Entry #: 20
Date: 22 October 2017
Section: Acute inflammation
Topic: Oleacein and carotid plaque stabilization
Type: Ex vivo study
OliveNetTM Journal Club
Expert review of literature related to olives and olive oil
D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis
Oleacein may inhibit destabilization of carotid plaques from hypertensive patients. Impact on high mobility group protein-1
Filipek et al
Citation / Year
(1) / 2017
Oleacein, carotid plaque, carotid endarterectomy, high mobility group protein-1, tissue factor, matrix metalloproteinases, heme oxygenase 1
Previous study from this group indicating that the secoiridoid, oleacin from Oleaeuropaea (found mainly in the fruit paste and extra virgin olive oil), may have beneficial effects in cardiovascular diseases. Specifically, numerous cellular and molecular mechanisms had been identified including that oleacein: 1) reduces LDL oxidation, 2) inhibits myeloperoxidase levels, 3) down-regulates the expression of immune- and endothelial-cell associated adhesion molecules, 4) mediates a reduction in angiotensin II, and 5) interacts with erythrocyte cell membranes (2, 3). Further, studies indicated oleacein could form a complex with and increase absorption of haemoglobin-haptoglobin by CD136-expressing macrophages (4). This is relevant in context of atherosclerosis given the importance of CD136 in haemorrhage-induced plaque destabilization (5). Indeed, a switch from the M-1 (pro-inflammatory) to the M-2 anti-inflammatory macrophage phenotype due to increased interleukin-10 is observed (6). In this study, the authors extended the understanding of anti-inflammatory and antioxidant effects of oleacein by investigating the effect of the secoiridoid on lipopolysaccharide (LPS)-induced carotid plaque destabilization ex vivo. Briefly, carotid plaques were harvested during endarterectomy from hypertensive patients (n=20; M=nine, female=11), that had suffered transient ischemic attacks (lasting <24 hours). Within three hours following surgery, plaques were stimulated (1 μg/mL LPS) and treated with either oleacein (5, 10 and 20 μM), oleuropein (20 μM, negative control), and simvastatin (40 mg/mL, positive control), for 24 hours prior to analysis of supernatants.
Key points and implications
Commercially available enzyme-linked immunosorbent assays were used to measure the release of six key atherosclerosis-related proteins in the harvested supernatants. The findings indicated that compared to stimulated controls, oleacein decreased the release of: 1) high-mobility group protein B1 by >80% (marker of cell ischemia and damage), 2) tissue factor by >90% at 20 μM (activator of coagulation cascade), 3) matrix metalloproteinase-9 (MMP-9) by ~80% at 20 μM (overexpression associated with plaque instability) and 4) MMP-9/neutrophil gelatinase-associated lipocalin by 100% at 10 and 20 μM (complex prevents degradation of MMP-9 and represents a novel biomarker of atherosclerosis). Further, the findings indicated that compared to stimulated control, oleacein increased the release of: 1) interleukin-10 by >90% at 20 μM (anti-inflammatory cytokine), and 2) heme oxygenase-1 significantly at 10 and 20 μM (key antioxidant enzyme). Importantly, positive simvastatin controls behaved according expectation and negative oleuropein controls exhibited little effect on the release of the six proteins measured, as anticipated. Overall, these findings highlight the ability of oleacein to potentially prevent carotid plaque destabilization and may suggest preventative effects from in ischemic stroke. As suggested by the authors, consumption of 100 – 150 mL (based on levels of oleacein in typical extra-virgin olive oil), which has not been heated to >60˚C (oleacein decomposes above these temperatures), is required to achieve adequate blood levels of the secoiridoid. Given the relatively high levels required, the authors suggest industrial process to isolate the compound from common privet leaves (Ligustrum vulgare L., Oleaceae), which contain oleacein.
- A. Filipek, M. E. Czerwinska, A. K. Kiss, J. A. Polanski, M. Naruszewicz, Oleacein may inhibit destabilization of carotid plaques from hypertensive patients. Impact on high mobility group protein-1. Phytomedicine : international journal of phytotherapy and phytopharmacology 32, 68-73 (2017).
- M. Naruszewicz, M. E. Czerwinska, A. K. Kiss, Oleacein. translation from Mediterranean diet to potential antiatherosclerotic drug. Current pharmaceutical design 21, 1205-1212 (2015).
- F. Paiva-Martins et al., Powerful protective role of 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde against erythrocyte oxidative-induced hemolysis. Journal of agricultural and food chemistry 58, 135-140 (2010).
- A. Filipek, M. E. Czerwinska, A. K. Kiss, M. Wrzosek, M. Naruszewicz, Oleacein enhances anti-inflammatory activity of human macrophages by increasing CD163 receptor expression. Phytomedicine : international journal of phytotherapy and phytopharmacology 22, 1255-1261 (2015).
- A. V. Finn et al., Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. Journal of the American College of Cardiology 59, 166-177 (2012).
- F. O. Martinez, S. Gordon, The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000prime reports 6, 13 (2014).