Vascular Injury Biomarkers

1 HISTORICAL CONTEXT OF DRUG-INDUCED VASCULAR INJURY AND DRUG DEVELOPMENT 

In humans, DIVI has been associated with most pharmaceutical classes of drug and often is not predicted from 

The mechanisms of preclinical DIVI can be grouped broadly into hemodynamic alterations through vasodilation or vasoconstriction, direct endothelial cell stimulation through on-target and off-target interactions and associated secondary lesions due to modulation of inflammatory mechanisms, and immune complex formation and complement activation, such 

Drug Discovery Toxicology From Target Assessment to Translational Biomarkers, First Edition. Edited by Yvonne Will, J. Eric McDuffie, Andrew J. Olaharski, and Brandon D. Jeffy. 

The categories for outcomes of DIVI are used to group phenotypic vascular findings according to histomorphologic similarities and candidate sensitive and specific biomarker response independent of etiology, mechanisms, and sites of injury (Zhang et al., 2012 Bendjama et al., 2014). 

---

Kerns W, et al. Drug-induced vascular injury - a quest for biomarkers. Toxicol Appl Pharmacol. 2005 203 62-87. 

A Note on Biomarkers of Vascular Injury Relevant to the Pancreas... 

Case Study 2 Drug Candidate-Induced Micro vascular Injury at the Exocrine-Endocrine Interface in the Rat with Unsuccessful Confirmation of Toxicity In Vitro and No Pancreas-Specific Monitorable Biomarkers Identified... 

Dahnas, D. A., Scicchitano, M. S., Mullins, D., Hughes-Earle, A., Tatsuoka, K., Magid-Slav, M., Frazier, K. S., and Thomas, H. C. (2011). Potential candidate genomic biomarkers of drug induced vascular injury in the rat. Toxicol Appl Pharmacol 257, 284-300. 

Keirstead, N., Bertinetti-Lapatki, C., Knapp, D., Albassam, M., Hughes, V., Hong, R, Roth, A., and Mikaelian, I. (2015). Temporal patterns of novel circulating biomarkers in IL-2-mediated vascular injury in the rat. Toxicol Pathol, 43, 984-94. 

Louden, C., Brott, D., Katein A, Kelly T., Gould, S., Jones, H., Betton, G., Valetin, J. R, and Richardson, R. J. (2006). Biomarkers and mechanisms of drug-induced vascular injury in non-rodents. Toxicol Pathol 34(1), 19-26. 

Zhang, J., Hanig, J. R, and De Felice, A. F. (2012). Biomarkers of endothelial cell activation Candidate markers for drug-induced vasculitis in patients or drug-induced vascular injury in animals. Vascul Pharmacol 56, 14-25. 

---