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Current Topics in Biochemical Research   Volumes    Volume 3 
Caveolae, caveolar enzymes and angiogenesis
Vittorio Tomasi, Enzo Spisni, Cristiana Griffoni, Tiziana Guarnieri
Pages: 81 - 90
Number of pages: 10
Current Topics in Biochemical Research
Volume 3 

Copyright © 2000 Research Trends. All rights reserved


Studies on the formation and function of caveolae are likely to accelerate not only the understanding of intracellular events mechanisms as transcytosis, but to throw more light on the several steps required by endothelial cells to construct new capillaries, to adapt the function of an organ to a decrease in perfusion pressure or to hypoxia. The induction of vascular remodeling is the target of many attempts directed towards the therapy of often fatal diseases as systemic and pulmonary hypertension and cardiac ischemia The discovery of VEGF as a potent angiogenic stimulus, has promoted several studies aimed at using VEGF isoforms and/or gene therapy based on the use of the gene to induce compensatory angiogenesis. So far results are disappointing and the well known propensity of tumors to use VEGF to induce neovascularisation are not encouraging further trials. An interesting alternative to VEGF is represented by prostacyclin (PGI2) stable analogues, which have been proved to be very effective in the treatment of pulmonary hypertension. We will review the evidence that PGI2 in vitro and in vivo behaves as an inducer of angiogenesis. The enzyme forming PGI2 is strategically located in caveolae and since caveolae are involved in vascular remodeling, our conclusion is that PGI2 is likely to participate to crucial phases of angiogenesis and that stable analogues may be useful to induce angiogenesis not only in pulmonary hypertension, but also in systemic hypertension and in myocardial ischemia. On the other hand, inhibitors of angiogenesis have been proposed in the therapy of tumors. We have developed an antisense oligonucleotide strategy directed against caveolin-1 and active in vivo which we are testing against murine tumors.

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