Cardiotrophin-1 and urocortin cause protection by the same pathway and hypertrophy via distinct pathways in cardiac...

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cytokine Signaling

Background:

• Cardiotrophin-1 (CT-1), an Interleukin-6 family cytokine, exhibits hypertrophic and protective effects on cardiac cells.
• Both CT-1 and urocortin utilize the p42/44 mitogen-activated protein kinase (p42/44 MAPK) pathway for cardiac myocyte protection.

Purpose of the Study:

• To determine if urocortin induces cardiac myocyte hypertrophy.
• To investigate if urocortin shares signaling pathways with CT-1 for hypertrophy.
• To examine the effects of CT-1 and urocortin on both neonatal and adult cardiac myocytes.

Main Methods:

• Cultured neonatal and adult rat cardiac myocytes were treated with CT-1 and urocortin.
• Hypertrophy was assessed by measuring cell area and the protein:DNA ratio.
• Specific signaling pathways, including STAT3 and p42/44 MAPK, were inhibited to elucidate their roles.

Main Results:

• Both urocortin and CT-1 induced hypertrophy in both neonatal and adult cardiac myocytes.
• CT-1's hypertrophic effect involved the signal transducer and activator of transcription 3 (STAT3) pathway.
• Urocortin's hypertrophic effect was independent of the STAT3 pathway.
• Neither cytokine's hypertrophic effect was dependent on the p42/44 MAPK pathway.
• The protective effects of both cytokines were independent of the STAT3 pathway.

Conclusions:

• Urocortin is identified as a novel hypertrophic and protective agent for cardiac myocytes.
• Urocortin mediates hypertrophy through a distinct pathway compared to CT-1.
• Both CT-1 and urocortin share a common pathway for mediating protection in cardiac cells.