WHG, Peter Suzman, and anyone else interested in VEGF gene therapy--
In a recent issue of the journal Circulation (1999;99:3043; text can be obtained via the American Heart Association website under "Scientific Publications", then "Circulation"; I believe it is the June 15 edition), Isner's group reports that in a rabbit hind limb ischemia model, the ACE inhibitor quinaprilat (an oral agent) was as effective as recombinant human VEGF in producing angiogenesis. They conclude:
"The results of the present study establish that ACE inhibition with quinaprilat promotes angiogenesis in the rabbit ischemic hindlimb to the same extent as rhVEGF." (pp 3045)
Interestingly, another ACE inhibitor, captopril, showed no effect on angiogenesis compared to controls.
The authors speculated that the mechanism of quinaprilat-induced angiogenesis is indirect, proceeeding via increased endothelial cell nitric oxide synthesis. They further suggested that the effects of rhVEGF and quinaprilat may be synergistic, although they offered no supporting evidence. No doubt, they are busy testing this hypothesis at the moment. The authors also suggested that the efficacy of ACE inhibitor therapy in treating CHF and, particularly ischemic cardiomyopathies, may be mediated by the angiogenesis-promoting effects of ACE inhibition in the myocardium.
The implications of this study are evident: if one can achieve, via a common, relatively inexpensive oral agent the same clinical benefit that VEGF gene therapeutic approaches hope to provide, then the commercial potential of VEGF gene therapy becomes virtually nonexistent, at least for that purpose. I'm sure this potential application is not lost on the manufacturers of the various ACE inhibitors, also. Presently, to the best of my knowledge, they are not prescribed for peripheral vascular disease (an entity that VEGF gene therapy would potentially target), but if clinical data showed a benefit with ACE inhibition, then VEGF would have significant, and perhaps insurmountable competition.
Something to consider.
Regards,
Walkingshadow |
