Key result
Aged male LV vesicles promote in vitro fibrosis, while young and female vesicles protect via miRNAs.
Why the study?
Rates of cardiac fibrosis differ between young and aged individuals as well as men and women, but the role of matrix-bound extracellular vesicles across these groups is unclear.
Do age and sex-dependent differences in human cardiac matrix-bound exosomes modulate fibrosis?
Do age and sex-dependent differences in human cardiac matrix-bound exosomes modulate fibrosis?
Matrix-bound extracellular vesicles from human left ventricles show age- and sex-dependent differences in modulating fibrosis, suggesting a mechanism for differential clinical responses to myocardial infarction.
May inform age- and sex-specific post-MI fibrosis risk; leaves open human vesicle validation before clinical translation.
Aging is a risk factor for cardiovascular disease, the leading cause of death worldwide. Cardiac fibrosis is a harmful result of repeated myocardial infarction that increases risk of morbidity and future injury. Interestingly, rates of cardiac fibrosis are different between young and aged individuals, as well as men and women. Here, for the first time, we identify and isolate matrix-bound extracellular vesicles from the left ventricles (LVs) of young or aged men and women. These LV vesicles (LVVs) show differences in morphology and content between these four cohorts. LVVs effects on fibrosis were also investigated in vitro , and it was shown that aged male LVVs were pro-fibrotic, while other LVVs were anti-fibrotic. miRNAs identified from these LVVs could partially recapitulate these effects together, but not individually, and confer other benefits. These data suggest that synergistic effects of matrix-resident exosomal miRNAs may influence the differential clinical response to MI.
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Ronan et al. (2022) studied Cardiac fibrosis. Matrix-bound extracellular vesicles (LVVs) and miRNAs vs. Comparison between young/aged and male/female LVVs was evaluated on Effects on fibrosis in vitro. Aged male left ventricular matrix-bound vesicles were pro-fibrotic in vitro, while vesicles from young or female cohorts were anti-fibrotic, driven by synergistic miRNA effects.
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