Sitosterol-stimulative production of plasminogen activator in cultured endothelial cells from bovine carotid artery

Hagiwara, Hiromi; Shimonaka, Motoyuki; Morisaki, Masuo; Ikekawa, Nobuo; Inada, Yuji

doi:10.1016/0049-3848(84)90075-6

Cited by 55 publications

(21 citation statements)

References 19 publications

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“…Cell Culture and Bioassay-Bovine carotid artery endothelial (BCAE) cells were isolated from adult bovine carotid arteries and cultured by the reported method (24,25). Briefly, fresh bovine carotid arteries were opened lengthwise with a scalpel.…”

Section: Methodsmentioning

confidence: 99%

Identification of Chondromodulin I as a Novel Endothelial Cell Growth Inhibitor

Hiraki¹,

Inoue²,

Iyama³

et al. 1997

Journal of Biological Chemistry

170

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Cartilage is unique among tissues of mesenchymal origin in that it is resistant to vascular invasion due to an intrinsic angiogenic inhibitor. During endochondral bone formation, however, calcified cartilage formed in the center of the cartilaginous bone rudiment allows vascular invasion, which initiates the replacement of cartilage by bone. The transition of cartilage from the angioresistant to the angiogenic status thus plays a key role in bone formation. However, the molecular basis of this phenotypic transition of cartilage has been obscure. We report here purification of an endothelial cell growth inhibitor from a guanidine extract of bovine epiphyseal cartilage. The N-terminal amino acid sequence indicated that the inhibitor was identical to chondromodulin I (ChM-I), a cartilage-specific growthmodulating factor. Purified ChM-I inhibited DNA synthesis and proliferation of vascular endothelial cells as well as tube morphogenesis in vitro. Expression of ChM-I cDNA in COS7 cells indicated that mature ChM-I molecules were secreted from the cells after post-translational modifications and cleavage from the transmembrane precursor at the predicted processing signal. Recombinant ChM-I stimulated DNA synthesis and proteoglycan synthesis of cultured growth plate chondrocytes, but inhibited tube morphogenesis of endothelial cells. In situ hybridization and immunohistochemical studies indicated that ChM-I is specifically expressed in the avascular zone of cartilage in developing bone, but not present in calcifying cartilage. These results suggest a regulatory role of ChM-I in vascular invasion during endochondral bone formation.

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Section: Methodsmentioning

confidence: 99%

Identification of Chondromodulin I as a Novel Endothelial Cell Growth Inhibitor

Hiraki¹,

Inoue²,

Iyama³

et al. 1997

Journal of Biological Chemistry

170

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“…EC were isolated from adult bovine carotid artery by scraping the intimal surface with a scalpel and cultured in DME (Flow Laboratories, Irvine, Ayrshire, Scotland) supplemented with 10% FCS (Hazleton Biologics, Inc., Lenexa, KS) at 370C in a humidified atmosphere containing 5% CO2 (22). Cells at passages 20-25 were used in the present study.…”

Section: Methodsmentioning

confidence: 99%

Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-beta. Possible existence of "vascular natriuretic peptide system".

Suga¹,

Nakao²,

Itoh³

et al. 1992

J. Clin. Invest.

496

255

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C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is thus far known to be distributed mainly in the central nervous system and is considered to act as a neuropeptide, in contrast to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which act as cardiac hormones. Recently, we and others have demonstrated that the ANP-B receptor, which is selectively activated by CNP, is localized not only in the central nervous system but in peripheral tissues, including blood vessels. This finding has made us speculate regarding the peripheral production of CNP. In the present study, cultured endothelial cells were examined for CNP production by RIA and Northern blot analysis. CNP-like immunoreactivity was detected in the conditioned media of endothelial cells. Northern blot analysis detected CNPmRNA with a size of 1.2 kb. In addition, transforming growth factor (TGF)-,8, one of the key growth factors for vascular remodeling, markedly stimulated the expression of CNPmRNA and induced a tremendous increase in CNP secretion. We could also detect CNP transcript in the bovine thoracic aorta using the reverse transcription-polymerase chain reaction method.The present study demonstrates the endothelial production of CNP and suggests that a member of the natriuretic peptide family may act as a local regulator in vascular walls. Since evidence for the pathophysiological importance of the vascular renin-angiotensin system has been accumulating and the natriuretic peptide system is known to be antagonistic to the reninangiotensin system, the possible existence of "vascular natriuretic peptide system" may prove to be of physiological and clinical relevance. (J. Clin. Invest. 1992. 90:1145-1149

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“…Two plant steroids, sitosterol and fucosterol, have been reported to induce a 3-to 7-fold increase in the production of PA activ ity in bovine carotid artery endothelial cells [101,118,119]. Fibrin autography after SDS-PAGE of the endothelial cell condi tioned medium showed that the production of both t-PA and u-PA was increased [101].…”

Section: Induction O F Newly Synthesized Pas By Cultured Endothelial mentioning

confidence: 99%

Regulation of the Synthesis and Secretion of Plasminogen Activators by Endothelial Cells

Hinsbergh¹

1988

Pathophysiol Haemos Thromb

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Plasminogen activators (PAs) play a role in fibrinolysis, tissue remodelling, tumor invasion, and reparative processes. Vascular endothelial cells produce tissue-type PA (t-PA), an important regulator of fibrinolysis, and PA inhibitor 1. They can also synthesize a second type of PA, urokinase-type PA (u-PA). The regulation of synthesis and secretion of these PAs by human and bovine endothelial cells in vitro is reviewed. The synthesis of t-PA and u-PA varies between endothelial cells, depending on their vascular origin. The production of PA activity by endothelial cells is regulated at various levels: (1) induction of newly synthesized t-PA or u-PA molecules; (2) rapid release of t-PA from endothelial cells; (3) conversion of single-chain u-PA in the more active two-chain u-PA; (4) interaction of PAs with cellular receptors and matrix components, and (5) interaction of PAs with specific inhibitors.

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Sitosterol-stimulative production of plasminogen activator in cultured endothelial cells from bovine carotid artery

Cited by 55 publications

References 19 publications

Identification of Chondromodulin I as a Novel Endothelial Cell Growth Inhibitor

Identification of Chondromodulin I as a Novel Endothelial Cell Growth Inhibitor

Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-beta. Possible existence of "vascular natriuretic peptide system".

Regulation of the Synthesis and Secretion of Plasminogen Activators by Endothelial Cells

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