Acute coronary syndrome remodels the protein cargo and functions of high-density lipoprotein subfractions
Ying Tan1, Ting Rong Liu1, Shui Wang Hu2
1Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Insights
High-density lipoprotein (HDL) subfractions become dysfunctional in acute coronary syndrome (ACS), with altered protein cargo contributing to impaired function. This shift impacts cardiovascular health.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Proteomics
Background:
- High-density lipoprotein (HDL) plays a crucial role in reverse cholesterol transport.
- HDL exists in subfractions, HDL2 and HDL3, with distinct functional properties.
- Acute coronary syndrome (ACS) is associated with altered HDL functionality.
Purpose of the Study:
- To investigate functional and proteomic changes in HDL subfractions (HDL2 and HDL3) in patients with ACS.
- To compare HDL subfractions from ACS patients with those from healthy controls.
Main Methods:
- Isolation of HDL2 and HDL3 subfractions from ACS patients and controls.
- Measurement of cholesterol efflux capacity, inflammatory index (HII), paraoxonase-1 (PON1) activity, and lipid hydroperoxide (LOOH) levels.
- Proteomic analysis to identify changes in protein composition of HDL subfractions.
Main Results:
- ACS patients exhibited increased HII and LOOH, and decreased PON1 activity and cholesterol efflux capacity in both HDL2 and HDL3 compared to controls.
- Proteomic analysis revealed significant alterations in protein cargo within HDL subfractions of ACS patients, including enrichment of nine proteins and decreased Rab-7b in HDL3, and altered protein levels in HDL2.
Conclusions:
- HDL subfractions shift towards a dysfunctional phenotype in ACS.
- The functional impairment of HDL in ACS is associated with significant remodeling of its protein cargo.
Objectives:
This study examined alterations in the functions and proteome of high-density lipoprotein (HDL) subfractions (HDL2 and HDL3) isolated from patients with acute coronary syndrome (ACS) compared with control subjects.
Methods:
We measured HDL subfraction cholesterol efflux capacity, inflammatory index (HII), paraoxonase-1 (PON1) activity, and lipid hydroperoxide (LOOH) levels in both male age-matched controls and the ACS group (n = 40/group). Additionally, proteomic analysis was used to monitor changes in the HDL subfraction proteome between controls and ACS subjects.
Results:
Both HDL2 and HDL3 from ACS patients had greater HII and LOOH levels compared with controls (P<0.001); PON1 activity and cholesterol efflux capacity in both HDL2 and HDL3 from the ACS group were significantly less than those of controls (P<0.001). Using proteomic analysis, we demonstrated that, compared with the control group, nine proteins were selectively enriched in HDL3 from subjects with ACS, and ras-related protein Rab-7b was decreased in HDL3. Additionally, in the ACS subjects, 12 proteins were decreased in HDL2 and 4 proteins were increased in HDL2.
Conclusions:
Functional HDL subfractions shifted to dysfunctional HDL subfractions during ACS, and the functional impairment was linked to remodeled protein cargo in HDL subfractions from ACS patients.
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