Introduction

To be considered a marker of hemodynamic stress, a molecule either must be induced by hemodynamic stress in vitro or in vivo or correlate with hemodynamic parameters in vivo and be detected in readily accessible body fluids such as plasma/serum or urine

From: Contemporary Cardiology: Cardiovascular Biomarkers: Pathophysiology and Disease Management Edited by: David A. Morrow © Humana Press Inc., Totowa, NJ

Potential Biomarkers

Fig. 1. Hemodynamic stress is a stimulus for the production of secreted proteins from several functional classes; when detected in plasma/serum, they are potential biomarkers of hemodynamic stress.

Potential Biomarkers

Fig. 1. Hemodynamic stress is a stimulus for the production of secreted proteins from several functional classes; when detected in plasma/serum, they are potential biomarkers of hemodynamic stress.

(Fig. 1). Many biomarkers of hemodynamic stress are secreted molecules that not only are induced by hemodynamic stress, but also have hemodynamic effects themselves. Thus, the biomarker represents hemodynamic state because it is induced for a compensatory function (often reduction in blood pressure [BP]). Regardless of its function or mechanism of action, a hemodynamic biomarker must be sufficiently stable that it can be detected during or shortly after the change in hemodynamic state.

Specificity is a critical issue with any biomarker, because predictive value will depend on specificity. Thus, we do not discuss herein molecules that are released from injured cells owing to loss of cell membrane integrity (e.g., fatty acid-binding proteins, heat-shock proteins, biopyrrin) or that might be induced by hemodynamic stress in vitro but are already well-established immune/inflammatory mediators of the cardiovascular system (e.g., CD40/CD40 ligand, interleukin [IL]-6, leukemia inhibitory factor, gp130, FAS/ FAS ligand) and thus are unlikely to reflect hemodynamic state specifically.

It is logical that some biomarkers of hemodynamic overload are themselves vasodilators or diuretics. To achieve BP hemostasis, an increase in arterial or venous pressures may be relieved by vasodilation or loss of intravascular volume. B-type natriuretic peptide (BNP) is the prototypical example of this group of biomarkers and has established the clinical relevance of hemodynamic biomarkers as a class. However, it is important to recognize that when hemodynamic state changes, multiple cardiac intracellular pathways are activated. Thus, the "hemodynamic defense reaction" (1), i.e., the response of the heart to hemodynamic overload, is not restricted to pathways that restore hemody-namic homeostasis. Neurohormonal-, inflammatory/immune-, growth-associated-, and cell-death-regulating mediators contribute to the short- and long-term responses to hemodynamic overload. Therefore, potential biomarkers of hemodynamic state and disease progression include many proteins outside the realm of vasomotion and diuresis, and new markers are likely to emerge from the laboratory as researchers further their understanding of how the heart responds to a change in mechanical stress.

This chapter begins with a description of ST2, a gene responsive to mechanical load in cardiac myocytes in vitro and a promising biomarker in acute myocardial infarction (AMI) and heart failure. Other novel hemodynamic markers discussed here are adrenomedullin, urocortin, urotensin, and myotrophin, which are currently being evaluated in the clinical setting. Finally, we describe why it is useful to apply the genomics approach to a well-characterized in vivo animal model of hemodynamic stress, a discovery strategy for identifying novel biomarkers.

Was this article helpful?

0 0

Post a comment