New prognostic biomarkers in patients with ischemic stroke

Abstract

Ischemic stroke leads to disability and mortality and involved great consumption of resources. This review focuses on new prognostic biomarkers of mortality in patients with ischemic stroke in relation to the inflammation, coagulation, and oxidation. Blood concentration of tissue inhibitor of matrix metalloproteinases (TIMP)-1, soluble CD154 (sCD154), and malondialdehyde (MDA) in ischemic stroke patients have been recently found to be associated with mortality. Matrix metalloproteinases (MMPs) are zinc-containing endoproteinases involved in neuroinflammation during cerebral ischemia and TIMP-1 is the inhibitor of some of them. sCD154 is a member of the tumor necrosis factor (TNF) family that is released into circulation from different cells and when binding to their cell surface receptor showed proinflamatory and procoagulant properties. MDA is a low molecular weight aldehyde and appears due to the attacks from free radical to phospholipids of cellular membrane. The determination of circulating levels of those biomarkers could help in the prognostic classification of the patients. In addition, the modulation of those pathways could open new research lines for the treatment of ischemic stroke patients.Keywords: Ischemic stroke; biomarkers; TIMP-1; sCD154; malondialdehyde To cite this article: Leonardo Lorente. New prognostic biomarkers in patients with ischemic stroke. Mol Med Chem 2015; 1: e972. doi: 10.14800/mmc.972. IntroductionIschemic stroke leads to disability and mortality and involved great consumption of resources [1] . This review focuses on new prognostic biomarkers of mortality in patients with ischemic stroke in relation to the inflammation, coagulation, and oxidation. Tissue inhibitor of matrix metalloproteinases-1Matrix metalloproteinases (MMPs) are zinc-containing endoproteinases, which could be classified according to the substrate specificity in gelatinases (MMP-2 and MMP-9), collagenases (MMP-1, MMP-8 and MMP-13), stromelysins (MMP-3, MMP-10, MMP-11), matrilysins (MMP-7), elastases (MMP-12) and membrane-type (MMP-14, MMP-15, MMP-16 and MMP-17). MMPs are involved in the processes of degradation and remodelling of the extracellular matrix (ECM). MMP activity is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs are involved in physiological functions such as morphogenesis, tissue remodelling, menstrual cycle, and angiogenesis; and also in different diseases as tumour, arthritis, sepsis, and atherosclerosis [2] .Cerebral ischemia activate an inflammatory response and are released different cytotoxic agents, such as MMPs, which could favorate disruption of the blood-brain barrier (BBB) and cell damage [3] .There have been found higher circulating MMP-9 levels in ischemic stroke patients than in controls [4][5][6][7][8] , and also in patients with ischemic stroke and worse functional outcome compared with patients with better outcome [4][5][6][7][8][9][10][11][12] . Also, higher circulating levels of MMP-10 in ischemic stroke patients than in controls there have been f...