Genes Involved in Hemorrhagic Transformations that Follow Recombinant T-Pa Treatment in Stroke Patients

Abstract

Aim: Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment. Our objective is to study the transcriptomics of HTs patients. Methods: We studied by microarrays 11 blood samples from patients with stroke that had received rt-PA of whom six of them had suffered a HT. For replication step RNA was collected from 14 new subjects (seven with HT, seven without) and then analyzed by real-time PCR. Four proteins were measured by ELISA in 72 new subjects to analyze their role as potential protein biomarkers. Results: The microarray analysis revealed that 14 genes were altered among the HT patients. The replication study confirmed these results for six genes. Two of them (BCL2 and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil processes. Conclusion: Our data revealed that genes related to apoptosis and neutrophil regulation pathways could be associated with HTs after rt-PA.

Original submitted 7 September 2012; Revision submitted 23 January 2013

KEYWORDS::

• hemorrhagic transformation
• microarrays
• rt-PA
• stroke
• transcription

Disclaimer

The Neurovascular Research Laboratory takes part in the International Stroke Genetics Consortium ISGC, the Spanish Stroke Genetics Consortium (www.genestroke.com) and in the Cooperative Neurovascular Research RENEVAS (RD06/0026/0010).

Financial & competing interests disclosure

This study was funded by a grant of the Spanish government (PI10/01212). A Rosell and P Delgado are supported by the Miguel Servet programme (CP09/00265 and CP09/136) from the Spanish Ministry of Health (Instituto de Salud Carlos III). The research leading to these results has received funding from the European Union‘s Seventh Framework Programme (FP7/2007-2013) under grant agreements #201024 and #202213 (European Stroke Network). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was funded by a grant of the Spanish government (PI10/01212). A Rosell and P Delgado are supported by the Miguel Servet programme (CP09/00265 and CP09/136) from the Spanish Ministry of Health (Instituto de Salud Carlos III). The research leading to these results has received funding from the European Union‘s SeventhFramework Programme (FP7/2007-2013) under grant agreements #201024 and #202213 (European Stroke Network). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interestin or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.