High-density lipoprotein carbamylation and dysfunction in vascular disease

Area of Science:

• Cardiovascular Science
• Biochemistry
• Nephrology

Background:

• High-density lipoprotein (HDL) is recognized for its cardioprotective and anti-atherogenic functions.
• Despite efforts to optimize HDL cholesterol (HDL-C) levels, therapeutic success in reducing atherothrombotic burden remains limited.
• This highlights the need to investigate HDL function and dysfunction, particularly its susceptibility to modifications.

Purpose of the Study:

• To review the multifaceted functions of HDL and its susceptibility to modifications.
• To discuss the role of HDL carbamylation in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD).
• To explore the specific impact of HDL carbamylation in patients with chronic kidney disease (CKD).

Main Methods:

• Literature review summarizing HDL structure and function.
• Analysis of evidence linking protein modifications to HDL's atherogenic potential.
• Focus on carbamylation as a key post-translational modification affecting HDL.

Main Results:

• HDL exerts cardioprotective effects through its complex lipid and proteome interactions.
• Carbamylation, an irreversible protein modification, significantly alters HDL function.
• Growing evidence implicates carbamylated HDL in the development and progression of ASCVD, notably in CKD.

Conclusions:

• Understanding HDL's functional modifications is critical for addressing cardiovascular disease.
• HDL carbamylation emerges as a significant factor in ASCVD, particularly in the context of CKD.
• Further research into HDL carbamylation may reveal novel therapeutic targets for cardiovascular protection.