Signalling pathways in cardiac myocyte hypertrophy.

Area of Science:

• Cardiology
• Cell Biology
• Molecular Signaling

Background:

• Mammalian cardiac myocytes increase contractile power through hypertrophy, a process of cell enlargement without cell division.
• This hypertrophic response can be experimentally induced in cultured myocytes using alpha-adrenergic agonists or endothelin-1.
• Reversible protein phosphorylation and dephosphorylation are implicated in the signaling pathways governing hypertrophic growth.

Purpose of the Study:

• To review the evidence for and against the involvement of specific signaling proteins in myocyte hypertrophy.
• To highlight the roles of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) cascades, and calcineurin in regulating cardiac myocyte growth.
• To emphasize the potential significance of the extracellular signal-regulated kinase (ERK) cascade in myocyte hypertrophy.

Main Methods:

• Review of existing scientific literature on cardiac myocyte hypertrophy and associated signaling pathways.
• Analysis of the roles of protein kinase C (PKC), MAPK cascades (ERK, JNK, p38-MAPK), and calcineurin.
• Discussion of how these pathways modulate gene transcription via nuclear transcription factors.

Main Results:

• PKC is involved in activating the ERK cascade but not significantly in JNK or p38-MAPK activation.
• Calcineurin activation is dependent on intracellular calcium ([Ca2+i]) and calmodulin.
• Evidence for and against the roles of these signaling proteins in myocyte hypertrophy is discussed.

Conclusions:

• Multiple signaling pathways, including PKC, MAPK cascades, and calcineurin, are potential regulators of cardiac myocyte hypertrophy.
• The ERK cascade, in particular, warrants greater consideration for its role in this adaptive cellular response.
• Understanding these pathways is critical for comprehending cardiac adaptation and disease.