Nicotine promotes arteriogenesis
Christopher Heeschen, MD* ,
Michael Weis, MD* and
John P. Cooke, MD, PhD, FACC*,*
* Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA
Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany
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Figure 1 Initial dose-escalating studies with nicotine concentrations ranging from 0.05 to 5.0 µg/kg/day with regional perfusion of the ischemic limb as determined by microsphere distribution as the primary end point. The nicotine concentrations of 5.0 µg/kg/day showed the strongest angiogenic response as compared with control.
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Figure 2 Selective internal iliac angiography at day 21-day in (A) control-, (B and C) nicotine-, and (D) basic fibroblast growth factor (bFGF)-treated rabbits. Nicotine was as potent as bFGF in stimulating arteriogenesis, although we observed more biologic variability in the response to nicotine. The two angiograms illustrate the range of response to nicotine.
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Figure 3 Nicotine or basic fibroblast growth factor (bFGF) treatment enhance revascularization. (A) Angiographic score at day 0 (immediately postoperation; open bars) and day 21 after treatment (closed bars). (B) Capillary density (capillaries/myocyte) at day 21. (C) Number of collateral vessels per cross-section as determined by light microscopy. (D) Microsphere distribution in the gastrocnemius muscles. (E) Relative Doppler-derived flow in the internal iliac artery of the ischemic limb at rest (open bars) and hyperemia after adenosine infusion (closed bars) at day 21. Relative to the contralateral, nonischemic limb, maximum flow in the internal iliac artery of the ischemic limb increased in the nicotine group by 4.1-fold, in the bFGF group by 3.3-fold, and in the control by 2.0-fold. *p < 0.01 with one-way analysis of variance.
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Figure 4 (A) Flow cytometry revealed that nicotine stimulated the expression of CD11b on peripheral blood monocytes. (B) The effect of nicotine to stimulate CD11b expression was dose-dependent and was abrogated by mecamylamine. Similar effects of nicotine on CD11a expression were observed by flow cytometry.
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