Utility of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) in the postmortem diagnosis of ischemic heart disease
Introduction
Ischemic heart disease (IHD) is a major cause of sudden death in developed countries. Biochemical markers are central to the clinical diagnosis of IHD. However, the usefulness of biochemical markers for the postmortem diagnosis of IHD in forensic autopsy cases is uncertain because of postmortem changes. In general, the autopsy diagnosis of IHD is achieved through both macroscopic and microscopic findings based on anamnesis, death-related details, or both. Because early-stage pathological consequences of IHD can only be observed 6 h after onset, the diagnosis of IHD in sudden death cases is challenging.1
Several biochemical markers, such as N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (hFABP), creatine kinase MB (CKMB), myoglobin, cardiac troponin (cTn) T, and cardiac myosin light chain I, are known to increase in patients with IHD.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Previous studies have measured the levels of these biochemical markers in forensic autopsy cases. Although some studies revealed a significant difference in serum cTnT, NT-proBNP, and hFABP levels and pericardial fluid myoglobin, CKMB, and cTnT levels, postmortem elevation of these markers was a major concern.17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29
Atherosclerosis plays a major role in the pathogenesis of IHD. Oxidized low-density lipoprotein (LDL) is associated with atherogenesis, and lectin-like oxidized LDL receptor-1 (LOX-1) is the endothelial receptor of oxidized LDL.30,31 LOX-1 is a type II membrane protein that belongs to the C-type lectin family and is overexpressed in the endothelial cells, macrophages, and smooth muscle cells of atherosclerotic lesions.30,31 LOX-1 overexpression in the atherosclerotic lesions in blood vessels releases, by a cleavage process, the extracellular domain of this receptor into the blood as soluble LOX-1 (sLOX-1).32,33 Tumor necrosis factor alpha-converting enzyme (TACE)/ADAM17, a disintegrin metalloproteinase domain-containing protein 10, and interleukin-18 are involved in this cleavage process,34, 35, 36 and sLOX-1 may be associated with plaque vulnerability. Recent studies have reported increased serum sLOX-1 levels in patients with acute coronary syndrome (ACS), suggesting that measurement of sLOX-1 may be useful in the clinical diagnosis of acute-phase IHD.37, 38, 39, 40, 41, 42, 43, 44 Other studies have revealed serum sLOX-1 elevation in patients with obesity, type II diabetes, atherosclerotic conditions, and aortic dissection.45, 46, 47
To the best of our knowledge, no studies have investigated the use of sLOX-1 in forensic autopsy cases. In the present study, we measured the level of sLOX-1 not only in serum, but also in pericardial fluid and urine because serum biomarkers are likely to be unstable owing to postmortem changes, and we validated their use in the postmortem diagnosis of IHD.
Section snippets
Case selection
The present study included forensic autopsies performed at the Jikei University School of Medicine, between January 2015 and March 2017. We examined 70 cases of acute IHD (mean age: 61.9 years; range: 35–87 years) and 79 control cases (mean age: 62.2 years; range: 22–89 years). The diagnosis of acute IHD was based on both macroscopic findings such as coronary stenosis and signs of abrupt death (blood fluidity, organ congestion), and microscopic findings such as coronary embolism/plaque rupture
Baseline characteristics
Table 2 shows the baseline characteristics of the acute IHD and control cases. No significant differences in age were found between the groups. Mean body mass index (BMI) and heart weight were significantly higher in acute IHD group compared to the control cases.
sLOX-1 levels between acute IHD and control cases
As shown in Table 3, we observed a significant increase in sLOX-1 levels in the pericardial fluid and urine of acute IHD cases compared to the control cases. The median levels of serum sLOX-1 in acute IHD and control cases were
Discussion
sLOX-1 is suggested to be associated with plaque vulnerability.38,39 Recent studies show serum sLOX-1 elevation in ACS.37, 38, 39, 40, 41, 42, 43, 44 Hayashida et al.37 discovered earlier peak value of serum sLOX-1 compared to TnT in ACS patients. Furthermore, the peak value of serum sLOX-1 in ACS patients were observed at the time of hospital arrival, suggesting that serum sLOX-1 levels may begin to rise before the onset of ACS.37 Kume et al.40 suggested that sLOX-1 elevation has a different
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