Busulphan-cyclophosphamide cause endothelial injury, remodeling of resistance arteries and enhanced expression of endothelial nitric oxide synthase

Sulaiman Al-Hashmi, Piet J M Boels, Fahad Zadjali, Behnam Sadeghi, Johan Sällström, Kjell Hultenby, Zuzana Hassan, Anders Arner, Moustapha Hassan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Stem cell transplantation (SCT) is a curative treatment for malignant and non malignant diseases. However, transplantation-related complications including cardiovascular disease deteriorate the clinical outcome and quality of life. We have investigated the acute effects of conditioning regimen on the pharmacology, physiology and structure of large elastic arteries and small resistance-sized arteries in a SCT mouse model. Mesenteric resistance arteries and aorta were dissected from Balb/c mice conditioned with busulphan (Bu) and cyclophosphamide (Cy). In vitro isometric force development and pharmacology, in combination with RT-PCR, Western blotting and electron microscopy were used to study vascular properties. Compared with controls, mesenteric resistance arteries from the Bu-Cy group had larger internal circumference, showed enhanced endothelium mediated relaxation and increased expression of endothelial nitric oxide synthase (eNOS). Bu-Cy treated animals had lower mean blood pressure and signs of endothelial injury. Aortas of treated animals had a higher reactivity to noradrenaline. We conclude that short-term consequences of Bu-Cy treatment divergently affect large and small arteries of the cardiovascular system. The increased noradrenaline reactivity of large elastic arteries was not associated with increased blood pressure at rest. Instead, Bu-Cy treatment lowered blood pressure via augmented microvascular endothelial dependent relaxation, increased expression of vascular eNOS and remodeling toward a larger lumen. The changes in the properties of resistance arteries can be associated with direct effects of the compounds on vascular wall or possibly indirectly induced via altered translational activity associated with the reduced hematocrit and shear stress. This study contributes to understanding the mechanisms that underlie the early effects of conditioning regimen on resistance arteries and may help in designing further investigations to understand the late effects on vascular system.

Original languageEnglish
Article numbere30897
JournalPLoS One
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 27 2012

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Busulfan
cyclophosphamide
Nitric Oxide Synthase Type III
Cyclophosphamide
arteries
Arteries
Blood pressure
Blood Vessels
Wounds and Injuries
Stem cells
Mesenteric Arteries
blood vessels
Stem Cell Transplantation
Blood Pressure
Norepinephrine
Animals
cell transplantation
Aorta
pharmacology
norepinephrine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Busulphan-cyclophosphamide cause endothelial injury, remodeling of resistance arteries and enhanced expression of endothelial nitric oxide synthase. / Al-Hashmi, Sulaiman; Boels, Piet J M; Zadjali, Fahad; Sadeghi, Behnam; Sällström, Johan; Hultenby, Kjell; Hassan, Zuzana; Arner, Anders; Hassan, Moustapha.

In: PLoS One, Vol. 7, No. 1, e30897, 27.01.2012.

Research output: Contribution to journalArticle

Al-Hashmi, Sulaiman ; Boels, Piet J M ; Zadjali, Fahad ; Sadeghi, Behnam ; Sällström, Johan ; Hultenby, Kjell ; Hassan, Zuzana ; Arner, Anders ; Hassan, Moustapha. / Busulphan-cyclophosphamide cause endothelial injury, remodeling of resistance arteries and enhanced expression of endothelial nitric oxide synthase. In: PLoS One. 2012 ; Vol. 7, No. 1.
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