Disease relevance of P-HYDROXYPHENOXYACETIC ACID

• RESULTS: Five of the 6 animals receiving an RG-13577/ATA-coated stent experienced acute stent thrombosis, while no adverse events occurred in the animals of the other 2 groups [1].
• In this study we clarify the mode of action of RG-13577 and demonstrate that the RG-13577-induced hypertrophy is associated with an increased expression of TGF-beta1 as indicated by an increase in TGF-beta1-specific protein and mRNA level [2].

High impact information on P-HYDROXYPHENOXYACETIC ACID

• RG-13577 inhibited FGF-2 binding to soluble- and cell surface-FGF receptor 1 (FGFR1) [3].
• METHODS AND RESULTS: Injured and noninjured saphenous vein segments were perfused with or without heparin, in the absence or presence of 125I-bFGF and/or RG-13577 (a polymer of 4-hydroxyphenoxy acetic acid) [4].
• In a search for a superior antiproliferative agent, a synthetic polyaromatic "heparin mimicking" compound (RG-13577, polymer of 4-hydroxyphenoxy acetic acid, M(r) approximately 5800), previously reported to inhibit the proliferation of vascular smooth muscle cells, was applied [5].
• RG-13577 binds to a naturally produced extracellular matrix, and the bound molecule retained its antiproliferative effect toward MC [5].
• Furthermore, the antiproliferative effect of RG-13577 was abolished in the presence of lactoferrin [5].

Chemical compound and disease context of P-HYDROXYPHENOXYACETIC ACID

• PURPOSE: To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA]) and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2 (bFGF2) could be combined as a stable compound and attached to conventional bare metal stents to hinder thrombus formation and inflammatory reactions of stenting [1].
• Paradoxical effects of aurintricarboxylic acid and RG-13577: acute thrombosis and in-stent stenosis in a passive-coated stent [1].

Biological context of P-HYDROXYPHENOXYACETIC ACID

• Unlike heparin, RG-13577 alone failed to mediate dimerization of FGF-2 [3].
• The RG-13577 effect is reversible since incubation of hypertrophic cells in RG-13577-free medium restores cell volume and [3H]thymidine incorporation to the values of untreated control cells within 4 days [2].
• We conclude, that the active metabolic status of RG-13577-treated cells in association with the overexpression of TGF-beta could promote repair processes of injured arteries after angioplasty without stimulating cell proliferation [2].

Anatomical context of P-HYDROXYPHENOXYACETIC ACID

• FGF-2-stimulated proliferation of vascular endothelial cells was markedly inhibited in the presence of 5-10 microg/ml compound RG-13577 (poly-4-hydroxyphenoxy acetic acid; Mr approximately 5 kD) [3].
• METHODS: Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA-coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD) and left circumflex (LCX) coronary arteries [1].
• RG-13577, delivered intraperitoneally, inhibited the clinical signs of acute EAE and markedly ameliorated inflammation in the spinal cord, primarily by inhibiting heparanase activity in lymphocytes and astrocytes and thus impairing lymphocyte traffic [6].

Gene context of P-HYDROXYPHENOXYACETIC ACID

• One has here investigated the effects of RG-13577 on LPL, both after intravenous injection to rats and under cell culture conditions [7].
• These results indicate that RG-13577 and related compounds bind to the LRP receptor on the surface of vascular SMCs [8].
• There was a slight increase in TF staining around the stent struts, while SEM showed increased platelet adhesion and activity in RG-13577/ATA-coated stents versus the ATA-coated and bare metal stents [1].

Analytical, diagnostic and therapeutic context of P-HYDROXYPHENOXYACETIC ACID

• CONCLUSION: RG-13577/ATA-coated stents lead to acute stent thrombosis [1].
• Finally, the ability of reverse thermo-sensitive gels to perform as drug delivery systems was exemplified by releasing an anti-restenosis model drug (RG-13577) [9].

References