Regulation of PGI 2 activity by serum proteins: serum albumin but not high density lipoprotein is the PGI 2 binding and stabilizing protein in human blood

Abstract

Although previous studies have shown that serum albumin binds PGI 2 and protects it from rapid degradation, it remains debatable whether it is physiologically important due to its low binding affinity for PGI 2. We were intrigued by the observations of Yui et al. (J. Clin. Invest. 82 (1988) 803–807) which suggested that apo A-I of the high density lipoprotein (HDL) is the “serum PGI 2 stabilizing factor”. To clarify this, we carried out experiments to determine the binding kinetics and parameters of HDL and albumin purified from normal pooled human serum. Despite the use of multiple binding assays, we could not detect any binding activity in HDL 2, HDL 3 or nascent HDL preparations, nor could we demonstrate any PGI 2 protecting activity by these molecules. By contrast, purified albumin exhibited essentially identical binding parameters as the native serum from which the albumin was purified. The binding activity of various albumin preparations was not due to the contamination of apo A-I. Computer simulation analysis also failed to provide evidence to support the notion that HDL bound and prolonged PGI 2 activity. To determine whether physiological concentrations of albumin influence PGI 2 binding to platelet receptors, we measured PGI 2 binding to platelet membrane in the absence and presence of albumin. Albumin at 40 mg/ml increased the K D of PGI 2 binding to the receptors by 2–3-fold. These findings indicate that albumin plays a major role in protecting PGI 2 activity and regulating its availability for platelet PGI 2 receptors.