Midkine: A multifaceted driver of atherosclerosis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Growth Factor Signaling

Background:

• Atherosclerosis underlies major cardiovascular events like heart attack and stroke.
• Midkine (MK) is a heparin-binding growth factor implicated in inflammatory and hypoxic conditions.
• Elevated circulating midkine levels are observed in hypertension, obesity, and peripheral artery disease.

Purpose of the Study:

• To review the structure, expression, and signaling pathways of midkine.
• To emphasize midkine's proatherogenic role in cardiovascular disease.
• To highlight midkine as a potential therapeutic target for atherosclerosis.

Main Methods:

• Literature review of midkine's role in atherosclerosis.
• Analysis of midkine's involvement in key atherogenic processes.
• Examination of midkine's impact on cellular pathways relevant to atherosclerosis.

Main Results:

• Midkine expression is upregulated under inflammatory and hypoxic conditions.
• Midkine activates signaling pathways regulating cell survival, migration, and oncogenesis.
• Midkine promotes atherosclerosis by influencing macrophage lipid accumulation, inflammation, neointima formation, insulin resistance, and apoptosis.

Conclusions:

• Midkine plays a significant proatherogenic role.
• Midkine influences multiple pathophysiological processes in atherogenesis.
• Midkine represents a promising therapeutic target for atherosclerosis and related conditions.