In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 5 ( 1999-11), p. 1141-1146
Abstract:
Abstract —We have previously shown, in a neonatal rat cell line, that angiotensin II (Ang II)–induced proliferation in vascular smooth muscle cells is extracellular matrix (ECM) dependent. We hypothesized that such an effect might be mediated via differences in Ang II–induced increases in the transcriptional factor early growth response-1 (Egr-1) gene and, consequently, in platelet-derived growth factor (PDGF). Cultured human newborn aortic smooth muscle cells were studied on 4 different surfaces: (1) plastic, (2) laminin, (3) collagen, and (4) fibronectin. Ang II–induced increases in DNA synthesis were significantly greater on collagen (2.0±0.3-fold) and fibronectin (1.9±0.3-fold) than on laminin (1.0±0.2-fold) or plastic (1.4±0.2-fold). As with DNA synthesis, at 48 and 72 hours, Ang II–induced increases in cell numbers occurred only in cells grown on collagen and fibronectin culture plates and were blocked by an antagonist to the angiotensin type 1 (losartan, 10 μmol/L) but not the angiotensin type 2 (PD 123319, 10 μmol/L) receptor. Anti-PDGF AA antibody (6 μg/mL) blocked the increase in DNA synthesis by 60% to 64% in cells on collagen or fibronectin cultures but not on plastic cultures. When PDGF-AA (10 ng/mL) and Ang II were added together, DNA synthesis increased 2-fold and did not differ on the various ECM proteins. Increases in PDGF A-chain mRNA were observed only in cells grown on collagen (3.21±0.65-fold) and fibronectin (2.86±0.49-fold) plates 2 to 8 hours after the addition of Ang II and were blocked by losartan but not PD 123319. Expression of Egr-1, an early growth response gene, increased at 15 minutes, peaked at 30 minutes, and returned to normal after 2 hours with Ang II treatment. Ang II–induced increases in Egr-1 mRNA were greater on collagen (4.82±0.66-fold at maximum) and fibronectin (4.01±0.56-fold) than on laminin (2.74±0.45-fold) or plastic (2.53±0.40-fold) and were blocked by losartan but not PD 123319. Thus, in human vascular smooth muscle cells in culture, Ang II–induced proliferation is mediated via the angiotensin type 1 receptor, dependent on ECM proteins, and regulated by differential gene expression of Egr-1 and PDGF-1.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.34.5.1141
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1999
detail.hit.zdb_id:
2094210-2
Permalink