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Decreased HSP70 expression on serum exosomes contributes to cardiac fibrosis during senescence

hsp70 exosomes cardiac fibrosis senescence

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#1 Engadin

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Posted 16 May 2019 - 05:09 PM


Published at Rejuvenation Science News

 

 

OBJECTIVE:

 

Aging is now considered as an independent risk factor for cardiac fibrosis. However, the mechanisms underlying aging-related cardiac fibrosis remain unknown. Here, we examine the role of serum exosomes in this process.

 

MATERIALS AND METHODS:

 

Experiments were conducted using 6-week-old or 24-week-old male Sprague-Dawley (SD) rats. Cardiac sections were treated with Masson’s trichrome stain to evaluate fibrosis. Exosomes were isolated from the serum, characterized and quantified using Western blot, electron microscopy, and qNano analysis, and co-cultured with transforming growth factor-β1 (TGF-β1)-induced primary cardiac fibroblasts (CF). Co-cultures were also carried out in the presence of a hot shock protein 70 (HSP70) inhibitor (gefitinib) or inducer (geranylgeranylacetone) to evaluate the role of HSP70 in cardiac fibrosis.

 

RESULTS:

 

Cardiac fibrosis as well as serum exosomes levels were increased during senescence. We observed an increase in fibroblast proliferation and myofibroblast differentiation when CF were co-cultured with exosomes from old rats, compared to those from young mice. Observing a decrease in surface HSP70 expression on the exosomes derived from old rats, we tested the effects of HSP70 inhibition or overexpression on the CF co-cultures. HSP70 inhibition increased fibroblast proliferation and myofibroblast differentiation in CF co-cultures containing exosomes from the young rats, while HSP70 overexpression attenuated fibroblast proliferation and myofibroblast differentiation in CF co-cultures containing exosomes from the old rats.

 

CONCLUSIONS:

 

Using an animal model of cardiac fibrosis, we show a decrease in HSP70 expression on the exosomal surface with aging, which may contribute to cardiac fibrosis.

 

 

S O U R C E :   EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES

 







Also tagged with one or more of these keywords: hsp70, exosomes, cardiac fibrosis, senescence

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