Neighborhood socioeconomic deprivation and physical activity associate with extracellular vesicle size and cargo in a community-based cohort of women.

Figures

• 

  Fig. 1. EV size associates with Neighborhood Socioeconomic Deprivation (NSD) and Daily Step Count. (a) Representative EV size distribution profile and respective EV morphology using TEM negative staining TEM images were taken at 30,000x magnification (scale bar: 100 nm). (b) No association was found between size and concentration of plasma EVs isolated from 24 study participants. (c) Multivariable linear regression modeling of associations between measures of SDoH and EV concentration or size. Models are adjusted for ASCVD 10-yr risk score and BMI. Findings are displayed as standardized beta coefficients followed by the unadjusted p-value and the FDR adjusted p-value. Visual representation of the association between NSD and EV size (EV-z). (d) Multivariable linear regression modeling of associations between objective as well as self-reported measures of physical activity and EV concentration or size. Models are adjusted for ASCVD 10-yr risk score and BMI. Findings are displayed as standardized beta coefficient followed by the unadjusted p-value and the FDR adjusted p-value. Visual representation of the association between NSD and EV size (EV-z). (Significance is indicated by * and bold…

• 

  Fig. 2. miRNA content in EVs varies by EV size, NSD, and Daily Step count. From the initial cohort of 24 donors, we selected 12 donors who exhibited diverse profiles in terms of EV concentration, EV size, NSD, and daily step count. Donor selection was based on upper and lower quantiles (n = 6) of EV size ranking. We then analyzed the miRNA content within the EVs from these selected donors. Bivariate comparisons (Mann-Whitney test) of detected miRNAs by EV concentration (a/b), EV size (c/d), NSD (e/f), and Daily Step Count (g/h) are displayed. (Significance is indicated by * and with a p-value < 0.05, while ** indicates a p-value < 0.001; p-values indicate raw unadjusted p-values; error bar indicates standard error of mean. NSD=neighborhood socioeconomic deprivation)

• 

  Fig. 3. Bar graph of enriched pathways shown to be significantly impacted by the indicated miRNAs in an unbiased biostatistical analysis approach. The three miRNAs shown to be significantly different in EVs by either EV size, NSD, daily step count, or a combination of these factors are miR-1246 (a), miR-28-5p (b), and miR-765 (c). The x-axis indicates the enrichment ratio, while the y-axis indicates the signaling pathway identified.

• 

  Fig. 4. EV miR-28-5p expression is associated with increasing endothelial barrier function and decreasing EC migration. Human coronary artery endothelial cells (HCAECs) cultured on ECIS electrodes were treated with EVs isolated from human plasma. For the first 24 h of treatment, endothelial barrier function was measured. After 24 h of treatment, the monolayer was wounded utilizing the ECIS wounding module. Subsequently, the migration of HCAECs into the wounded area was measured. (a) Bivariate comparison of barrier function by EV concentration and size, NSD, and daily step count. (Mann Whitney test, n = 6 each group) (b) Correlation analysis of EV miRNA content to EC barrier function is plotted with the correlation coefficient and the p-value indicated. (n = 12, bold font indicates significance with a p-value < 0.05, significant p-values are further indicated by the *) (c) Bivariate comparison of migration by EV concentration and size as well as NSD and daily step count. (Mann Whitney test, n = 6 each group) (d) Correlation analysis of EV miRNA content to EC barrier function is plotted with the correlation coefficient and the p-value indicated. (n = 12, bold font indicates significance…