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Bioactive lipids improve serum HDL and PON1 activities in coronary artery disease patients: Ex-vivo study
Ali Khattib1, Manar Shmet2, Achinoam Levi2
1Natural Products and Analytical Chemistry Laboratory, MIGAL-Galilee Research Institute, Kiryat Shmona, Israel; Department of Biotechnology, Tel-Hai College, Upper Galilee, Israel; Technion Israel Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Insights
Bioactive lipids lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS) and oleoyl amide-MHS improved high-density lipoprotein (HDL) function and paraoxonase 1 (PON1) activity in patients with coronary artery disease (CAD). These findings suggest potential for these lipids to combat atherosclerosis.
Area of Science:
- Biochemistry
- Cardiovascular Research
- Lipidomics
Background:
- Atherosclerotic cardiovascular disease (CVD), including coronary artery disease (CAD), is a major global health concern.
- Atherosclerosis involves lipid accumulation and oxidation in blood vessel walls.
- Dysfunctional high-density lipoprotein (HDL) and reduced paraoxonase 1 (PON1) activity are implicated in CAD pathogenesis.
Purpose of the Study:
- To investigate the impact of novel bioactive lipids, lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS) and oleoyl-N-trimethyl homoserine amide (oleoyl amide-MHS), on HDL functionality and PON1 activity.
- To assess these effects in serum from patients with existing coronary artery plaques.
Main Methods:
- Serum samples were analyzed from 40 patients undergoing coronary CT angiography (CCTA), divided into a CAD group (n=20) and a control group (n=20).
- HDL properties, PON1 activity, cholesterol efflux, and inflammatory markers were measured.
- CAD patient serum was incubated with lyso-DGTS and oleoyl amide-MHS to evaluate their effects.
Main Results:
- CAD patients exhibited lower PON1 and cholesterol efflux activities, and higher pro-inflammatory markers compared to controls.
- HDL from CAD patients showed increased levels of oxidizing lipids.
- Incubation with lyso-DGTS and oleoyl amide-MHS restored HDL's antiatherogenic properties, increasing PON1 activity, cholesterol efflux, and anti-inflammatory capacity.
Conclusions:
- The bioactive lipids lyso-DGTS and oleoyl amide-MHS demonstrate potential to attenuate atherosclerosis.
- These lipids may exert their protective effects by improving dysfunctional HDL properties and enhancing PON1 activity.
- Further in vivo studies are warranted to confirm the athero-protective effects of these lipids.
Background:
Atherosclerotic cardiovascular disease (CVD) remains a leading cause of vascular disease worldwide. Atherosclerosis is characterized by the accumulation of lipids and oxidized lipids on the blood vessel walls. Coronary artery disease (CAD) is the most common display of atherosclerotic CVD.
Objectives:
We investigated the effects of the bioactive lipids as lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS (20,5,0)) and its derivative oleoyl-N-trimethyl homoserine amide (oleoyl amide-MHS) on the properties and functionality of HDL and paraoxonase 1 (PON1) activities in the serum of individuals who exhibited arterial plaque as observed by coronary CT angiography (CCTA).
Methods:
The study included two independent groups comprising 40 patients who had undergone arterial CCTA scans at Ziv Medical Center for various medical indications. The CAD group included 20 patients with coronary artery plaques with luminal stenosis of more than 50 % in a major coronary vessel. The control group consisted of 20 healthy patients (patients without artery plaques).
Results:
Serum samples from CAD patients exhibited lower serum PON1 and cholesterol efflux activities and higher pro-inflammatory than the control group. HDL isolated from CAD patients contains elevated levels of oxidizing lipids (specifically lyso- phosphatidyl ethanolamines and lyso-phosphocholines(compared to the control. However, incubation of the CAD patients' serum with lyso-DGTS and oleoyl amide-MHS restored the antiatherogenic activities of HDL. The lipids increased serum PON1 activities, enhanced apoB-depleted serum cholesterol-efflux activity, and elevated the serum's anti-inflammatory properties.
Conclusions:
The results of the present study suggest the potential of the bioactive lipids lyso-DGTS and oleoyl amide-MHS to attenuate atherosclerosis via the improvement of dysfunctional HDL properties and PON1 activities. Further, in-vivo experiments are needed to assess the athero-protective effect of the lipids.
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