Cardiovascular Toxicology

, Volume 19, Issue 1, pp 36–47 | Cite as

Increased Plasma Nitrite and von Willebrand Factor Indicates Early Diagnosis of Vascular Diseases in Chemotherapy Treated Cancer Patients

  • Suvendu Giri
  • Jagadesh Chandra Bose
  • Ajay Chandrasekar
  • Basant K. Tiwary
  • Palanivel GajalakshmiEmail author
  • Suvro ChatterjeeEmail author


Chemotherapy induced cardiotoxicity leads to development of hypertension, conduction abnormalities, and congestive heart failure. However, there is no simple test to detect and assess cardiovascular risk in a chemotherapy treated cancer patient. The aim of the present study on cancer patients treated with (n = 66) and without (n = 66) chemotherapy is to identify indicators from plasma for vascular injury. The levels of plasma nitrite, asymmetric dimethyl arginine (ADMA), von Willebrand factor (vWF), cardiac troponins, lipid peroxidation (MDA), and lactate dehydrogenase (LDH) were estimated. An R package, namely, Optimal Cutpoints, and a machine learning method—support vector machine (SVM) were applied for identifying the indicators for cardiovascular damage. We observed a significant increase in nitrite (p < 0.001) and vWF (p < 0.001) level in chemotherapy treated patients compared to untreated cancer patients and healthy controls. An increased MDA and LDH activity from plasma in chemotherapy treated cancer patients was found. The R package analysis and SVM model developed using three indicators, namely, nitrite, vWF, and MDA, can distinguish cancer patients before and after chemotherapy with an accuracy of 87.8% and AUC value of 0.915. Serum collected from chemotherapy treated patients attenuates angiogenesis in chick embryo angiogenesis (CEA) assay and inhibits migration of human endothelial cells. Our work suggests that measurement of nitrite along with traditional endothelial marker vWF could be used as a diagnostic strategy for identifying susceptible patients to develop cardiovascular dysfunctions. The results of the present study offer clues for early diagnosis of subclinical vascular toxicity with minimally invasive procedure.

Graphical Abstract

Schematic representation of chemotherapy induced elevated plasma nitrite level in cancer patients.


Chemotherapy Nitrite von Willebrand factor Cardiotoxicity Vascular disease Support vector machine (SVM) 



This work is financially supported by DBT (File No. 6242-P100/RGCB/PMD/DBT/GJLM/2015) Government of India. S.G. acknowledges financial support from DST, Govt. of India for INSPIRE fellowship. P.G. thanks UGC for post-doctoral fellowship to women. S.C. acknowledges a Grant from University Grants Commission - Faculty Recharge Programme, (UGC-FRP), Government of India.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical Approval

All procedures carried out in the present study are in accordance with the 1964 Helsinki declaration. The study was also approved by the Institutional Ethics Committee, Rajiv Gandhi Government General Hospital (Ref no. 1482), and Institutional Biosafety & Ethical Committee of AU-KBC Research Centre, Chennai, India.

Informed Consent

Patients were recruited after obtaining individual written informed consent.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Suvendu Giri
    • 1
  • Jagadesh Chandra Bose
    • 2
  • Ajay Chandrasekar
    • 2
  • Basant K. Tiwary
    • 3
  • Palanivel Gajalakshmi
    • 4
    Email author
  • Suvro Chatterjee
    • 1
    • 4
    Email author
  1. 1.Department of BiotechnologyAnna UniversityChennaiIndia
  2. 2.Madras Medical CollegeRajiv Gandhi Government General HospitalChennaiIndia
  3. 3.Centre for BioinformaticsPondicherry UniversityPondicherryIndia
  4. 4.AU-KBC Research CentreAnna UniversityChennaiIndia

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