Insulin-like growth factor-1 directly affects cardiac cellular remodelling via distinct pathways

Area of Science:

• Cardiovascular Research
• Cellular Signaling
• Pharmacology

Background:

• Insulin-like growth factor 1 (IGF-1) shows promise for cardiovascular diseases but has conflicting outcomes.
• Elevated IGF-1 is linked to poor prognosis in heart failure and offers no benefit in percutaneous coronary intervention.
• While PI3K/Akt and ERK1/2 pathways are known to be cardioprotective, other IGF-1 cellular mechanisms remain under-investigated.

Purpose of the Study:

• To investigate the cellular mechanisms of IGF-1 in cardiac myocytes and fibroblasts.
• To determine the role of ROCK, ASK-1, and p38MAPK pathways in IGF-1-induced cardiac effects.
• To explore potential therapeutic strategies for optimizing IGF-1 treatment in cardiovascular conditions.

Main Methods:

• Neonatal rat cardiac myocytes (NCMs) and fibroblasts (NCFs) were isolated and treated with IGF-1.
• Cells were pre-treated with inhibitors for PI3K/Akt, ERK1/2, ROCK, ASK-1, and p38MAPK pathways.
• Cardiac myocyte hypertrophy and fibroblast collagen synthesis were quantified using radiolabeled amino acid incorporation.

Main Results:

• IGF-1 dose-dependently increased NCM hypertrophy and NCF collagen synthesis.
• IGF-1-induced hypertrophy and collagen synthesis were significantly inhibited by IGFBP6 and all tested kinase inhibitors.
• This study identified ROCK, ASK-1, and p38MAPK as novel pathways activated by IGF-1 in cardiac cells.

Conclusions:

• IGF-1 activates ROCK, ASK-1, and p38MAPK pathways in cardiac myocytes and fibroblasts.
• The PI3K/Akt and ERK1/2 pathways may contribute to IGF-1-induced collagen synthesis.
• Targeting ROCK, ASK-1, and p38MAPK pathways with biased agonists could enhance cardioprotective benefits and reduce risks of IGF-1 therapy.