Elastin-elastases and inflamm-aging.

Abstract

Degradation of elastin, the main amorphous component of elastic fibers, by elastases belonging to the serine, metallo, or cysteine families leads to the generation of elastin fragments, designated as elastokines in keeping with their cytokine-like properties. Generation of elastokines from one of the longest lived protein in human might represent a strong tissue repair signal. Indeed, they (1) exhibit potent chemotactic activity for leukocytes, (2) stimulate fibroblast and smooth muscle cell proliferation, and (3) display proangiogenic activity as potent as VEGF. However, continuous exposure of cells to these matrikines, through increased elastase(s) expression with age, can contribute to the formation of a chronic inflammatory state, that is, inflamm-aging. Importantly, binding of elastokines to S-Gal, their cognate receptor, proved to stimulate matrix metalloproteinase expression in normal and cancer cells. Besides, these elastin fragments can polarize lymphocytes toward a Th-1 response or induce an osteogenic response in smooth muscle cells, and arterial wall calcification. In this chapter, emphasis will be made on the contribution of elastokines on the genesis of age-related arterial wall diseases, particularly abdominal aortic aneurysms (AAAs). An elastokine theory of AAAs progression will be proposed. Age is one main risk factor of cancer incidence and development. The myriad of biological effects exerted by elastokines on stromal and inflammatory cells led us to hypothesize that they might be main actors in elaborating a favorable cancerization field in melanoma; for instance these peptides could catalyze the vertical growth phase transition in melanoma through increased expression of gelatinase A and membrane-type 1 matrix metalloproteinase.

• Authors: Frank Antonicelli, Georges Bellon, Laurent Debelle, William Hornebeck
• Journal: Current topics in developmental biology (Curr Top Dev Biol) Vol. 79 Pg. 99-155 ( 2007) ISSN: 0070-2153 [Print] United States
• PMID: 17498549 (Publication Type: Journal Article, Review)

Chemical References

• Peptides
• Receptors, Cell Surface
• elastin-binding proteins
• Elastin
• Pancreatic Elastase
• Matrix Metalloproteinases

Topics

• Aging (physiology)
• Amino Acid Motifs
• Animals
• Arteries (metabolism, pathology)
• Disease Progression
• Elastic Tissue (metabolism, physiology)
• Elastin (genetics, metabolism)
• Humans
• Inflammation (metabolism)
• Matrix Metalloproteinases (genetics, metabolism)
• Melanoma (pathology, physiopathology)
• Neovascularization, Physiologic
• Pancreatic Elastase (genetics, metabolism)
• Peptides (genetics, metabolism)
• Receptors, Cell Surface (metabolism)
• Signal Transduction (physiology)
• T-Lymphocytes (physiology)
• Vascular Diseases (metabolism)