Heat shock proteins as biomarkers for the rapid detection of brain and spinal cord ischemia: a review and comparison to other methods of detection in thoracic aneurysm repair

Abstract

The heat shock proteins (HSPs) are members of highly conserved families of molecular chaperones that have multiple roles in vivo. We discuss the HSPs in general, and Hsp70 and Hsp27 in particular, and their rapid induction by severe stress in the context of tissue and organ expression in physiology and disease. We describe the current state of knowledge of the relationship and interactions between extra-and intracellular HSPs and describe mechanisms and significance of extracellular expression of HSPs. We focus on the role of the heat shock proteins as biomarkers of central nervous system (CNS) ischemia and other severe stressors and discuss recent and novel technologies for rapid measurement of proteins in vivo and ex vivo. The HSPs are compared to other proposed small molecule biomarkers for detection of CNS injury and to other methods of detecting brain and spinal cord ischemia in real time. While other biomarkers may be of use in prognosis and in design of appropriate therapies, none appears to be as rapid as the HSPs; therefore, no other measurement appears to be of use in the immediate detection of ongoing severe ischemia with the intention to immediately intervene to reduce the severity or risk of permanent damage.

Persistently elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker in post-cardiac-arrest patients

“…Elevated HSP70 in the serum or tissues appears to be a nonspecific indicator of organ ischemia or dysfunction. HSP70 is valuable as an immediate, secreted biomarker of critical, ongoing cellular ischemia in brain and spinal cord ischemia models (Hecker and McGarvey 2011). Our work group demonstrated previously that serum HSP70 levels are associated with disease severity in chronic heart failure patients, but did not find correlation between HSP70 and CRP, TNF-alpha or IL-6 (Gombos et al 2008).…”

“…The possible role of HSP70 as a biomarker of cellular damage in ischemia of the brain and spinal cord has been reviewed recently (Hecker and McGarvey 2011). HSP70 is particularly valuable as an immediate, secreted biomarker in cellular ischemia.…”

“…HSP70 plays multiple roles in cellular homeostasis. Its level increases rapidly in response to various types of severe stress, as a protection against a subsequent, nearlethal, ischemic or hypoxic event (Hecker and McGarvey 2011). Besides, it is involved in the folding of proteins, their transport between cellular compartments, and in the breakdown of the irreversibly damaged ones.…”

“…Reliable biomarkers of brain ischemia and of reperfusion injury are the S100 protein B (S100B), and the neuronspecific enolase (NSE); a strong correlation exists between these markers and in the prognosis of post-cardiac-arrest patients (Shinozaki et al 2009). Recently, Hecker et al reviewed the potential of HSP70 as a biomarker for the rapid detection of brain and spinal cord ischemia (Hecker and McGarvey 2011). Elevated serum HSP70 levels of patients with severe traumatic brain injury predicted death within 20 h after injury (da Rocha et al 2005).…”

Quantitative Analyses of Postmortem Heat Shock Protein mRNA Profiles in the Occipital Lobes of Human Cerebral Cortices: Implications in Cause of Death

“…To test this idea, we primarily focus on brain tissues because neuronal cells abundantly express HSPs and are highly vulnerable to a variety of cellular stresses, such as hypoxia/anoxia as well as disturbances in energy homeostasis (Hecker and McGarvey, 2011;Stetler et al, 2010). Furthermore, brain tissues also have a practical advantage in postmortem RNA profiling; it has been demonstrated that postmortem gene transcripts in brain tissues are relatively stable and intact with longer PMI, and are thus suitable for extraction and quantitative analyses of RNA (Heinrich et al, 2007a;2007b;Leonard et al, 1993;Popova et al, 2008).…”