Faculty Collaboration Database

Evaluation of von Willebrand factor and von Willebrand factor propeptide in models of vascular endothelial cell activation, perturbation, and/or injury. Toxicol Pathol 2014 Jun;42(4):672-83

Date

02/07/2014

Pubmed ID

24499802

Pubmed Central ID

PMC4222990

DOI

10.1177/0192623313518664

Scopus ID

2-s2.0-84902078130 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Pharmacologically, vasoactive agents targeting endothelial and/or smooth muscle cells (SMC) are known to cause acute drug-induced vascular injury (DIVI) and the resulting pathology is due to endothelial cell (EC) perturbation, activation, and/or injury. Alteration in EC structure and/or function may be a critical event in vascular injury and, therefore, evaluation of the circulatory kinetic profile and secretory pattern of EC-specific proteins such as VWF and VWFpp could serve as acute vascular injury biomarkers. In rat and dog models of DIVI, this profile was determined using pharmacologically diverse agents associated with functional stimulation/perturbation (DDAVP), pathological activation (lipopolysaccharide [LPS]/endotoxin), and structural damage (fenoldopam [FD], dopamine [DA], and potassium channel opener (PCO) ZD6169). In rats, FD caused moderate DIVI and time-related increase in plasma VWF levels ∼33% while in control rats VWF increased ∼5%. In dogs, VWF levels transiently increased ∼30% when there was morphologic evidence of DIVI by DA or ZD6169. However, in dogs, VWFpp increased >60-fold (LPS) and >6-fold (DDAVP), respectively. This was in comparison to smaller dynamic 1.38-fold (LPS) and 0.54-fold (DDAVP) increases seen in plasma VWF. Furthermore, DA was associated with a dose-dependent increase in plasma VWFpp. In summary, VWF and VWFpp can discriminate between physiological and pathological perturbation, activation, and injury to ECs.

Author List

Brott DA, Katein A, Thomas H, Lawton M, Montgomery RR, Richardson RJ, Louden CS

Author

Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Amides
Animals
Benzophenones
Biomarkers
Blood Platelets
Dogs
Dopamine
Drug-Related Side Effects and Adverse Reactions
Endothelial Cells
Female
Fenoldopam
Male
Phlebotomy
Protein Precursors
Rats
Rats, Wistar
Vascular System Injuries
von Willebrand Factor