β2‐glycoprotein I protects J774A.1 macrophages and human coronary artery smooth muscle cells against apoptosis

Abstract

beta(2)-Glycoprotein I (beta(2)-GPI) is a plasma glycoprotein with multifactorial relevance to clinical consequences. It was previously indicated that beta(2)-GPI can selectively bind to apoptotic cells. This study was designed to determine the role of beta(2)-GPI in apoptosis. Using an immunohistochemical study, we observed that beta(2)-GPI was co-localized with the apoptotic macrophages and smooth muscle cells (SMCs) of human coronary arteries. The contribution of beta(2)-GPI to apoptotic death was then investigated in vascular cells. Two nitric oxide (NO) donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl penicillamine (SNAP) were used in this study to trigger apoptosis in J774A.1 macrophages and human coronary artery smooth muscle cells (HCASMC). Cell viability was significantly improved in beta(2)-GPI-treated cells. It was also possible to detect a remarkable inhibitory effect by beta(2)-GPI on the NO-induced apoptosis by preventing nuclear shrinkage. Furthermore, the NO-induced apoptosis was associated with increase in caspase-3 activity and in the protein levels of caspase-3, c-Fos, and c-Jun. However, all these apoptosis-related events were inhibited in vascular cells treated with 200 microg/ml beta(2)-GPI. This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells.