Small size apolipoprotein(a) isoforms enhance inflammatory and proteolytic potential of collagen-primed monocytes

• Published in: Lipids in health and disease 2019-08, Vol.18 (1), p.166-7, Article 166
• Main Authors: Sabbah, Nadia, Jaisson, Stéphane, Garnotel, Roselyne, Anglés-Cano, Eduardo, Gillery, Philippe
• Format: Article
• Language: English
• Subjects: Aminocaproic Acid - pharmacology; Animals; Apolipoprotein(a); Apolipoproteins; Apolipoproteins A - biosynthesis; Apolipoproteins A - chemistry; Apolipoproteins A - pharmacology; Arteriosclerosis; Atherosclerosis; Binding sites; Blood & organ donations; Carboxypeptidase B; Cardiovascular disease; Care and treatment; Cell activation; Cellular Biology; Collagen; Collagen (type I); Collagen Type I - pharmacology; Complications and side effects; Coronary artery disease; Coronary heart disease; Coronary vessels; Endocrinology; Endocrinology and metabolism; Fibronectins - pharmacology; Gelatinase B; Heart attacks; Heart diseases; HEK293 Cells; Hematology; Human health and pathology; Humans; Immunology; Inflammation; Innate immunity; Isoforms; Laboratories; Life Sciences; Lipoprotein A; Lipoproteins; Lysine; Matrix metalloproteinase; Matrix Metalloproteinase 9 - biosynthesis; Metabolic disorders; Metalloproteinase; Molecular Weight; Monocytes; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Plasminogen - pharmacology; Population; Primary Cell Culture; Protein Binding; Protein Isoforms - biosynthesis; Protein Isoforms - chemistry; Protein Isoforms - pharmacology; Proteolysis; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Recombinant Proteins - pharmacology; Risk factors; Studies; Subcellular Processes
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-019-1106-4

Atherosclerosis is an inflammatory process involving activation of monocytes recruited by various chemoattractant factors, among which lipoprotein(a) and its specific apolipoprotein apo(a). Lp(a) contains a specific apolipoprotein apo(a) which size is determined by a variable number of repeats of a specific structural domain, the kringle IV type 2 (IV-2). Lp(a) plasma concentration and apo(a) size is inversely correlated, and smaller apo(a) are major risk factors for coronary heart disease. The aim of this study was to evaluate the effect of recombinant apo(a) isoforms (containing 10, 18 or 34 kringles) on monocytes interacting with type I collagen. Apo(a) isoforms stimulated reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) production by monocytes, and not modified monocytes adhesion on type I collagen. This effect was specific of apo(a) since no effect was observed in the presence of plasminogen and was inversely related to apo(a) size. The lysine analogue 6-aminohexanoic acid which blocks the lysine binding sites (LBS), and carboxypeptidase B (CpB) which cleaves carboxy-terminal lysine residues, abolished apo(a)-induced ROS and MMP-9 production, highlighting an effect mediated by apo(a) lysing-binding sites. These results indicate that activation of collagen-primed monocytes stimulated with apo(a) is a Kringle number-dependent effect and reinforce the hypothesis of a role for small size apo(a) isoforms in atherothrombosis.