studies are not all concordant as can be expected from the modest relative risk increase that was found to be associated with the ACE genotype.In various conditions, such as diabetes, platelet-activating factor, or basic fibroblast growth factor stimulation, an increase in ACE activity has been reported in vivo or in vitro in vascular smooth muscle cells and EC (11,(21)(22)(23)(24). In these same experimental conditions, activation of PKC has also been reported in these cells (25)(26)(27).…”

mentioning

confidence: 89%

“…In various conditions, such as diabetes, platelet-activating factor, or basic fibroblast growth factor stimulation, an increase in ACE activity has been reported in vivo or in vitro in vascular smooth muscle cells and EC (11,(21)(22)(23)(24). In these same experimental conditions, activation of PKC has also been reported in these cells (25)(26)(27).…”

mentioning

confidence: 89%

Induction of Angiotensin I-converting Enzyme Transcription by a Protein Kinase C-dependent Mechanism in Human Endothelial Cells

Villard

Alonso

Agrapart

et al. 1998

Journal of Biological Chemistry

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Angiotensin I-converting enzyme (ACE) has been implicated in various cardiovascular diseases; however, little is known about the ACE gene regulation in endothelial cells. We have investigated the effect of the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) on ACE activity and gene expression in human umbilical vein endothelial cells (HUVEC). Our results showed a 3-and 5-fold increase in ACE activity in the medium and in the cells, respectively, after 24-h stimulation by PMA. We also observed an increase in the cellular ACE mRNA content starting after 6 h and reaching a 10-fold increase at 24 h in response to 100 ng/ml PMA as measured by ribonuclease protection assay. This effect was mediated by an increased transcription of the ACE gene as demonstrated by nuclear run-on experiments and nearly abolished by the specific PKC inhibitor GF 109203X. Our results indicate that PMA-activated PKC strongly increases ACE mRNA level and ACE gene transcription in HUVEC, an effect associated with an increased ACE secretion. A role for early growth response factor-1 (Egr-1) as a factor regulating ACE gene expression is suggested by both the presence of an Egr-1-responsive element in the proximal portion of the ACE promoter and the kinetics of the Egr-1 mRNA increase in HUVEC treated with PMA.Angiotensin I-converting enzyme (ACE) 1 is a dipeptidyl carboxypeptidase that generates the vasoconstrictor peptide and growth factor angiotensin II from angiotensin I and inactivates the vasodilator peptide bradykinin (1). ACE also cleaves other peptides such as substance P, enkephalins, neurotensin, and gonadotropin-releasing hormone, but these activities are of unknown physiological relevance (1).ACE is a membrane-bound enzyme located mainly at the luminal face of endothelial cells (EC) in blood vessels (2). In the plasma, ACE is present as a soluble form originating mainly from EC by a proteolytic cleavage (3).The level of ACE is stable in human plasma, and limited data are available on its regulation at the cellular or tissue level (4). In bovine aortic endothelial cells, ACE was shown to be increased slightly by glucocorticoids, density growth arrest, and ACE inhibitors (5-8). Glucocorticoids also induce ACE expression and activity in macrophages and rat vascular smooth muscle cells (9,10). In the latter cells, the induction is synergistic with basic fibroblast growth factor (11). ACE induction is also observed in several pathological processes. After balloon injury in rat arteries, ACE is induced in vascular neointimal cells, and ACE inhibition has a beneficial effect on neointimal proliferation in this experimental model, decreasing the neointima/media ratio (12). ACE was shown to be induced in the aortic wall in different models of rat hypertension such as renovascular hypertension (13) or hypertension induced by chronic administration of the nitric oxide synthesis inhibitor N -nitro-L-arginine-methyl ester (14). ACE expression is also increased in interstitial cells of the heart during renovascular hypertension...

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“…ACE is induced by vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells (HUVEC) (Okabe et al, 1987;Saijonmaa et al, 2001b) or downregulated by TNF-a and interleukin (IL)1b in HUVECs (Saijonmaa et al, 2001a). TNF-a stimulates TACE expression in murine and human endothelial cell lines (Bzowska et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of tumor necrosis factor-α-converting enzyme and angiotensin-converting enzyme by type I and II interferons in human normal and leukemic myeloid cells

et al. 2006

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The transmembrane metalloproteases angiotensin-converting enzyme (ACE) and tumor necrosis factor-a (TNF-a)-converting enzyme (TACE/ADAM-17) have been associated with inflammation, cancer progression and angiogenesis. Few investigations into the regulation of these enzymes by physiological stimuli have been reported. In this study, we investigated the influence of interferons (IFNs) type I (a, b) and II (c) on ACE and TACE expression of human leukemic NB4 cells and monocytes.We assessed the expression of proteases by reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence analyses. IFNc, but not type I IFNs, upregulated membrane ACE in a dose-and time-dependency and this was reflected by the increase of ACE enzymatic activity and ACE mRNA. ACE upregulation was dependent on protein synthesis. Treatment of the interferon responsive factor 1 (IRF1)-unresponsive HepG2 cell line with IFNc did not affect ACE expression, thus suggesting the participation of the IRF1 signaling pathway in IFNc-mediated ACE upregulation in myeloid cells. In contrast, both types of IFNs, in a dose-and time-dependent manner, downregulated surface TACE without affecting TACE transcript. Soluble TACE was not detected in the medium of IFN-treated cells. IFNc-mediated decrease of surface TACE in NB4 cells was reversible, and correlated with an increase in intracellular TACE, suggesting that cell surface TACE was internalized in response to IFNs. These findings, showing the presence of IFN-dependent controlled mechanisms by which ACE and TACE levels are regulated in human normal and leukemic myeloid cells, may have implications in the context of current investigations on the therapeutic potential of IFNs.

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Induction by fibroblast growth factor of angiotensin converting enzyme in vascular endothelial cells invitro

Cited by 24 publications

References 8 publications

Increase of angiotensin converting enzyme gene expression in the hypertensive aorta.

Increase of angiotensin converting enzyme gene expression in the hypertensive aorta.

Induction of Angiotensin I-converting Enzyme Transcription by a Protein Kinase C-dependent Mechanism in Human Endothelial Cells

Differential regulation of tumor necrosis factor-α-converting enzyme and angiotensin-converting enzyme by type I and II interferons in human normal and leukemic myeloid cells

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