Recognition functions of pentameric C-reactive protein in cardiovascular disease

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Medicine

Background:

• C-reactive protein (CRP) plays a dual role in cardiovascular disease through its phosphocholine (PCh)-binding and low-density lipoprotein (LDL)-binding functions.
• Native pentameric CRP recognizes PCh on damaged cells, activating complement and exacerbating injury in conditions like myocardial infarction.
• Nonnative pentameric CRP interacts with LDL, potentially offering atheroprotective effects by modulating macrophage foam cell formation and LDL oxidation.

Purpose of the Study:

• To elucidate the distinct roles of native and nonnative C-reactive protein conformations in cardiovascular disease pathogenesis.
• To explore therapeutic strategies targeting CRP functions for treating atherosclerosis and myocardial infarction.

Main Methods:

• The study reviews existing literature and experimental data on CRP's interactions with PCh and LDL.
• Analysis of CRP's effects on complement activation, cellular damage, and atherogenic processes.

Main Results:

• CRP's PCh-binding function is detrimental in cardiovascular injury, worsening myocardial infarction and ischemia/reperfusion.
• CRP's nonnative conformation exhibits beneficial effects against atherosclerosis by interacting with LDL.
• Experimental data suggest atheroprotective properties of nonnative CRP.

Conclusions:

• Targeting CRP offers a potential therapeutic avenue for cardiovascular diseases.
• Temporarily inhibiting CRP's PCh-binding function and promoting its nonnative conformation may be a promising strategy.
• Complete suppression of CRP biosynthesis is unnecessary; modulation of its functions is key.