Mast cell chymase, a chymotrypsin-like neutral protease, can proteolyze HDL 3. Here we studied the ability of rat and human chymase to proteolyze discoidal preβ-migrating reconstituted HDL particles (rHDLs) containing either apolipoprotein A-I (apoA-I) or apoA-II. Both chymases cleaved apoA-I in rHDL at identical sites, either at the N-terminus (Tyr 18 or Phe 33) or at the C-terminus (Phe 225), so generating three major truncated polypeptides that remained bound to the rHDL. The cleavage sites were independent of the size of the rHDL particles, but small particles were more susceptible to degradation than bigger ones. Chymase-induced truncation of apoA-I yielded functionally compromised rHDL with reduced ability to promote cellular cholesterol efflux. In sharp contrast to apoA-I, apoA-II was resistant to degradation. However, when apoA-II was present in rHDL that also contained apoA-I, it was degraded by chymase. We conclude that chymase reduces the ability of apoA-I in discoidal rHDL particles to induce cholesterol efflux by cleaving off either its amino- or carboxy-terminal portion. This observation supports the concept that limited extracellular proteolysis of apoA-I is one pathophysiologic mechanism leading to the generation and maintenance of foam cells in atherosclerotic lesions.

Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux / M. Lee, P.T. Kovanen, G. Tedeschi, E. Oungre, G. Franceschini, L. Calabresi. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 44:3(2003), pp. 539-546.

Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux

G. Tedeschi;G. Franceschini
Penultimo
;
L. Calabresi
Ultimo
2003

Abstract

Mast cell chymase, a chymotrypsin-like neutral protease, can proteolyze HDL 3. Here we studied the ability of rat and human chymase to proteolyze discoidal preβ-migrating reconstituted HDL particles (rHDLs) containing either apolipoprotein A-I (apoA-I) or apoA-II. Both chymases cleaved apoA-I in rHDL at identical sites, either at the N-terminus (Tyr 18 or Phe 33) or at the C-terminus (Phe 225), so generating three major truncated polypeptides that remained bound to the rHDL. The cleavage sites were independent of the size of the rHDL particles, but small particles were more susceptible to degradation than bigger ones. Chymase-induced truncation of apoA-I yielded functionally compromised rHDL with reduced ability to promote cellular cholesterol efflux. In sharp contrast to apoA-I, apoA-II was resistant to degradation. However, when apoA-II was present in rHDL that also contained apoA-I, it was degraded by chymase. We conclude that chymase reduces the ability of apoA-I in discoidal rHDL particles to induce cholesterol efflux by cleaving off either its amino- or carboxy-terminal portion. This observation supports the concept that limited extracellular proteolysis of apoA-I is one pathophysiologic mechanism leading to the generation and maintenance of foam cells in atherosclerotic lesions.
Settore BIO/10 - Biochimica
Settore BIO/14 - Farmacologia
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/11273
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 41
  • ???jsp.display-item.citation.isi??? 40
social impact