Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community

Efforts at reducing cardiovascular events rely on the accurate identification of individuals at risk. Unfortunately, patients who experience cardiovascular events often have a paucity of traditional factors predictive of cardiovascular disease (CVD) to facilitate recognition of risk. In this regard, measurement of circulating biomarkers has been examined as an option for assessing risk for cardiovascular events beyond standard risk factors. Although potentially useful to predict and reclassify risk in some cohorts, studies of such testing for predicting cardiovascular events in low to intermediate risk populations have returned mixed results, suggesting further efforts are needed to better understand the role of testing of circulating substances for risk prediction in such patients. Beyond potential clinical application, biomarker measurement has also been leveraged as a tool to understand mechanism of CVD onset. More studies of novel and established circulating markers of disease are thus needed, both to advance understanding of optimal means for risk stratification and supplement knowledge about mechanism of disease. Neurotensin is a 13-amino acid peptide originally isolated from bovine hypothalamic and later from intestinal tissue. Neurotensin has a wide range of biological roles in the body, notably including a broad range of effects on the cardiovascular system; these include regulation of heart rate, myocardial contractility, and vascular tone. Effects of neurotensin are transduced primarily through 3 receptors: the G-protein– coupled NTS1 and NTS2 receptors and the non–G-protein–coupled NTS3, otherwise known as sortilin receptor 1 (SORT1), a member of the Vps10p-domain receptor family. SORT1 (also known as sortilin) is involved in the binding of several unrelated ligands, and it plays an important role in hepatic secretion of very low–density lipoprotein cholesterol