VAP-1/SSAO Plasma Activity and Brain Expression in Human Hemorrhagic Stroke

Hernández-Guillamón, Mar; Solé, Montse; Delgado, Pilar; García-Bonilla, Lidia; Giralt, Dolors; Boada, Cristina; Peñalba, Anna; García, Sandra; Flores, Alan; Ribó, Marc; Alvarez-Sabin, José; Ortega‐Aznar, Arantxa; Unzeta, Mercedes; Montaner, Joan

doi:10.1159/000333370

Cited by 41 publications

(26 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ICH patients, low VAP-1 independently predicted neurological improvement after 48 h (OR = 6.8) after accounting for baseline stroke characteristics [50]. This supports the finding that inhibition of VAP-1 activity in mice reduced brain cell destruction [51].…”

Section: Selection Of Blood Biomarkers In Ichsupporting

confidence: 68%

Potential Role of Blood Biomarkers in the Management of Nontraumatic Intracerebral Hemorrhage

Senn

Elkind

Montaner³

et al. 2014

Cerebrovasc Dis

Self Cite

View full text Add to dashboard Cite

Background: Intracerebral hemorrhage (ICH), a subtype of stroke associated with high mortality and disability, accounts for 13% of all strokes. Basic and clinical research has contributed to our understanding of the complex pathophysiology of neuronal injury in ICH. Outcome rates, however, remain stable, and questions regarding acute management of ICH remain unanswered. Newer research is aiming at matching measured levels of serum proteins, enzymes, or cells to different stages of brain damage, suggesting that blood biomarkers may assist in acute diagnosis, therapeutic decisions, and prognostication. This paper provides an overview on the most promising blood biomarkers and their potential role in the diagnosis and management of spontaneous ICH. Summary: Information was collected from studies, reviews, and guidelines listed in PubMed up to November 2013 on blood biomarkers of nontraumatic ICH in humans.We describe the potential role and limitations of GFAP, S100B/RAGE, and ApoC-III as diagnostic biomarkers, F-Amyloid as a biomarker for etiological classification, and 27 biomarkers for prognosis of mortality and functional outcome. Within the group of prognostic markers we discuss markers involved in coagulation processes (e.g., D-Dimers), neuroendocrine markers (e.g., copeptin), systemic metabolic markers (e.g., blood glucose levels), markers of inflammation (e.g., IL-6), as well as growth factors (e.g., VEGF), and others (e.g., glutamate). Some of those blood biomarkers are agents of pathologic processes associated with hemorrhagic stroke but also other diseases, whereas others play more distinct pathophysiological roles and help in understanding the basic mechanisms of brain damage and/or recovery in ICH. Key Messages: Numerous blood biomarkers are associated with different pathophysiological pathways in ICH, and some of them promise to be useful in the management of ICH, eventually contributing additional information to current tools for diagnosis, therapy monitoring, risk stratification, or intervention. Up to date, however, no blood biomarker of ICH has been studied sufficiently to find its way into clinical routine yet; well-designed, large-scale, clinical studies addressing relevant clinical questions are needed. We suggest that the effectiveness of biomarker research in ICH might be improved by international cooperation and shared resources for large validation studies, such as provided by the consortium on stroke biomarker research (http://stroke-biomarkers.com/page.php?title=Resources). i 2014 S. Karger AG, Basel

show abstract

Section: Selection Of Blood Biomarkers In Ichsupporting

confidence: 68%

Potential Role of Blood Biomarkers in the Management of Nontraumatic Intracerebral Hemorrhage

Senn

Elkind

Montaner³

et al. 2014

Cerebrovasc Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Consistent with this hypothesis, soluble SSAO/VAP-1 release was observed in our stroke experimental model after OGD with reoxygenation. Interestingly, the maximal increase in plasma SSAO activity in hemorrhagic stroke patients is observed 4-6 h after symptom onset [20]. In our experimental model, soluble SSAO/VAP-1 release was mainly observed after reoxygenation, at similar time points than in humans, and matching the strongest occurrence of endothelial cell death.…”

Section: Discussionmentioning

confidence: 67%

“…Some authors have reported that 3T3-L1 adipocytes are able to release soluble SSAO by an MMP-dependent shedding mechanism [28], whereas batimastat, a broad-spectrum MMP inhibitor, avoided any SSAO release. In the periinfarcted region of stroke patients' brains, a decrease in the frequency of SSAO/VAP-1-containing vessels has been found [19,20]. In this regard, it has been suggested that mediators present in cerebrovascular pathologies such as stroke could become a stimulus to activate SSAO/VAP-1 shedding.…”

Section: Discussionmentioning

confidence: 99%

“…The mediators that induce these alterations in SSAO/VAP-1 levels are still unknown, but it is believed that increased SSAO/VAP-1 levels contribute to the physiopathology of these diseases by overproducing harmful agents [16,17,18]. In addition, human plasma SSAO activity is a strong predictor of parenchymal hemorrhages after tissue plasminogen activator treatment in ischemic stroke patients [19], and plasma SSAO activity, also elevated in hemorrhagic stroke patients, predicts their neurological outcome [20]. Despite this evidence, the role of SSAO/VAP-1 in stroke is still far from clear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of SSAO/VAP-1 in Oxygen-Glucose Deprivation-Mediated Damage Using the Endothelial hSSAO/VAP-1-Expressing Cells as an Experimental Model of Cerebral Ischemia

