Background:
Prospective cohort studies and meta-analyses examining the relationship between HDL-cholesterol (C) and stroke are discordant and question the value of HDL-C as a marker for stroke risk prediction. Other properties of HDL-C such as cholesterol efflux capacity (CEC) and proteome, are less studied.
Methods:
We investigated the changes in HDL CEC and proteome to determine if they are associated with improved stroke recovery. Plasma from age- and lipid profile-matched healthy controls (N = 35) and stroke patients were collected at 24 (early, N = 35) and 96 hour (late, N = 20) post stroke, and analyzed with three independent assays to measure macrophage-mediated, ABCA1 and ABCG1-specific sterol efflux, and HDL proteome. Stroke recovery was assessed at 3 months using the Modified Rankin Scores (MRS) and the NIH Stroke Scale (NIHSS).
Results:
Both macrophage- and ABCG1-mediated CEC were reduced by 50% (
P
<0.0001) and 20% (
P
<0.038) in early and late post stroke samples, respectively, compared to the control group. Patients who had comparable or increased CEC between the two-time points exhibited lower NIHSS and MRS indicating better recovery. Proteomic analysis of HDL indicated a distinct time-dependent remodeling post stroke. Coagulation complement cascade proteins (FGB, FGA, A2M, C3) significantly increased (FDR>0.01) early and returned to control levels later, inflammation proteins (SAA1, SAA2, PON1, C4B) increased early and continued to increase. Interestingly, platelet adhesion proteins (DSG1, JUP, ITGB1, ITGA2, TUBB, DNAH3, PF4) were abundantly present in only later samples.
Conclusion:
1) patients who maintain or improve HDL CEC post stroke exhibit better recovery scores, 2) post stroke HDL proteome remodeling is dynamic with distinct time-dependent protein signatures that may associate with stroke recovery.