25.03.2022A novel biomarker that originates from an endothelial scavenger receptor was found to by highly predictive for fatal events and plaque progression in patients with ACS

In collaboration with the SPUM-ACS consortium members of the Center for Molecular Cardiology identified a novel biomarker of plaque vulnerability, progression and adverse outcomes in patients with acute coronary syndromes. Indeed, human atherosclerotic plaques express high levels of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), with plaque regions particularly prone for instability showing accentuated LOX-1 abundance. The pro-inflammatory milieu within atherosclerotic plaques enhances LOX-1 synthesis, promotes LOX-1 shedding and thus soluble LOX-1 (sLOX-1) release. The turnover of membrane-bound LOX-1 determines plaque composition and thus stability, with systemically circulating sLOX-1 emerging as a novel biomarker reflecting plaque burden and vulnerability. In this multicentre prospective cohort study, we found that plasma levels of sLOX-1 are markedly elevated in patients presenting with acute coronary syndromes (ACS) when compared with both chronic coronary syndrome (CCS) and healthy subjects (CTRL). High sLOX-1 levels were independently associated with a higher multivariable-adjusted 1-year mortality risk following ACS, a finding that remained consistent after controlling for GRACE 2.0. In patients subjected to serial intravascular ultrasound following the index ACS, sLOX-1 dropped markedly in those with coronary plaque regression, while persistently high sLOX-1 levels were associated with plaque progression. Full study results are available at The European Heart Journal.

_{Figure legend: §Adjusted for sex, age, ACS type, hs-CRP, history of hypercholesterolaemia, eGFR, LDL-C, and diagnosis of diabetes; †adjusted for sex, age, ACS type, hs-CRP, history of hypercholesterolaemia, eGFR, LDL-C, diagnosis of diabetes, NT-proBNP, and hs-TnT. ADAM, a disintegrin and metalloproteinase; GRACE, Global Registry of Acute Coronary Events; IVUS, intravascular ultrasound; MMP, matrix metalloproteinase; LOX-1, lectin-like oxidized low-density lipoprotein receptor-1; sLOX-1, soluble LOX-1.}