title: Biomarkers for ischemic preconditioning: finding the responders.
abstract: Ischemic preconditioning is emerging as an innovative and novel cytoprotective strategy to counter ischemic vascular disease. At the root of the preconditioning response is the upregulation of endogenous defense systems to achieve ischemic tolerance. Identifying suitable biomarkers to show that a preconditioning response has been induced remains a translational research priority. Preconditioning leads to a widespread genomic and proteonomic response with important effects on hemostatic, endothelial, and inflammatory systems. The present article summarizes the relevant preclinical studies defining the mechanisms of preconditioning, reviews how the human preconditioning response has been investigated, and which of these bioresponses could serve as a suitable biomarker. Human preconditioning studies have investigated the effects of preconditioning on coagulation, endothelial factors, and inflammatory mediators as well as on genetic expression and tissue blood flow imaging. A biomarker for preconditioning would significantly contribute to define the optimal preconditioning stimulus and the extent to which such a response can be elicited in humans and greatly aid in dose selection in the design of phase II trials. Given the manifold biologic effects of preconditioning a panel of multiple serum biomarkers or genomic assessments of upstream regulators may most accurately reflect the full spectrum of a preconditioning response.
authors.affiliation: Miller School of Medicine, Department of Neurology, University of Miami, Miami, Florida, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Koch
authors.affiliation: 1] Miller School of Medicine, Department of Neurology, University of Miami, Miami, Florida, USA [2] Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy [3] IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Della-Morte
authors.affiliation: Miller School of Medicine, Department of Neurology, University of Miami, Miami, Florida, USA.
authors.forename: Kunjan R
authors.initials: KR
authors.lastname: Dave
authors.affiliation: Miller School of Medicine, Department of Neurology, University of Miami, Miami, Florida, USA.
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.affiliation: Miller School of Medicine, Department of Neurology, University of Miami, Miami, Florida, USA.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Perez-Pinzon
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D002545:Brain Ischemia / Q000097:blood* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002560:Cerebrovascular Circulation; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D019194:Ischemic Preconditioning; D040901:Proteomics; D057170:Translational Research, Biomedical
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators