Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages

Abstract

High circulating levels of legumain in patients with stable or acute cardiovascular disease. • High circulating legumain in the acute phase is correlated with improved outcome. • Platelets contain, release and could be sources of circulating legumain. • Extracellular legumain mediates anti-inflammatory responses in primary monocytes.

Legumain in cardiovascular disease: Culprit or ally?

“…Consequently, legumain concentrations have been shown to be high in atherosclerotic plaques [8,9]. The current study by Lunde and colleagues [10] confirms these earlier findings, additionally showing for the first time a moderate association between circulating legumain concentrations and outcome in patients with ST elevation myocardial infarction (STEMI). Surprisingly, elevated legumain levels correlated with improved outcome upon STEMI.…”

“…In the current study, Lunde and colleagues point to a different position of legumain in the biological pathways involved in atherosclerosis and the presumed origin of its increased levels in the circulation [10]. First, legumain expression was not only confined to plaque macrophages but also colocalized with platelets in plaques as well as intraluminal thrombi from patients presenting with acute coronary or intracerebral events.…”

Mammalian legumain – A lysosomal cysteine protease with extracellular functions?

“…In this thesis both non-specific and specific methods have been used to detect proteins. thoroughly assessed and validated to be specific and sensitive towards legumain [33,43,237].…”

“…pro-and mature forms) concentrations in serum obtained from patients (paper III) and in conditioned media from in vitro cell cultures (paper II-IV). This ELISA kit is previously characterized for both inter-and intra-variable legumain detection [33,237].…”

“…On the other hand, by studying circulating levels of legumain from patients and legumain released from platelets, legumain was found in thrombus material retrieved from ruptured plaques and shown to be upregulated during acute cardiovascular events and associated with improved outcome [237]. Furthermore, stimulation of primary monocytes from healthy individuals with macrophage colony stimulating factor (M-CSF) and prolegumain lead to M2 polarization, increased secretion of the anti-inflammatory mediators CD163 and IL-10, and downregulation of the pro-inflammatory MCP-1 [237]. Also, FN is one of the first ECM proteins deposited at atherosclerosis sites and was proposed as a promoter of atherosclerotic lesion development [282].…”