Background
Macrophage cholesterol efflux capacity has been identified as a predictor for cardiovascular disease. We assessed the relationship between adipocyte-derived extracellular vesicle microRNAs and macrophage cholesterol efflux capacity.
Methods
We assessed an adolescent cohort (n = 93, Age, median (IQR) = 17 (3) year, Female = 71, Male = 22) throughout the BMI continuum (BMI = 45.2 (13.2) kg/m
2
) for: (1) cholesterol efflux capacity and lipoprotein profiles; (2) adipocyte-derived extracellular vesicle microRNAs in serum; (3) the role of visceral adipose tissue extracellular vesicle in regulation of cholesterol efflux and cholesterol efflux gene expression in THP-1 macrophages in vitro.
Results
Efflux capacity was significantly associated with HDL (r = 0.30, p = 0.01) and LDL (r = 0.33, p = 0.005) particle size. Multivariate-analysis identified six microRNAs associated (p < 0.05) with cholesterol efflux capacity: miR-3129-5p (Beta = 0.695), miR-20b (0.430), miR9-5p (0.111), miR-320d (− 0.190), miR301a-5p (0.042), miR-155-5p (0.004). In response to increasing concentrations (1 μg/mL vs. 3 μg/mL) of VAT extracellular vesicle, cholesterol efflux (66% ± 10% vs. 49% ± 2%; p < 0.01) and expression of ABCA1 (FC = 1.9 ± 0.8 vs 0.5 ± 0.2; p < 0.001), CD36 (0.7 ± 0.4 vs. 2.1 ± 0.8, p = 0.02), CYP27A1 (1.4 ± 0.4 vs. 0.9 ± 0.5; p < 0.05), and LXRA (1.8 ± 1.1 vs. 0.5 ± 0.2; p < 0.05) was altered in THP-1 cells in vitro.
Conclusion
Adipocyte-derived extracellular vesicle microRNAs may, in part, be involved macrophage cholesterol efflux regulation.
Electronic supplementary material
The online version of this article (10.1186/s12967-019-1980-6) contains supplementary material, which is available to authorized users.
Introduction:
LFLG severe AS (stroke volume index <35 mL/m2 or cardiac index <3.0 L/min/m2 and transvalvular aortic gradient <40 mmHg) is associated with worse clinical outcomes following surgical aortic valve replacement. However, there is paucity of data regarding impact of low left ventricular flow and transvalvular gradient on outcomes following TAVR. We evaluated the impact of baseline LFLG on outcomes following TAVR in patients with severe AS at our institution.
Hypothesis:
Patients with LFLG severe AS undergoing TAVR will have a higher rate of adverse clinical outcomes.
Methods:
In a retrospective single center registry, we analyzed the clinical, 2D doppler-echocardiographic and outcome data in consecutive patients who underwent TAVR with the Edwards Sapien transcatheter aortic valve for symptomatic severe AS at our tertiary care hospital from March 2012 to April 2014. Patients with LFLG were compared to non-LFLG patients. Background medical data, clinical endpoints (defined by the Valve Academic Research Consortium-2), length of stay (LOS), readmissions and mortality, were compared between the two groups. Wilcoxon rank-sum and Fisher’s exact tests were used to evaluate the hypothesis.
Results:
LFLG was found in 66 (32%) out of 206 patients. Baseline characteristics were comparable between the LFLG and non-LFLG group, except significant difference in STS scores (12.1±8 vs. 9.9±8, p=0.011), prior aortic valve surgery (16.7% vs. 6.4%, p=0.041) and atrial fibrillation/flutter (57.6% vs. 29.3% (p<0.001). Overall, peri-procedural complications were similar between both groups, however, LFLG patients required: longer ICU monitoring (113.8±175 vs. 67.3±97 hours, p=0.01), longer hospital LOS (14.2±11.7 vs. 10.5±7.7 days, p=0.032). These patients had a non-significant trend toward 30 day mortality (7.6 vs. 4.3%, p=0.335) but a significantly higher 1-year all-cause mortality (19.7% vs. 9.3% p=0.044).
Conclusions:
LFLG patients had higher co-morbidities but comparable peri-procedural complications and short-term mortality. However this group was associated with longer hospitalizations and higher 1-year all-cause-mortality following TAVR. Further studies are needed to fully define outcomes in LFLG patients.
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