doi: 10.1161/01.CIR.0000132468.82942.F5
(Circulation. 2004;109:2826-2831.)
© 2004 American Heart Association, Inc.
Reviews: Current Perspectives |
Janus Phenomenon
The Interrelated Tradeoffs Inherent in Therapies Designed to Enhance Collateral Formation and Those Designed to Inhibit Atherogenesis
From the Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC.
Correspondence to Stephen E. Epstein, MD, Cardiovascular Research Institute, Washington Hospital Center, 110 Irving St NW, 4B-1, Washington, DC 20010. E-mail stephen.epstein@medstar.net
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Enormous advances have occurred in the understanding of the molecular and cellular mechanisms responsible for both collateral development (collaterogenesis*) and atherogenesis. This advancement has been accompanied by parallel advances in therapies designed to enhance collaterals and to inhibit the development and progression of atherosclerosis. Our laboratory has been interested in both areas, and during our work, we noticed a consistent tradeoff: Whatever intervention enhanced collaterals increased atherogenesis and visa versa. We refer to this tradeoff as the Janus phenomenon.
This observation, if correct, is of more than passing interest given the many antiatherosclerotic interventions used in patients and the proangiogenic interventions being tested that may soon be used therapeutically. Therefore, if the Janus phenomenon is real, its clinical implications would be of critical importance. Equally as important, the concept might provide mechanistic insights into both atherogenesis and collaterogenesis.
Consequently, we began to track phenomena compatible with the Janus concept. Table 1 lists a few molecules for which reasonable evidence exists relating to both their atherosclerotic and collaterogenic effects and the actions of which are compatible with the Janus phenomenon.1–18 Complementary to the information contained in Table 1 are the opposite concordances displayed by different mouse strains regarding collaterogenic potential versus atherogenic susceptibility. C57BL/6 mice are susceptible to atherosclerosis and are exuberant collateral formers. Conversely, Balb/C mice are resistant to atherosclerosis and have an inferior collaterogenic capacity,19,20 suggesting that genetic determinants conveying susceptibility to atherogenesis will convey an enhanced capacity for collaterogenesis and visa versa. Therefore, the Janus phenomenon, expressing
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