Targeting Rho-associated coiled-coil forming protein kinase (ROCK) in cardiovascular fibrosis and stiffening

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Pharmacology

Background:

• Pathological cardiac fibrosis and vascular stiffening are key contributors to cardiovascular diseases like heart failure, arrhythmias, and hypertension.
• These conditions arise from excessive extracellular matrix deposition and altered vascular mechanics.
• Rho-associated coiled-coil containing protein kinase (ROCK) is implicated in regulating pro-fibrotic and pro-stiffening signaling pathways.

Purpose of the Study:

• To outline the molecular mechanisms by which ROCK mediates fibrosis and stiffening in various cardiovascular cell types.
• To explore the potential of targeting ROCK for therapeutic intervention in cardiovascular fibrosis and stiffening.
• To highlight critical knowledge gaps and future research directions for ROCK inhibitor development.

Main Methods:

• Review of existing literature on ROCK signaling in cardiovascular cells.
• Analysis of molecular mechanisms underlying ROCK's role in fibroblast, immune cell, endothelial cell, and smooth muscle cell function.
• Speculative discussion on therapeutic targeting strategies for ROCK.

Main Results:

• ROCK signaling pathways are involved in mediating fibrosis and stiffening across multiple cardiovascular cell types, including fibroblasts, T helper cells, endothelial cells, vascular smooth muscle cells, and macrophages.
• ROCK's complex role suggests isoform- and tissue-specific functions in fibrosis.
• Potential therapeutic strategies targeting ROCK are proposed.

Conclusions:

• ROCK plays a significant role in cardiovascular fibrosis and stiffening through diverse cellular mechanisms.
• Further research is needed to elucidate isoform- and tissue-specific roles of ROCK.
• Targeting ROCK, particularly with isoform-specific inhibitors, holds promise for treating cardiovascular diseases, but requires addressing current knowledge gaps.