Serum apolipoprotein J in health, coronary heart disease and Type 2 diabetes mellitus

Apolipoprotein (apo) J, clusterin, is ubiquitously expressed in many tissues, and is a component of high-density lipoproteins (HDLs). There is experimental evidence that it may be anti-atherogenic through its effects on cholesterol transport, smooth muscle cell proliferation and lipid peroxidation. HDLs containing apo J and apo A-I carry paraoxonase (PON 1), which protects low-density lipoproteins from oxidative modification; however, the extent to which apo J affects coronary heart disease (CHD) is not known. We have developed a sandwich ELISA that enables apo J to be assayed in the range of 13-200 mu g/mL. Serum apo J was 52.8 +/- 0.8 mu g/mL (mean +/- SEM; range, 36.0-84.3 mu g/mL; n = 92) in healthy Japanese men, and 49.3 +/- 0.5 mu g/mL (34.5-72.8; n = 241) in healthy Japanese women. Multiple regression of these data and results from 67 men with CHD showed that apo J concentration was unrelated to age, sex or body mass index, but was positively related to serum PON1 (p < 0.001) and apo B (p < 0.02) concentrations. In women, it was also positively related to blood glucose (p < 0.02). After adjusting for its associations with covariates, serum apo J averaged 5.4 mu g/mL, lower in CHD men than in controls (p < 0.003). Type 2 diabetics had higher apo J concentrations (men, 83.1 +/- 3.4 mu g/mL, n=64; women, 64.0 +/- 2.3 mu g/mL, n=46) than healthy men and women (p< 0.001). In these Type 2 diabetics, apo J concentration was unrelated to PON1 concentration, but was positively related to blood glucose (p < 0.01). After adjustment for its relation to blood glucose, the mean apo J concentration was similar in diabetics and healthy subjects. These findings suggest that apo J may be anti-atherogenic in humans, and that its concentration is raised by Type 2 diabetes.