Biomarkers of drug-induced vascular injury

Brott, David; Gould, Sarah; Jones, Huw B.; Schofield, Jason; Prior, Helen; Valentin, Jean Pierre; Bjurström, Sivert; Kenne, Kerstin; Schuppe‐Koistinen, Ina; Katein, Anne

doi:10.1016/j.taap.2005.04.028

Cited by 43 publications

(24 citation statements)

References 15 publications

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“…As was previously reported (Brott et al 2005), immunoreactivity to VWF was present in all vessels with microscopic evidence of vascular injury (Figure 6). In injured vessels, the signal strength of extravascular VWF immunoreactivity correlated with the histopathology grade of severity.…”

Section: Resultssupporting

confidence: 87%

Evaluation of von Willebrand Factor and von Willebrand Factor Propeptide in Models of Vascular Endothelial Cell Activation, Perturbation, and/or Injury

et al. 2014

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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.

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Section: Resultssupporting

confidence: 87%

Evaluation of von Willebrand Factor and von Willebrand Factor Propeptide in Models of Vascular Endothelial Cell Activation, Perturbation, and/or Injury

et al. 2014

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“…This observation in conjunction with other reports raise the possibility that the transient 2-6-hour increase in circulating plasma vWF could be a reporter of endothelial cell activation/perturbation prior to morphologic evidence of vascular damage (Newsholme et al, 2000). However, plasma vWF values returned to baseline or lower 24 hours postdosing when vascular damage was confirmed histologically (Brott et al, 2005b). These data clearly indicate that there is a temporal disconnect, between increases in plasma vWF, the time when morphologic evidence of vascular injury is present and progression of the lesion characterized by inflammation secondarily.…”

Section: Vwf and Vwfppsupporting

confidence: 75%

Biomarkers and Mechanisms of Drug-Induced Vascular Injury in Non-Rodents

et al. 2006

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In preclinical safety studies, drug-induced vascular injury can negatively impact candidate-drug selection because there are no obvious diagnostic markers for monitoring this pathology preclinically or clinically. Furthermore, our current understanding of the pathogenesis of this lesion is limited. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary target cells, smooth muscle (SMC) and endothelial cell (EC), are unknown. Evaluation of potential novel markers for clinical monitoring with a mechanistic underpinning would add value in risk assessment and risk management. This mini review focuses on the efforts and progress to identify diagnostic markers as well as understanding the mechanism of action in nonrodent drug-induced vascular injury.

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“…An inverse relationship between neointima formation and caveolin-1 has been also demonstrated in other animal models, as well as in humans. Decreased expression of caveolin-1 has been reported in the neointima induced in arteries of animal models [92,93,106] following balloon angioplasty and in the atheromas of human carotid arteries [91,94], as compared to SMCs in the medial layer.…”

Section: Caveolae/caveolin and Smc Proliferationmentioning

confidence: 96%

Caveolae and Caveolin-1: Novel Potential Targets for the Treatment of Cardiovascular Disease

Frank¹,

Hassan²,

Rodríguez-Feo³

et al. 2007

CPD

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Caveolae are 50-100 nm cell surface plasma membrane invaginations that are highly enriched in cholesterol and sphingolipids and are characterized by the protein marker caveolin-1. Caveolin-1 is highly expressed in terminally differentiated cells. Among these cells, endothelial cells, smooth muscle cells, and macrophages have all been shown to play key roles in the development of vascular disease. Atherosclerosis and neointimal formation are two major processes that have been associated with arterial occlusion. In both cases, caveolin-1 has been shown to play an important role. However, depending on the cell type and the metabolic pathways regulated by this protein, caveolin-1 may positively or negatively influence the development of vascular disease. Both of these aspects will be discussed in this review.

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Biomarkers of drug-induced vascular injury

Cited by 43 publications

References 15 publications

Evaluation of von Willebrand Factor and von Willebrand Factor Propeptide in Models of Vascular Endothelial Cell Activation, Perturbation, and/or Injury

Evaluation of von Willebrand Factor and von Willebrand Factor Propeptide in Models of Vascular Endothelial Cell Activation, Perturbation, and/or Injury

Biomarkers and Mechanisms of Drug-Induced Vascular Injury in Non-Rodents

Caveolae and Caveolin-1: Novel Potential Targets for the Treatment of Cardiovascular Disease

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