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HDL antielastase activity prevents smooth muscle cell anoikis, a potential new antiatherogenic property
Author(s) -
Ortiz-Muñoz Guadalupe,
Houard Xavier,
Martín-Ventura Jose-Luis,
Ishida Brian Y.,
Loyau Stephane,
Rossignol Patrick,
Moreno Juan-Antonio,
Kane John P.,
Chalkley Robert J.,
Burlingame Alma L.,
Michel Jean-Baptiste,
Meilhac Olivier
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-127928
Subject(s) - elastase , proteolysis , medicine , chemistry , elastin , apolipoprotein b , endocrinology , extracellular matrix , biochemistry , microbiology and biotechnology , biology , enzyme , cholesterol , genetics
Various studies using proteomic approaches have shown that HDL can carry many proteins other than its constitutive apolipoprotein A‐I (apoA‐I). Using mass spectrometry and Western blotting, we showed the presence of α 1 ‐antitrypsin (AAT) (SERPINA1, serpin peptidase inhibitor, clade A, an elastase inhibitor) in HDL, isolated either by ultra‐centrifugation or by selected‐affinity immunosorption using an anti‐apoA‐I column. Furthermore, we report that HDL possesses potent antielastase activity. We further showed that only HDL but not LDL is able to bind AAT. HDL‐associated AAT was able to inhibit extracellular matrix degradation, cell detachment, and apoptosis induced by elastase in human vascular smooth muscle cells (VSMCs) and in mammary artery cultured ex vivo. Degradation of fibronectin by elastase used as a marker of pericellular proteolysis was prevented by addition of HDL. Elastase present in aortic abdominal aneurysm (AAA) thrombus samples was also able to induce apoptosis of VSMCs in culture. This phenomenon was prevented by addition of HDL but not of LDL. Finally, we report that the proportion of AAT in HDL isolated from patients with an AAAis decreased relative to that from matched control subjects, suggesting a reduced capacity of HDL to inhibit elastase in these patients. In conclusion, our data provide evidence of a new potential antiatherogenic property of HDL attributable to AAT and its antielastase activity.—Ortiz‐Munoz, G., Houard, X., Martin‐Ventura, J.‐L., Ishida, B. Y., Loyau, S., Rossignol, P., Moreno, J.‐A., Kane, J. P., Chalkley, R. J., Burlingame, A. L., Michel, J.‐B., Meilhac, O. High‐density lipoprotein antielastase activity prevents smooth muscle cell anoikis, a potential new antiatherogenic property. FASEB J. 23, 3129–3139 (2009). www.fasebj.org