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Release of Activin and Follistatin during Cardiovascular Procedures Is Largely due to Heparin Administration¹

Monash Institute of Reproduction and Development (D.J.P., K.L.J., D.M.d.K.) and the Center for Heart and Chest Research (D.J.M., J.J.S.), Monash University, Clayton, Victoria 3168, Australia; Oxford Brookes University (N.P.G.), Oxford 0X3 0PB, United Kingdom; and Department of Surgery, St. Vincent’s Hospital (H.P.), Sydney, New South Wales 2010, Australia

Address all correspondence and requests for reprints to: Dr. D. J. Phillips, Monash Institute of Reproduction and Development, Monash Medical Center, 246 Clayton Road, Clayton, Victoria 3168, Australia. E-mail: david.phillips{at}med.monash.edu.au

Recent evidence has suggested that activin A complexed to its binding protein, follistatin, may be present on the surface of cells through their interaction with heparan sulfate proteoglycans. As heparin is used routinely in many cardiovascular procedures for its anticoagulation properties, it may also cause the release of heparin-binding growth factors, including activin and follistatin, from the vascular endothelium. We examined the effect of two cardiovascular procedures and the use of heparin directly on the circulating concentrations of activin A and follistatin. A rapid and robust release of activin A and follistatin occurred in the circulation of patients undergoing abdominal aortic aneurysm repair or carotid endarterectomy at the time of vessel clamping and administration of heparin (5000 IU). This release pattern was dissimilar to that of the inflammatory marker, interleukin-1ß. However, administering heparin (2500 IU) to coronary angiography patients produced a similar activin and follistatin response, whereas placebo-treated angiography patients had no response. These findings illustrate that the routine use of heparin in surgical procedures elicits a rapid and robust release of activin and follistatin. This has direct clinical relevance by potentially activating heparin-binding growth factors that are important in injury, hyperplasia, and restenosis of vessels.

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