Application of proteomics to cerebrovascular disease

Abstract

While neurovascular diseases such as ischemic and hemorrhagic stroke are the leading causes of disability in the world, the repertoire of therapeutic interventions has remained remarkably limited. There is a dire need to develop new diagnostic, prognostic, and therapeutic options. The study of proteomics is particularly enticing for cerebrovascular diseases such as stroke, which most likely involve multiple gene interactions resulting in a wide range of clinical phenotypes. Currently, rapidly progressing neuroproteomic techniques have been employed in clinical and translational research to help identify biologically relevant pathways, to understand cerebrovascular pathophysiology, and to develop novel therapeutics and diagnostics. Future integration of proteomic with genomic, transcriptomic, and metabolomic studies will add new perspectives to better understand the complexities of neurovascular injury. Here, we review cerebrovascular proteomics research in both preclinical (animal, cell culture) and clinical (blood, urine, cerebrospinal fluid, microdialyates, tissue) studies. We will also discuss the rewards, challenges, and future directions for the application of proteomics technology to the study of various disease phenotypes. To capture the dynamic range of cerebrovascular injury and repair with a translational targeted and discovery approach, we emphasize the importance of complementing innovative proteomic technology with existing molecular biology models in preclinical studies, and the need to advance pharmacoproteomics to directly probe clinical physiology and gauge therapeutic efficacy at the bedside.

Figure 1

Proteomic methodologies used to study cerebrovascular disease in publications reviewed. Methods were grouped into three categories: (i) Expression Profiling—discovery approach using shotgun MS analysis with in-gel or LC separation; (ii) Comparative/Quantitative Proteomics—semiquantitative isotope labeled and label-free technique for tissue and cell media; (iii) Validation—targeted quantitative approaches measuring specific protein level using antibody based and nonantibody-based methods. DIGE, 2D difference gel electrophoresis; SELDI-TOF, surface-enhanced laser desorption/ionization time-of-flight; SILAC, stable isotope labeling with amino acids in cell culture; C12/13 acrylamide; iTRAQ, isobaric tags for relative and absolute quantification; TMT, tandem mass tags; WB, Western blot; IHC, immunohistochemistry; SRM, selected reaction monitoring; MRM, multiple reaction monitoring.