Cytokines and matrix metalloproteinases as potential biomarkers in chronic heart failure

Heart failure (HF) is accompanied by the upregulation of bioactive signaling molecules, known as cytokines, and a family of downstream proteases, matrix metalloproteinases (MMPs). It is now apparent that these molecules contribute to adverse myocardial remodeling during HF. Elevated levels of cytokines and MMPs exist in the myocardium and can subsequently spill over into the systemic circulation. The purpose of this article is to examine clinical studies of HF that have quantified levels of different types of cytokines, MMPs and endogenous tissue inhibitors of MMPs in relation to this disease process. HF is a complex syndrome that can develop from various etiologies and can be characterized into two distinct phenotypes: systolic and diastolic. This article will present recent clinical studies that have identified significant differences between the cytokine and MMP circulating profile of systolic and diastolic HF patients. In general, elevated levels of cytokines and MMPs exist in systolic HF patients when compared with diastolic HF patients, whereas diastolic HF patients have elevated levels of cytokines and MMPs when compared with controls. Therefore, future studies distinguishing between HF phenotypes may provide more consistent results in determining possible analytes to be used as biomarkers. Furthermore, this article will emphasize why standardization of analytical techniques and establishment of referent cytokine and MMP levels are necessary if these analytes are to be used as biomarkers for the diagnosis, prognosis and evaluation of treatment in the context of HF.