Characteristics of Monocyte Angiotensin-Converting Enzyme (ACE) Induction by Dexamethasone

Vuk-Pavlović, Zvezdana; Kreofsky, Teresa J.; Rohrbach, Michael S.

doi:10.1002/jlb.45.6.503

Cited by 20 publications

(15 citation statements)

References 34 publications

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“…344 Our immunohistochemical data suggest that the cells containing ACE are primarily smooth muscle-like cells, as identified by positive costaining with a smooth muscle actin antibody. Although monocytes are known to express ACE (30,31 ), our immunostaining data demonstrated that only a few cells in the rat neointima stained positive for the macrophage marker, ED-1, and therefore cannot account for the robust ACE immunoreactivity in many cells in the lesion. The regenerated endothelial cells could be considered as another source ofACE after injury, since we noted positive immunohistochemical staining with vWF on the luminal layer of the neointima.…”

Section: Discussionmentioning

confidence: 65%

Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis.

Rakugi

Kim²,

Krieger³

et al. 1994

J. Clin. Invest.

231

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Angiotensin II (Ang II) promotes growth of vascular smooth muscle cells in vitro. Consistent with this, Ang II enhances neointimal proliferation in vivo after vascular injury, while angiotensin converting enzyme (ACE) inhibitors attenuate this process. Since tissue ACE plays a key role in the control of local Ang II production, we examined whether vascular injury resulted in an increase in vascular ACE expression that may result in increased Ang II production. Abdominal aorta of Sprague-Dawley rats were injured with a 2 French balloon catheter. Morphometrical changes, ACE enzymatic activity, and localization of ACE by immunohistochemistry in injured and uninjured aorta were analyzed. Vascular ACE activity in the injured aorta was significantly higher than in the uninjured aorta, while serum and lung ACE levels were not different between the two groups. The cellular distribution of the ACE protein in the neointima was similar to that of alpha smooth muscle actin but differed from those of endothelial (von Willebrand factor) or monocytes/macrophages (ED-1) markers, demonstrating that ACE was expressed in neointimal smooth muscle cells. These data demonstrate that vascular injury results in the induction of vascular ACE and suggest that the inhibition of vascular ACE may be important in the prevention of restenosis after balloon injury. (J. Clin. Invest. 1994. 339-346.)

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Section: Discussionmentioning

confidence: 65%

Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis.

Rakugi

Kim²,

Krieger³

et al. 1994

J. Clin. Invest.

231

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“…This hypothesis is based on previous studies in cultured cells: glucocorticoids induce an increase in NEP gene expression and in NEP activity in cultured human airway epithelial cells (10). Similarly, glucocorticoids induce ACE activity in cultures ofrabbit alveolar macrophages (1 1), bovine endothelial cells (12), and human monocytes (32). Pretreatment with dexamethasone results in an increase of ACE activity in homogenates of rat lungs (12).…”

Section: Discussionmentioning

confidence: 95%

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

Piedimonte¹,

McDonald²,

Nadel³

1991

J. Clin. Invest.

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Glucocorticoids inhibit plasma extravasation induced in the rat tracheal mucosa by substance P and other tachykinins released from sensory nerves. This study was performed to determine whether this antiinflammatory effect of glucocorticoids is mediated by the tachykinin-degrading enzymes neutral endopeptidase (NEP) and kininase II (angiotensin converting enzyme, ACE). In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE. Adult male pathogen-free F344 rats were treated for 2 d with dexamethasone (0.5 mg/kg per d i.p.), or with the vehicle used to dissolve the steroid. The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 Mg/kg) or PAF (10 ,Mg/kg) was then assessed by using Monastral blue pigment as an intravascular tracer. The role of NEP and ACE activities in the changes produced by dexamethasone was investigated by examining the effect of the selective inhibitors of these enzymes, phosphoramidon and captopril. Dexamethasone reduced the substance P-induced extravasation by 57% but did not affect the PAF-induced extravasation. The suppressive effect of dexamethasone on substance P-induced extravasation was completely reversed by simultaneously inhibiting NEP and ACE activities, but the inhibition of these enzymes had no effect on PAF-induced extravasation, regardless of whether the rats were pretreated with dexamethasone or not. These results suggest that NEP and ACE mediate a selective inhibitory effect of glucocorticoids on neurogenic plasma extravasation. (J.

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“…To measure the contributions of plasma-membrane-bound ACE and intracellular ACE to total cellular ACE activity, we used the diazonium salt of sulfanilic acid (DASA), an agent that does not penetrate plasma membrane of intact cells (3) and inhibits the activity of various ectoenzymes, including ACE (36). HUVEC were incubated with DASA (Fluka Chemica, Buchs, Switzerland) dissolved in KRB-HEPES, pH 7.4, at a final concentration of 10 -3-10 s M for 30 min at 37 ° C. After washing four times, ACE activity in intact cells and in cell lysates was measured as described above.…”

Section: Methodsmentioning

confidence: 99%

Modulation of angiotensin-converting enzyme in cultured human vascular endothelial cells

Balyasnikova

Danilov

Muzykantov

et al. 1998

In Vitro Cell.Dev.Biol.-Animal

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Previous work has suggested that not all immunoreactive angiotensin-converting enzyme (ACE) in tissues or cells is in a biologically active state. We have explored this possibility in cultured human umbilical vein endothelial cells (HUVEC), one of the most widely studied in vitro endothelial cell systems. Our approach included characterization of the effect of increasing passage number on ACE activity and expression of immunoreactive ACE at the single cell level, the subcellular compartmentalization of active ACE, and the effect of phorbol ester (PMA) treatment. We found that both ACE activity and expression of ACE antigen were downregulated by cultivation (30% of ACE-positive cells at seventh passage vs. 90% in primary culture). ACE downregulation is specific (number of CD31-positive cells did not change with cultivation) and correlated with downregulation of factor VIII-antigen. The percentage of ACE-positive cells in permeabilized HUVEC at third passage was almost twice that in nonpermeabilized HUVEC (90% vs. 50%), indicating that HUVEC contain intracellular immunoreactive ACE. ACE activity, however, was similar when measured in intact cells and in cell lysates. Moreover, diazonium salt of sulfanilic acid (DASA), a membrane-impermeable ACE inhibitor, inhibited ACE activity in intact cells and in cell lysates at the same extent, thus implying that intracellular ACE is inactive. PMA (100 nM) treatment increased the percentage of ACE-positive cells at third passage from 57 to 96%. ACE activity was increased 3-fold in cell and 1.5-fold in the culture medium of PMA-treated cells. Analysis of ACE activity in intact monolayers and cell lysates of control and PMA-treated cells revealed that all enzymatically active ACE in PMA-treated cells is localized on the plasma membrane and acts as an ectoenzyme. We conclude that expression of ACE by HUVEC is downregulated by repeated passage in culture but can be restored by PMA treatment. In addition, ACE expression is heterogeneous between neighboring cells, and total immunoreactive ACE protein associated with HUVEC includes an inactive pool of the enzyme.

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Characteristics of Monocyte Angiotensin-Converting Enzyme (ACE) Induction by Dexamethasone

Cited by 20 publications

References 34 publications

Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis.

Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis.

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

Modulation of angiotensin-converting enzyme in cultured human vascular endothelial cells

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