Angiotensin-Converting Enzyme: Vascular Endothelial Localization

Caldwell, P. R. B.; Seegal, Beatrice Carrier; Hsu, Konrad C.; Das, Manjusri; Soffer, Richard L.

doi:10.1126/science.175444

Cited by 616 publications

(228 citation statements)

References 23 publications

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“…These findings do not bear out previous data indicating that the converting enzyme is mainly localized in vascular endothelium (Caldwell et al, 1976;Ryan et al, 1976). However, they are in good agreement with the results of more recent pharmacological and biochemical studies.…”

Section: Discussionsupporting

confidence: 69%

“…In particular, the endothelium of blood vessels has been shown to be a major site of conversion of AI to All by the converting enzyme located on its luminal surface (Caldwell et al, 1976;Ryan et al, 1976). Moreover, bovine aortic endothelial cells have been shown to contain renin and angiotensinogen and to be capable of synthesizing and secreting angiotensins (Lilly et al, 1985;Kifor & Dzau, 1987).…”

Section: Introductionmentioning

confidence: 99%

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Local formation of angiotensin II in the rat aorta: effect of endothelium

Eglème

Cressier

Wood

1990

British J Pharmacology

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1 The local formation of angiotensin II (All) from its precursors, angiotensin I (Al) and tetradecapeptide (TDP) renin substrate, was studied in intact (with endothelium) and rubbed (without endothelium) aortic rings of the rat. 2 AI and TDP renin substrate maximally contracted intact tissues in a similar way to All. The same observations were made in rubbed tissues. 3 The maximal response and the sensitivity of the aorta to these agonists were greater in rubbed than in intact tissues. 4 In intact preparations, methylene blue increased the contractile response to All and TDP to the same extent as endothelium removal. 5 In intact preparations, All receptor blockade completely suppressed all contractile responses, converting enzyme inhibition completely blocked the responses to AI and TDP, and renin inhibition partially blocked the responses to TDP. 6 In rubbed preparations, All receptor blockade completely inhibited all contractile responses, converting enzyme inhibition completely suppressed the responses to AI but only partially inhibited those to TDP, and renin inhibition partially blocked the responses to TDP. 7 In conclusion, the formation of All from TDP and its blockade by a converting enzyme inhibitor and a renin inhibitor shows that converting enzyme and a renin-like aspartic proteinase are present in the aortic wall. Furthermore, the results show that the endothelium is not essential for the conversion of the TDP to All, but modulates the responses to locally formed All through the release of endotheliumderived relaxing factor (EDRF).

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Local formation of angiotensin II in the rat aorta: effect of endothelium

Eglème

Cressier

Wood

1990

British J Pharmacology

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“…1 A and B). Their ultrastructure and the presence of certain biochemical markers [e.g., angiotensin-converting enzyme (17) The morphology and orientation of these cultures were changed dramatically in the presence of PMA, a tumor-promoting agent (18) (Fig. 1 C and D).…”

mentioning

confidence: 99%

“…2A). Although the relative fibrinolytic activity was low compared to that observed for transformed cells (12) [12][13][14][15][16][17][18][19][20][21][22][23][24] hr. Urokinase-mediated fibrinolysis was also sensitive to the inhibitor present in these extracts., Cell fractionation studies were performed to localize Pmg A and inhibitor to specific subcellular fractions.…”

mentioning

confidence: 99%

Synthesis of fibrinolytic activator and inhibitor by endothelial cells

Loskutoff

Edgington

1977

Proc. Natl. Acad. Sci. U.S.A.

394

139

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Vascular endothelial cells derived from rabbit vena cava and maintained in continuous culture exhibited properties characteristic of the intact endothelium. These cells were used as a model for characterizing the fibrinolytic components specified by the endothelium. Endothelial cells in culture digested radiolabeled fibrinogen. Digestion resulted from the synthesis and secretion of a plasminogen activator. Fibrinolysis was not detected when cells were grown in medium lacking plasminogen, indicating the absence of plasminogenindependent fibrinolytic enzymes. Phorbol-myristate-acetate increased extracellular plasminogen activator activity dramatically. This increase was prevented when actinomycin D or cycloheximide was included in the growth medium, indicating that new gene expression was required for it. Intracellular plasminogen activator could not be detected unless the cell extracts were exposed briefly to mildly acidic conditions. Mixing experiments between acid-treated and untreated extracts suggested that the cells contained a potent, acid-labile inhibitor of fibrinolysis. As little as 10 gg of protein from whole cell extracts inhibited both cell and urokinase-mediated fibrinolysis by more than 70%. Cell fractionation studies localized the inhibitor to the cytosol whereas plasminogen activator activity was restricted to the membrane-rich fraction. This membrane fraction did not require acidification for activity, suggesting that the inhibitor had been removed and that acidification did not activate a plasminogen proactivator. These observations demonstrate that regulation of endothelial fibrinolytic activity is far more complex than had been anticipated and raise several uncertainties in regard to detecting the presence of plasminogen activators in cells and tissues.

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“…[3][4][5][6] The unique tissue distribution of endothelial ACE, along with preferential expression in lung capillaries, 5,6 also makes it an almost ideal target for therapy directed toward pulmonary endothelium.…”

Section: Introductionmentioning

confidence: 99%