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Circulating soluble LOX-1 and patient prognosis after an acute coronary syndrome

Schiopu, Alexandru LU orcid ; Svedlund, Sara ; Narasimhan, Gayathri LU ; Juin Loong, Bi LU ; Yndigegn, Troels LU ; Varma, Vijayalakshmi ; Ongstad, Emily L. ; Goncalves, Isabel LU orcid ; Collén, Anna and Nilsson, Jan LU , et al. (2025) In Heart
Abstract

Background: The lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) mediates atherosclerotic plaque inflammation and vulnerability. On activation, LOX-1 sheds its extracellular domain into the circulation as soluble LOX-1 (sLOX-1). sLOX-1 is markedly elevated in patients with acute coronary syndrome (ACS). Methods: We prospectively assessed the associations between plasma sLOX-1 and the development of heart failure (HF), major adverse cardiovascular events (MACE) and coronary and left ventricular (LV) dysfunction in two cohorts of patients with ACS. The first cohort comprised 524 patients recruited during the acute index event at the coronary care unit of Skåne University Hospital, Malmö, Sweden. The second cohort included... (More)

Background: The lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) mediates atherosclerotic plaque inflammation and vulnerability. On activation, LOX-1 sheds its extracellular domain into the circulation as soluble LOX-1 (sLOX-1). sLOX-1 is markedly elevated in patients with acute coronary syndrome (ACS). Methods: We prospectively assessed the associations between plasma sLOX-1 and the development of heart failure (HF), major adverse cardiovascular events (MACE) and coronary and left ventricular (LV) dysfunction in two cohorts of patients with ACS. The first cohort comprised 524 patients recruited during the acute index event at the coronary care unit of Skåne University Hospital, Malmö, Sweden. The second cohort included 363 patients with ACS treated with acute percutaneous intervention at Sahlgrenska University Hospital, Gothenburg, Sweden. Additionally, we examined the anti-inflammatory effects of LOX-1 blockade in vitro using human umbilical vein endothelial cells (HUVECs). Results: In the first cohort, acute-phase sLOX-1 was associated with incident HF and MACE independently of cardiovascular risk factors, revascularisation and medication (HR per 1-SD sLOX-1 increase: 1.57 (95% CI: 1.10 to 2.23; p=0.012) for HF and 1.36 (1.08 to 1.71; p=0.009) for MACE). Elevated sLOX-1 was also associated with lower LV ejection fraction and accelerated remodelling, as measured by echocardiography at 1-year post-ACS. In the second cohort, sLOX-1 was negatively associated with left anterior descending coronary artery flow reserve and LV systolic function, and positively correlated with soluble markers of systemic inflammation and cardiac overload at 4 and 16 weeks post-ACS. In vitro, antibody-mediated LOX-1 blockade prevented oxidised low-density lipoprotein-induced HUVEC activation. Conclusions: Elevated plasma sLOX-1 at baseline and during follow-up is associated with incident HF and MACE, as well as cardiac and coronary dysfunction in patients with ACS. As plasma sLOX-1 levels may reflect the intensity of LOX-1 expression on vascular and immune cells, these findings support LOX-1 as a potentially important therapeutic target to improve prognosis in patients with ACS.

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publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Acute Coronary Syndrome, Biomarkers, Cohort Studies, Heart failure, Inflammation
in
Heart
article number
heartjnl-2025-326315
publisher
BMJ Publishing Group
external identifiers
  • scopus:105016107765
ISSN
1355-6037
DOI
10.1136/heartjnl-2025-326315
language
English
LU publication?
yes
id
cd8f36e6-7690-4189-a748-004b7f52e842
date added to LUP
2025-11-11 15:44:16
date last changed
2025-11-11 15:45:12
@article{cd8f36e6-7690-4189-a748-004b7f52e842,
  abstract     = {{<p>Background: The lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) mediates atherosclerotic plaque inflammation and vulnerability. On activation, LOX-1 sheds its extracellular domain into the circulation as soluble LOX-1 (sLOX-1). sLOX-1 is markedly elevated in patients with acute coronary syndrome (ACS). Methods: We prospectively assessed the associations between plasma sLOX-1 and the development of heart failure (HF), major adverse cardiovascular events (MACE) and coronary and left ventricular (LV) dysfunction in two cohorts of patients with ACS. The first cohort comprised 524 patients recruited during the acute index event at the coronary care unit of Skåne University Hospital, Malmö, Sweden. The second cohort included 363 patients with ACS treated with acute percutaneous intervention at Sahlgrenska University Hospital, Gothenburg, Sweden. Additionally, we examined the anti-inflammatory effects of LOX-1 blockade in vitro using human umbilical vein endothelial cells (HUVECs). Results: In the first cohort, acute-phase sLOX-1 was associated with incident HF and MACE independently of cardiovascular risk factors, revascularisation and medication (HR per 1-SD sLOX-1 increase: 1.57 (95% CI: 1.10 to 2.23; p=0.012) for HF and 1.36 (1.08 to 1.71; p=0.009) for MACE). Elevated sLOX-1 was also associated with lower LV ejection fraction and accelerated remodelling, as measured by echocardiography at 1-year post-ACS. In the second cohort, sLOX-1 was negatively associated with left anterior descending coronary artery flow reserve and LV systolic function, and positively correlated with soluble markers of systemic inflammation and cardiac overload at 4 and 16 weeks post-ACS. In vitro, antibody-mediated LOX-1 blockade prevented oxidised low-density lipoprotein-induced HUVEC activation. Conclusions: Elevated plasma sLOX-1 at baseline and during follow-up is associated with incident HF and MACE, as well as cardiac and coronary dysfunction in patients with ACS. As plasma sLOX-1 levels may reflect the intensity of LOX-1 expression on vascular and immune cells, these findings support LOX-1 as a potentially important therapeutic target to improve prognosis in patients with ACS.</p>}},
  author       = {{Schiopu, Alexandru and Svedlund, Sara and Narasimhan, Gayathri and Juin Loong, Bi and Yndigegn, Troels and Varma, Vijayalakshmi and Ongstad, Emily L. and Goncalves, Isabel and Collén, Anna and Nilsson, Jan and Gan, Li Ming}},
  issn         = {{1355-6037}},
  keywords     = {{Acute Coronary Syndrome; Biomarkers; Cohort Studies; Heart failure; Inflammation}},
  language     = {{eng}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Heart}},
  title        = {{Circulating soluble LOX-1 and patient prognosis after an acute coronary syndrome}},
  url          = {{http://dx.doi.org/10.1136/heartjnl-2025-326315}},
  doi          = {{10.1136/heartjnl-2025-326315}},
  year         = {{2025}},
}