Heat shock protein-56 is induced by cardiotrophin-1 and mediates its hypertrophic effect

Area of Science:

• Cardiovascular Biology
• Molecular Cell Biology
• Cytokine Signaling

Background:

• Cardiotrophin-1 (CT-1), an IL-6 family cytokine, exhibits protective and hypertrophic effects on the heart.
• CT-1 upregulates heat shock proteins (HSPs) like hsp70 and hsp90, implicated in cellular protection.
• The role of other HSPs, such as hsp56 (FKBP59), in CT-1's cardiac effects remains unclear.

Purpose of the Study:

• To investigate the induction and functional role of heat shock protein 56 (hsp56) in CT-1-mediated cardiac hypertrophy.
• To determine if hsp56 contributes to the hypertrophic response in primary neonatal rat cardiac myocytes.

Main Methods:

• CT-1 treatment was used to assess hsp56 mRNA and protein expression in cardiac cells.
• Overexpression of hsp56 was achieved using plasmid and Herpes viral vectors in neonatal rat cardiac myocytes.
• Antisense constructs were employed to inhibit hsp56 expression and evaluate its impact on CT-1's hypertrophic effect.

Main Results:

• CT-1 treatment significantly increased both mRNA and protein levels of hsp56.
• Overexpression of hsp56 led to a marked increase in cardiac myocyte size and protein:DNA ratio.
• Hsp56 knockdown using antisense constructs blocked the hypertrophic effect of CT-1, while hsp27, hsp70, and hsp90 overexpression did not affect cell size.

Conclusions:

• Heat shock protein 56 (hsp56) is induced by Cardiotrophin-1 (CT-1) in cardiac cells.
• Hsp56 plays a critical role in mediating CT-1-induced cardiac hypertrophy, distinct from the protective roles of hsp70 and hsp90.
• This study identifies hsp56 as the first heat shock protein demonstrated to have a hypertrophic effect in cardiac myocytes.