Background-Hypoalphalipoproteinemia is the most common lipoprotein abnormality in patients with coronary artery disease, yet its causes are unknown. Methods and Results-We show that the homozygous staggerer (sg/sg) mutant mouse, which carries a deletion within the nuclear receptor ROR␣ gene, develops severe atherosclerosis when maintained on an atherogenic diet. In addition, sg/sg mice display a profound hypoalphalipoproteinemia, which is associated with decreased plasma levels of the major HDL proteins, apolipoprotein (apo) A-I and apoA-II. This decrease in HDL levels in sg/sg mice is due to lowered apoA-I gene expression in the intestine but not in the liver. ApoA-II gene expression is unaffected. Conclusions-These results suggest that the ROR␣ gene contributes to the plasma HDL level and susceptibility to atherosclerosis. (Circulation. 1998;98:2738-2743.)

Plasmasorption on a heparin-based sorbent was performed in vitro. It demonstrated affinity of the C3a and C5a anaphylatoxins for the sorbent: C3a was removed almost completely (97%), and the C5a concentration decreased on average by 55%. The plasma level of C3a and C5a complement components was also monitored during the procedure of clinical extracorporeal low density lipoprotein (LDL) apheresis on the sorbent in patients with familial hypercholesterolemia. A two- to threefold increase in C3a (up to 1,500 ng/ml) was observed after plasma separation by the IBM 2997 cell sorter. Subsequent processing of the plasma through the column led to the low level of C3a detected (less than 50 ng/ml), demonstrating significant uptake of C3a by the sorbent column. The removed C3a was found in the eluate obtained after regeneration of the sorbent with 2 M NaCl solution. No significant increase in C5a was found during the procedure. Nevertheless, some C5a was detected in the eluate from the sorbent. The content of C3a and C5a in patients blood after the treatment was approximately the same as it was initially, 200-500 ng/ml for C3a and less than 10 ng/ml for C5a. The removal of C3a and C5a anaphylatoxins by heparin-based sorbent should be regarded as an advantage of this type of plasmasorbent.

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Heparin-sorbent was developed in the USSR Cardiology Research Center for LDL-apheresis in patients with familial hypercholesterolemia. Clinical trials of the sorbent were started in 1985. Heparin-sorbent has a high capacity for LDL. One column (400ml) can remove 3 - 6g of LDL cholesterol, depending on the initial LDL content in the plasma. The sorbent demonstrates a high stability, it can withstand more then 75 sorbtion-desorbtion cycles with only a slight loss of the initial capacity. It means that one column can work for 1,5-2,0 years when used weekly. Heparin-sorbent is the sorbent of limited selectivity, apo-B content in eluate is 40-60% of the total protein content, but it is important that it does not bind HDL.

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