Apolipoprotein H, a new mediator in the inflammatory changes ensuing in jeopardised human myocardium

H W M Niessen¹, W K Lagrand², H J A M Rensink³, Ch J L M Meijer¹, L Aarden³, C E Hack³

¹ Department of Pathology, Free University Hospital, PO Box 7057, De Boelelaaan 1117, 1081 HV Amsterdam, The Netherlands
² Department of Cardiology, Free University Hospital
³ CLB, Sanguin Blood Supply Foundation Service, PO Box 9190, 1006 AD Amsterdam, The Netherlands

Correspondence to:
Dr Niessen jwm.niessen{at}azvu.nl

Aim—To investigate the presence of membrane "flip flop" in ischaemic human myocardium, we assessed depositions of apolipoprotein H (apoH; ß2-glycoprotein 1) in ischaemic myocardium. Serum protein apoH can bind to negatively charged phospholipids and can also inhibit blood coagulation in vitro. We hypothesised that, because of its affinity for phosphatidyl serine, apoH might bind to "flip flopped" cells and would therefore be useful as a marker for membrane flip flop in vivo.

Methods—Myocardial tissue specimens were obtained from patients who had died within 14 days of acute myocardial infarction.

Results—Immunohistochemical analysis of these specimens revealed that apoH was selectively deposited in infarcted areas of human myocardium of at least one day's duration. Depositions of apoH were not found in non-ischaemic myocardial tissue samples obtained from patients who died from other (extracardial) causes. In vitro experiments with the human leukaemia T cell line Jurkat, subjected to apoptosis by etoposide, showed that apoH was bound to the membrane of apoptotic cells. However, these experiments also indicated that flip flop itself is not sufficient for apoH binding. In addition, Jurkat cells that bound apoH were positive for activated complement complexes, as was also found in the human heart.

Conclusions—These results suggest that apoH is involved in the inflammatory processes that occur in ischaemic myocardium.

Key Words: myocardium • apolipoprotein H • inflammation • complement

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Simo, R., Higuera, M., Garcia-Ramirez, M., Canals, F., Garcia-Arumi, J., Hernandez, C. (2008). Elevation of Apolipoprotein A-I and Apolipoprotein H Levels in the Vitreous Fluid and Overexpression in the Retina of Diabetic Patients. Arch Ophthalmol 126: 1076-1081 [Abstract] [Full Text]  
• Krijnen, P A J, Ciurana, C, Cramer, T, Hazes, T, Meijer, C J L M, Visser, C A, Niessen, H W M, Hack, C E (2005). IgM colocalises with complement and C reactive protein in infarcted human myocardium. J. Clin. Pathol. 58: 382-388 [Abstract] [Full Text]  
• Nijmeijer, R., Lagrand, W. K., Lubbers, Y. T. P., Visser, C. A., Meijer, C. J. L. M., Niessen, H. W. M., Hack, C. E. (2003). C-Reactive Protein Activates Complement in Infarcted Human Myocardium. Am. J. Pathol. 163: 269-275 [Abstract] [Full Text]