Sun

Solé²,

Unzeta³

2014

Cerebrovasc Dis

Self Cite

View full text Add to dashboard Cite

Background: In the acute phase of ischemic stroke, endothelial cells are activated and induce the expression of adhesion molecules. Vascular adhesion protein 1 (VAP-1) is a proinflammatory protein that mediates leukocyte recruitment through its semicarbazide-sensitive amine oxidase (SSAO) activity (EC 1.4.3.21). Plasmatic SSAO activity predicts the appearance of parenchymal hemorrhages after tissue plasminogen activator treatment in ischemic stroke patients, and it is increased as well in hemorrhagic stroke patients. The aim of this study has been to elucidate the role of SSAO/VAP-1 present in endothelial cells during ischemic stroke conditions. Methods: Based on the use of endothelial cells expressing, or not expressing, the human SSAO/VAP-1 protein, we have set up an easy ischemic model using oxygen-glucose deprivation (OGD) as an experimental approach to the stroke process. Different OGD and reoxygenation conditions have been analyzed. Western blotting has been used to analyze the activated apoptotic pathways. Several metalloproteinase inhibitors were also used to determine their role in the SSAO/VAP-1 release from the membrane of endothelial cells to the culture media, as a soluble form. Adhesion assays were also performed in order to assess the SSAO/VAP-1-dependent leukocyte adhesion to the endothelia under different OGD and reoxygenation conditions. Results: Our results show that SSAO/VAP-1 expression increases the susceptibility of endothelial cells to OGD, and that its enzymatic activity, through specific substrate oxidation, increases vascular cell damage under these experimental conditions. Caspase-3 and caspase-8 are activated during the death process. In addition, OGD constitutes a stimulus for soluble SSAO/VAP-1 release, partly mediated by metalloproteinase-2-dependent shedding. Short-time OGD induces SSAO/VAP-1-dependent leukocyte binding on endothelial cells, which is partly dependent on its enzymatic activity. Conclusions: Our results show that SSAO/VAP-1 could participate in some of the processes occurring during stroke. Its expression in endothelial cells increases the OGD-associated cell damage. SSAO/VAP-1 mediates also part of the tissue damage during the reoxygenation process by oxidizing its known enzymatic substrate, methylamine. Also, OGD constitutes a stimulus for its soluble-form release, found elevated in many pathological conditions including stroke. OGD induces SSAO-dependent leukocyte-binding activity, which may have consequences in disease progression, since leukocyte infiltration has shown a determinant role in cerebral ischemia. For all the stroke-related processes in which SSAO/VAP-1 participates, it would be an interesting therapeutic target. Therefore, this model will be a very useful tool for the screening of new molecules as therapeutic agents for cerebral ischemia.

show abstract

“…Therefore, VAP-1 inhibition may protect against tPA-induced vascular damage by inhibiting leukocyte infiltration. Recently, the same group found plasma VAP-1/SSAO activity is increased in hemorrhagic stroke patients and may be a predictor for neurological outcome after ICH [104]. All of these clinical reports suggest VAP-1 is a potential therapeutic target for ICH-induced brain injury.…”

Section: Adhesion Cascade In Cns Disordersmentioning

confidence: 99%

Adhesion Molecules in CNS Disorders: Biomarker and Therapeutic Targets

Ma¹,

Chen²,

Klebe³

et al. 2013

CNSNDDT

View full text Add to dashboard Cite

Mounting evidence has been provided regarding the crucial role of leukocyte extravasation and subsequent inflammatory response in several central nervous system (CNS) disorders. The infiltrated leukocytes release pro-inflammatory mediators and activate resident cells, leading to tissue injury. Leukocyte-endothelia interaction is critical for leukocyte extravasation and migration from the intravascular space into the tissue during inflammation. The basic physiology of leukocyte-endothelia interaction has been investigated extensively. Traditionally, three kinds of adhesion molecules, selectin, integrin, and immunoglobulin families, are responsible for this multiple-step interaction. Furthermore, blocking adhesion molecule function by genetic knockout, antagonizing antibodies, or inhibitory pharmacological drugs provides neuroprotection, which is associated with a reduction in leukocyte accumulation with in the tissue. Detection of the soluble form of adhesion molecules has also been proven to predict outcomes in CNS disorders. Lately, vascular adhesion protein-1 (VAP-1), a novel adhesion molecule and endothelial cell surface enzyme, has been implicated as a brake during leukocyte extravasation. In this review, we summarize the functions of traditional adhesion molecules as well as VAP-1 in the leukocyte adhesion cascade. We also discuss the diagnostic and therapeutic potential of adhesion molecules in CNS disorders.

show abstract

VAP-1/SSAO Plasma Activity and Brain Expression in Human Hemorrhagic Stroke

Cited by 41 publications

References 63 publications

Potential Role of Blood Biomarkers in the Management of Nontraumatic Intracerebral Hemorrhage

Potential Role of Blood Biomarkers in the Management of Nontraumatic Intracerebral Hemorrhage

Involvement of SSAO/VAP-1 in Oxygen-Glucose Deprivation-Mediated Damage Using the Endothelial hSSAO/VAP-1-Expressing Cells as an Experimental Model of Cerebral Ischemia

Adhesion Molecules in CNS Disorders: Biomarker and Therapeutic Targets

Contact Info

Product

Resources

About