Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin

FASEB J. 2006 Mar;20(3):559-61. doi: 10.1096/fj.05-4857fje. Epub 2006 Jan 10.


Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NFkappaB, as well as the NFkappaB-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminocaproic Acid / pharmacology
  • Angiostatins / pharmacology
  • Apolipoproteins A / metabolism
  • Aspirin / pharmacology
  • Atherosclerosis / physiopathology*
  • Cell Movement
  • Cells, Cultured / cytology
  • Cells, Cultured / drug effects
  • Chemotaxis, Leukocyte / physiology*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • Coronary Artery Disease / physiopathology
  • Coronary Vessels / chemistry
  • Coronary Vessels / pathology
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Female
  • Gene Expression Regulation
  • Homocysteine / pharmacology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipoprotein(a) / pharmacology
  • Lipoprotein(a) / physiology*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Macrophage-1 Antigen / chemistry
  • Macrophage-1 Antigen / physiology*
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / metabolism*
  • NF-kappa B / metabolism
  • Plasminogen / pharmacology
  • Protein Binding
  • Protein Structure, Tertiary
  • Transfection


  • Apolipoproteins A
  • Lipoprotein(a)
  • Lymphocyte Function-Associated Antigen-1
  • Macrophage-1 Antigen
  • NF-kappa B
  • Homocysteine
  • Intercellular Adhesion Molecule-1
  • Angiostatins
  • Plasminogen
  • Aspirin
  • Aminocaproic Acid