LETTER TO THE EDITOR
Paclitaxel-coated stent: is there a light at the end of the tunnel?
Nicholas Kipshidze, MD, PhDa,
Jeffrey W. Moses, MDa and
Martin B. Leon, MDa
a Lenox Hill Heart and Vascular Institute of New York, 130 East 77th Street Black Hall—9th Floor New York, New York 10021, USA
nkipshidze{at}lenoxhill.net
We read with great interest the study by Drachman et al.(1). Their study determines long-term effects of stent-based paclitaxel delivery and its influence on neointimal thickening in a rabbit injury model.
Their report highlights the importance of stents with drug delivery capabilities and therefore signals the beginning of the era of "smart" stents. An important question unanswered in their study is the gender bias in paclitaxel therapy. It is well established that the chemotherapeutic effect of paclitaxel is mediated through the plasma membrane estrogen receptors (2). It is also widely accepted that this is particularly effective in breast and ovarian neoplasms (3–5).
In contrast, the estrogen receptors in the human cells, including arterial smooth muscle cells (SMC), are probably less developed in the male cell system. Therefore, it will be extremely interesting to investigate the effect of paclitaxel-coated stents on myointimal hyperplasia in male and female animals.
Another issue of this antiproliferative approach for restenosis is the nonselective nature of this modality, which also includes suppression of endothelial cell growth. Although the Drachman et al. (1) study along with others demonstrates complete endothelialization of the coated stents at follow-up, histology is not always an absolute indicator of the endothelialization process. Many believe there is the phenomenon of pseudo-endothelialization. Synthetic or proliferative SMC that line the surface of the vessel after injury may perform many, but not all, functions of endothelial cells. Therefore, functional studies are necessary to address the issue of true endothelialization and, subsequently, late thrombosis.
Finally, the issue of modulation of collagen production by SMC needs to be addressed. The arrest of SMC migration and proliferation will not be enough to reverse the process of restenosis. It might be that paclitaxel therapy of the vessel wall also abolishes collagen production. Importantly, further in vitro and in vivo studies will help to understand antirestenotic properties of this compound.
Thus, additional experimental studies that will address all these issues might indeed allow us to see the beginning of the end of a long and difficult journey of restenosis prevention.
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References
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1. Drachman DE, Edelman ER, Seifert P, et al. Neointimal thickening after stent delivery of paclitaxel: change in composition and arrest of growth over six months. J Am Coll Cardiol. 2000;36:2325–2332[Abstract/Free Full Text]
2. Razandi M, Pedram A, Levin ER. Plasma membrane estrogen receptors signal to antiapoptosis in breast cancer. Mol Endocrinol. 2000;14:1434–1447[Abstract/Free Full Text]
3. Kuter I. Breast cancer update. Oncologist. 2000;5:285–292[Abstract/Free Full Text]
4. Lin HL, Liu TY, Chau GY, Lui WY, Chi CW. Comparison of 2-methoxyestradiol-induced, docetaxel-induced, and paclitaxel-induced apoptosis in hepatoma cells and its correlation with reactive oxygen species. Cancer. 2000;89:983–994[CrossRef][Medline]
5. Wang Z, Yang D, Mohanakrishnan AK, et al. Synthesis of B-ring homologated estradiol analogues that modulate tubulin polymerization and microtubule stability. J Med Chem. 2000;43:2419–2429[CrossRef][Medline]
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