Annals of Oncology Advance Access originally published online on December 4, 2007
Annals of Oncology 2008 19(5):927-934; doi:10.1093/annonc/mdm550
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
gastrointestinal tumors |
Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation
1 Avicenne Hospital Assistance Publique-Hôpitaux de Paris and Paris XIII University (EA3412), Bobigny
2 Lariboisière Hospital AP-HP and Institut National de la Santé et de la Recherche Médicale U689, Cardiovascular Research Center, Paris, France
* Correspondence to: Prof. B. I. Levy, Cardiovascular Research Center, Institut National de la Santé et de la Recherche Médicale U689, 41 Boulevard de la Chapelle, 75010 Paris, France. Tel: +33-1-42958087; Fax: +33-1-42813128; E-mail: levy{at}larib.inserm.fr
Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP).
We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 ± 0.90 g).
Mean BP was increased after 6 months of therapy compared with baseline, from 129 ± 13/75 ± 7 mmHg to 145 ± 17/82 ± 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 ± 12 versus 83 ± 13/mm2; P < 0.0001), as well as pilocarpine-induced vasodilation (P < 0.05).
Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.
Key words: angiogenesis, capillary rarefaction, endothelial function, hypertension, microcirculation
Received for publication June 30, 2007. Revision received October 13, 2007. Revision received November 2, 2007. Accepted for publication November 5, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Bhargava VEGF kinase inhibitors: how do they cause hypertension? Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2009; 297(1): R1 - R5. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Shord, L. R. Bressler, L. A. Tierney, S. Cuellar, and A. George Understanding and managing the possible adverse effects associated with bevacizumab Am. J. Health Syst. Pharm., June 1, 2009; 66(11): 999 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Izzedine, S. Ederhy, F. Goldwasser, J. C. Soria, G. Milano, A. Cohen, D. Khayat, and J. P. Spano Management of hypertension in angiogenesis inhibitor-treated patients Ann. Onc., May 1, 2009; 20(5): 807 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A.M. van der Veldt, E. Boven, L. Vroling, H. J. Broxterman, A. J.M. van den Eertwegh, and J. G. Haanen Sunitinib-Induced Hemoglobin Changes Are Related to the Dosing Schedule J. Clin. Oncol., March 10, 2009; 27(8): 1339 - 1340. [Full Text] [PDF]
|
|
|
|
|
|
M. Scartozzi, E. Galizia, S. Chiorrini, R. Giampieri, R. Berardi, C. Pierantoni, and S. Cascinu Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab Ann. Onc., February 1, 2009; 20(2): 227 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Levy Blood pressure as a potential biomarker of the efficacy angiogenesis inhibitor Ann. Onc., February 1, 2009; 20(2): 200 - 203. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vilar, L. Waeckel, P. Bonnin, C. Cochain, C. Loinard, M. Duriez, J.-S. Silvestre, and B. I. Levy Chronic Hypoxia-Induced Angiogenesis Normalizes Blood Pressure in Spontaneously Hypertensive Rats Circ. Res., September 26, 2008; 103(7): 761 - 769. [Abstract] [Full Text] [PDF]
|
|