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Rodosthenous, Rodosthenis

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Rodosthenous

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Rodosthenous, Rodosthenis
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    Ambient particulate matter and microRNAs in extracellular vesicles: a pilot study of older individuals
    (BioMed Central, 2016) Rodosthenous, Rodosthenis; Coull, Brent; Lu, Quan; Vokonas, Pantel S.; Schwartz, Joel; Baccarelli, Andrea
    Background: Air pollution from particulate matter (PM) has been linked to cardiovascular morbidity and mortality; however the underlying biological mechanisms remain to be uncovered. Gene regulation by microRNAs (miRNAs) that are transferred between cells by extracellular vesicles (EVs) may play an important role in PM-induced cardiovascular risk. This study sought to determine if ambient PM2.5 levels are associated with expression of EV-encapsulated miRNAs (evmiRNAs), and to investigate the participation of such evmiRNAs in pathways related to cardiovascular disease (CVD). Methods: We estimated the short- (1-day), intermediate- (1-week and 1-month) and long-term (3-month, 6-month, and 1-year) moving averages of ambient PM2.5 levels at participants’ addresses using a validated hybrid spatio-temporal land-use regression model. We collected 42 serum samples from 22 randomly selected participants in the Normative Aging Study cohort and screened for 800 miRNAs using the NanoString nCounter® platform. Mixed effects regression models, adjusted for potential confounders were used to assess the association between ambient PM2.5 levels and evmiRNAs. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways that are regulated by PM-associated evmiRNAs. Results: We found a significant association between long-term ambient PM2.5 exposures and levels of multiple evmiRNAs circulating in serum. In the 6-month window, ambient PM2.5 exposures were associated with increased levels of miR-126-3p (0.74 ± 0.21; p = 0.02), miR-19b-3p (0.52 ± 0.15; p = 0.02), miR-93-5p (0.78 ± 0.22; p = 0.02), miR-223-3p (0.74 ± 0.22; p = 0.02), and miR-142-3p (0.81 ± 0.21; p = 0.03). Similarly, in the 1-year window, ambient PM2.5 levels were associated with increased levels of miR-23a-3p (0.83 ± 0.23; p = 0.02), miR-150-5p (0.90 ± 0.24; p = 0.02), miR-15a-5p (0.70 ± 0.21; p = 0.02), miR-191-5p (1.20 ± 0.35; p = 0.02), and let-7a-5p (1.42 ± 0.39; p = 0.02). In silico pathway analysis on PM2.5-associated evmiRNAs identified several key CVD-related pathways including oxidative stress, inflammation, and atherosclerosis. Conclusions: We found an association between long-term ambient PM2.5 levels and increased levels of evmiRNAs circulating in serum. Further observational studies are warranted to confirm and extend these important findings in larger and more diverse populations, and experimental studies are needed to elucidate the exact roles of evmiRNAs in PM-induced CVD. Electronic supplementary material The online version of this article (doi:10.1186/s12989-016-0121-0) contains supplementary material, which is available to authorized users.
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    Extracellular Vesicles in Cardiovascular Theranostics
    (Ivyspring International Publisher, 2017) Bei, Yihua; Das, Saumya; Rodosthenous, Rodosthenis; Holvoet, Paul; Vanhaverbeke, Maarten; Monteiro, Marta Chagas; Monteiro, Valter Vinicius Silva; Radosinska, Jana; Bartekova, Monika; Jansen, Felix; Li, Qian; Rajasingh, Johnson; Xiao, Junjie
    Extracellular vesicles (EVs) are small bilayer lipid membrane vesicles that can be released by most cell types and detected in most body fluids. EVs exert key functions for intercellular communication via transferring their bioactive cargos to recipient cells or activating signaling pathways in target cells. Increasing evidence has shown the important regulatory effects of EVs in cardiovascular diseases (CVDs). EVs secreted by cardiomyocytes, endothelial cells, fibroblasts, and stem cells play essential roles in pathophysiological processes such as cardiac hypertrophy, cardiomyocyte survival and apoptosis, cardiac fibrosis, and angiogenesis in relation to CVDs. In this review, we will first outline the current knowledge about the physical characteristics, biological contents, and isolation methods of EVs. We will then focus on the functional roles of cardiovascular EVs and their pathophysiological effects in CVDs, as well as summarize the potential of EVs as therapeutic agents and biomarkers for CVDs. Finally, we will discuss the specific application of EVs as a novel drug delivery system and the utility of EVs in the field of regenerative medicine.
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    Publication
    Micrornas in Extracellular Vesicles as Novel Biomarkers in Environmental Epidemiology
    (2016-05-03) Rodosthenous, Rodosthenis; Baccarelli, Andrea A.; Coull, Brent A.; Lu, Quan; Wright, Robert O.
    Despite important achievements of Environmental Epidemiology in identifying major environmental health problems in recent years, little is known about the underlying biological mechanisms that link environmental exposures to certain outcomes. Recent discovery of extracellular vesicles (EVs) as a novel mechanism of cellular communication has opened new avenues for non-invasive access to subclinical molecular signals, which might help exposing such mechanisms. In this work, we evaluate the potential of microRNAs, molecular signals that are contained in EVs circulating in the blood, as biomarkers in two very important environmental health problems: (a) the causal association between air pollution and cardiovascular disease and (b) the association between prenatal lead exposure and impaired fetal growth. For this work, we used cutting-edge and high-throughput methods to isolate EVs from the blood of study participants, and profile their content in microRNAs (evmiRNAs). We further incorporated a broad array of sophisticated statistical methods to (a) determine the association of ambient particulate matter of <2.5μm diameter (PM2.5) and evmiRNAs (Chapter 1), (b) determine the association between prenatal lead exposure and fetal growth (Chapter 2), and (c) evaluate the potential of evmiRNAs as early biomarkers of fetal growth impairment (Chapter 3). The findings from Chapter 1 showed positive associations between long-term exposure to PM2.5 and levels of evmiRNAs in the blood circulation of older individuals, several of which were found to be enriched in biological pathways related to cardiovascular disease. Results from Chapter 2 showed a negative association between prenatal exposure to lead and birthweight-for-gestational age (BWGA), and revealed that the magnitude of the association is much bigger in the lower percentiles of the BWGA distribution. Finally, the findings from Chapter 3 suggested that levels of evmiRNAs provide a very promising opportunity for the development of minimally-invasive biomarkers to detect and monitor impaired fetal growth early in pregnancy. This work demonstrates the tremendous potential of evmiRNAs in the field of Environmental Epidemiology. EVs and their content provide an unprecedented, yet easily accessible source of molecular signals that can help us better understand the biological mechanisms involved in linking environmental exposures to certain outcomes.