TY - JOUR
T1 - Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Adults
AU - Karlin, Hannah
AU - Sooda, Meera
AU - Larson, Martin
AU - Rong, Jian
AU - Huan, Tianxiao
AU - Mens, Michelle M J
AU - van Rooij, Frank J A
AU - Ikram, M Arfan
AU - Courchesne, Paul
AU - Freedman, Jane E
AU - Joehanes, Roby
AU - Mueller, Gregory P
AU - Kavousi, Maryam
AU - Ghanbari, Mohsen
AU - Levy, Daniel
N1 - Publisher Copyright: © 2024 The Authors.
PY - 2025
Y1 - 2025
N2 - BACKGROUND: Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level.METHODS AND RESULTS: Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with 8 CVD risk factors. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. Replication was carried out in 1999 RS (Rotterdam Study) participants. Pathway enrichment analyses were conducted and target genes were predicted for miRNAs associated with ≥5 risk factors in the FHS. In the FHS, 6 miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, and miR-193a-5p) were associated with ≥5 risk factors. This miRNA signature was enriched for pathways associated with CVD and several genes annotated to these pathways were predicted targets of the identified miRNAs. Furthermore, miR-193b-3p, miR-194-5p, and miR-193a-5p were each associated with ≥2 risk factors in the RS. Prospective analysis revealed 8 miRNAs associated with all-cause mortality in the FHS.CONCLUSIONS: These findings highlight associations between miRNAs and CVD risk factors that may provide valuable insights into the underlying pathogenesis of CVD.
AB - BACKGROUND: Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level.METHODS AND RESULTS: Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with 8 CVD risk factors. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. Replication was carried out in 1999 RS (Rotterdam Study) participants. Pathway enrichment analyses were conducted and target genes were predicted for miRNAs associated with ≥5 risk factors in the FHS. In the FHS, 6 miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, and miR-193a-5p) were associated with ≥5 risk factors. This miRNA signature was enriched for pathways associated with CVD and several genes annotated to these pathways were predicted targets of the identified miRNAs. Furthermore, miR-193b-3p, miR-194-5p, and miR-193a-5p were each associated with ≥2 risk factors in the RS. Prospective analysis revealed 8 miRNAs associated with all-cause mortality in the FHS.CONCLUSIONS: These findings highlight associations between miRNAs and CVD risk factors that may provide valuable insights into the underlying pathogenesis of CVD.
U2 - 10.1161/jaha.123.033674
DO - 10.1161/jaha.123.033674
M3 - Article
C2 - 38860398
SN - 2047-9980
VL - 13
SP - e033674
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 12
M1 - e033674
ER -
