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Titolo:
Oxidized LDL regulates vascular endothelial growth factor expression in human macrophages and endothelial cells through activation of peroxisome proliferator-activated receptor-gamma
Autore:
Inoue, M; Itoh, H; Tanaka, T; Chun, TH; Doi, K; Fukunaga, Y; Sawada, N; Yamshita, J; Masatsugu, K; Saito, T; Sakaguchi, S; Sone, M; Yamahara, K; Yurugi, T; Nakao, K;
Indirizzi:
Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 Clin Sci, Sakyo Ku, Kyoto 6068507, Japan
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 4, volume: 21, anno: 2001,
pagine: 560 - 566
SICI:
1079-5642(200104)21:4<560:OLRVEG>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY LIPOPROTEINS; PERMEABILITY FACTOR; INSULIN-RESISTANCE; PPAR-GAMMA; ATHEROSCLEROTIC LESIONS; GENE-EXPRESSION; ADIPOGENESIS; THIAZOLIDINEDIONES; TROGLITAZONE; PROGRESSION;
Keywords:
vascular endothelial growth factors; atherosclerosis; macrophages; endothelial cells; peroxisome proliferator-activated receptor-gamma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Itoh, H Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan Kyoto Univ 54 Shogoin Kawahara Cho Kyoto Japan 6068507 507, Japan
Citazione:
M. Inoue et al., "Oxidized LDL regulates vascular endothelial growth factor expression in human macrophages and endothelial cells through activation of peroxisome proliferator-activated receptor-gamma", ART THROM V, 21(4), 2001, pp. 560-566

Abstract

Vascular endothelial growth factor (VEGF) has been recognized as an angiogenic factor that induces endothelial proliferation and vascular permeability. Recent studies have also suggested that VEGF can promote macrophage migration, which is critical for atherosclerosis. We have reported that VEGF isremarkably expressed in activated macrophages, endothelial cells, and smooth muscle cells within human coronary atherosclerotic lesions, and we have proposed the significance of VEGF in the progression of atherosclerosis. Toclarify the mechanism of VEGF expression in atherosclerotic lesions, we examined the regulation of VEGF expression by oxidized low density lipoprotein (Ox-LDL), which is abundant in atherosclerotic arterial walls. A recent report has revealed that peroxisome proliferator-activated receptor-gamma (PPAR gamma) is expressed not only in adipocytes but also in monocytes/macrophages and has suggested that PPAR gamma may have a role in the differentiation of monocytes/macrophages. Furthermore, 9- and 13-hydroxy-(S)-10,12-octadecadienoic acid (9- and 13-HODE, respectively), the components of Ox-LDL, may be PPAR gamma ligands. Therefore, we investigated the involvement of PPAR gamma in the regulation of VEGF by Ox-LDL. PPAR gamma expression was detected in human monocyte/macrophage cell lines, human acute monocytic leukemia (THP-1) cells, and human coronary artery endothelial cells (HCAECs). Ox-LDL (10 to 50 mug/mL) upregulated VEGF secretion from THP-1 dose-dependently. VEGF mRNA expression in HCAECs was also upregulated by Ox-LDL. The mRNA expression of VEGF in THP-1 cells and HCAECs was also augmented by PPAR gamma activators, troglitazone (TRO), and 15-deoxy-Delta (12,14)-prostaglandinJ(2) (PGJ2). In contrast, VEGF expression in another monocyte/macrophage cell line, human histiocytic lymphoma cells (U937), which lacks PPAR gamma expression, was not augmented by TRO or PGJ2. We established the U937 cell line, which permanently expresses PPAR gamma (U937T). TRO and Ox-LDL augmented VEGF expression in U937T. In addition, VEGF production by THP-1 cells was significantly increased by exposure to 9-HODE and 13-HODE. In conclusion,Ox-LDL upregulates VEGF expression in macrophages and endothelial cells, at least in part, through the activation of PPAR gamma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 05:45:15