Neopterin: From Forgotten Biomarker to Leading Actor in Cardiovascular Pathophysiology

Abstract

Inflammation plays a role at all stages of atherosclerosis. Neopterin, a pteridine mainly synthesized by activated macrophages, is a marker of inflammation, immune system activation and an active participant in cardiovascular disease. Measurement of neopterin levels may help follow the evolution of specific inflammatory conditions (e.g. viral infection, renal transplant rejection, systemic inflammatory diseases, nephritic syndrome and autoimmune diseases). Serum levels of neopterin are elevated also in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Moreover, plasma levels of this molecule might predict adverse cardiovascular events in patients with CAD, acute coronary syndromes or severe PAD. In addition, neopterin levels are related to the development of heart failure. We provide an updated overview on neopterin and, its links with CAD, left ventricular dysfunction, and PAD. We also describe its potential role in cardiac regenerative strategies with using bone marrow cells.

Neopterin: A potential marker in chronic peripheral arterial disease

“…Thus, we hypothesize that N is useful in identifying the activated process of macrophage cells in patients with chronic PAD. It is known that different biomarkers of inflammation, such as interleukins or metalloproteinases are elevated both in chronic and more severe PAD patients (32)(33)(34)(35)(36)(37)(38). Results of this study have shown the involvement of activated macrophages in chronic arterial disease of the lower limbs, albeit not symptomatic.…”

Medical significance of simultaneous application of red blood cell distribution width (RDW) and neopterin as diagnostic/prognostic biomarkers in clinical practice

“…provides information about the cellular immune system activation [53][54][55][56]58] for the purpose of diagnosis, successful treatment and prognosis of inflammatory states, including atherosclerosis [56,59,60], malignancies (cancer and leukemia) [61], vascular (cardiovascular-, brain vascular, peripheral artery vascular) [59,62,63], neurological, autoimmune, and many other socially important diseases [e.g. acquired immune deficiency syndrome (AIDS); other viral and bacterial infections], aging-related disorders, including MS [56,57,60,[64][65][66][67][68][69][70].…”

“…In this respect, elevated neopterin concentrations correlated positively with increased plasma levels of hsCRP [69]. However, the direct contribution of CRP to atherogenesis is still unclear and debated [59]. The cellular and molecular mechanisms of a direct involvement of neopterin in atherogenesis through nuclear factor κB (NF-κB) could be better understood and clarified in the future, in view of its great potential as a bone marrow hematopoietic (granulocyte-macrophageal) growth factor, GM-CGF, as well as a bone marrow stromal cell growth factor [33,81,82].…”

Atherosclerosis in Primary Antiphospholipid Syndrome: Summary of Clinical and Pathogenic Evidence

“…Shedding of CD14 induced by serine proteases leads to a soluble CD14 (sCD14) present in plasma [48]. Neopterin (NPT) is produced in large amounts by human monocytes/macrophages upon stimulation with the cytokine interferon-γ released by activated T-lymphocytes [49]. Whereas mCD14 complex is expressed on macrophages and endothelial cells within the atherosclerotic plaque, plasma sCD14 shows no relation with stable coronary artery disease or carotid IMT [50][51][52][53][54].…”