Neuraminidases—Key Players in the Inflammatory Response after Pathophysiological Cardiac Stress and Potential New Therapeutic Targets in Cardiac Disease

SIMPLE SUMMARY: In this manuscript, we review research performed on enzymes called neuraminidases (NEUs) and the consequences of their activity on the heart muscle and on a few of its pathophysiological diseases. NEUs are able to cleave off sugars termed sialic acids, which are terminally attached to glycolipids and -proteins. Due to their outermost location, the level of sialic acids affects communication between cells, which in turn affects inflammatory responses. Thus, NEUs hold regulatory features influencing multiple processes within the body. The involvement of NEUs in cardiovascular pathologies i.e., atherosclerosis, myocardial infarction (MI), cardiomyopathies (CMs) and coronary artery disease (CAD) has been investigated and the activity of NEUs or rather the resulting sialic acid level has been identified as a diagnostic biomarker for cardiovascular disease. The downregulation of NEU activity in different animal models diminished inflammation, ameliorated cardiac function and improved vascular health, altogether identifying targeting NEU as a new promising treatment option for cardiac diseases. Fortunately, antiviral drugs blocking the activity of NEUs are already an established therapeutic regime in the treatment of influenza. First clinical trials using NEU inhibitor oseltamivir in patients with chronic heart failure are already ongoing. ABSTRACT: Glycoproteins and glycolipids on the cell surfaces of vertebrates and higher invertebrates contain α-keto acid sugars called sialic acids, terminally attached to their glycan structures. The actual level of sialylation, regulated through enzymatic removal of the latter ones by NEU enzymes, highly affects protein-protein, cell-matrix and cell-cell interactions. Thus, their regulatory features affect a large number of different cell types, including those of the immune system. Research regarding NEUs within heart and vessels provides new insights of their involvement in the development of cardiovascular pathologies and identifies mechanisms on how inhibiting NEU enzymes can have a beneficial effect on cardiac remodelling and on a number of different cardiac diseases including CMs and atherosclerosis. In this regard, a multitude of clinical studies demonstrated the potential of N-acetylneuraminic acid (Neu5Ac) to serve as a biomarker following cardiac diseases. Anti-influenza drugs i.e., zanamivir and oseltamivir are viral NEU inhibitors, thus, they block the enzymatic activity of NEUs. When considering the improvement in cardiac function in several different cardiac disease animal models, which results from NEU reduction, the inhibition of NEU enzymes provides a new potential therapeutic treatment strategy to treat cardiac inflammatory pathologies, and thus, administrate cardioprotection.