Evaluation of von Willebrand Factor and von Willebrand Factor Propeptide in Models of Vascular Endothelial Cell Activation, Perturbation, and/or Injury
| Autor: | Michael T. Lawton, Rudy J. Richardson, Calvert Louden, Robert R. Montgomery, Heath C. Thomas, Anne M. Katein, David Brott |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Blood Platelets
Male medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Fenoldopam Lipopolysaccharide Dopamine Administration Oral Stimulation Toxicology Article Pathology and Forensic Medicine Benzophenones chemistry.chemical_compound Dogs Phlebotomy Von Willebrand factor Internal medicine von Willebrand Factor medicine Animals Platelet Protein Precursors Rats Wistar Molecular Biology biology Endothelial Cells Cell Biology Vascular System Injuries Amides Rats Endothelial stem cell Endocrinology chemistry Circulatory system biology.protein Female Potassium channel opener Biomarkers medicine.drug |
| Zdroj: | Toxicologic Pathology. 42:672-683 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|