We examined serum markers for atherothrombotic risk in several studies: 1) Electrophoresis coupled with enzymatic detection of cholesterol in agarose gel has the advantage of allowing simultaneous measurement of cholesterol in all major lipoprotein fractions at a comparatively low cost. Although these methods have been evaluated analytically, information regarding possible interferences is limited. We observed a case in which gross errors occurred in the measurement of LDL-C and VLDL-C with such a commercial method. Based on our detailed analysis of the patient's serum lipoproteins, the erroneous LDL-C and VLDL-C results were due to a fast-migrating, abnormally composed LDL that has changed over a sixth-month period. However, occurrence of this anomalous LDL could not be correlated with medications, other laboratory findings and/or clinical course. While the frequency of this anomalous LDL among clinical specimens and with other cholesterol electrophoretic methods is presently not known, this case suggests that unexpected and/or unexplainable combination of very low LDL-C and high VLDL-C results with these methods should be verified by alternative techniques. 2) In a collaborative study, we studied patients with sickle cell disease for endothelial nitric oxide bioavailability. Similar to atherosclerotic vascular disease, sickle cell disease is characterized by chronic inflammation and ischemia-reperfusion injury. Plasma CRP levels were indeed elevated in these patients and were correlated with other markers of inflammation such as ferritin and white blood cell count. Further, we found divergent endothelial nitric oxide bioavailability by gender (females more than males). The findings may explain the sex differences reported for morbidity and mortality in these patients. 3) In a collaborative study, we observed that, probably through multiple effects on a cell response to stress, high levels of human heat shock protein 70 are associated with low coronary artery disease risk. 4) In another collaborative study, we showed that Cla-1, the human orthologue of rodent scavenger receptor BI, not only is a major receptor for HDL that mediates reverse cholesterol transport, but also is able to bind and internalize both monomerized, lipoprotein-free and and HDL-associated bacterial endotoxins (lipopolysaccharides). This suggests that Cla-1 may play an important role in septic shock by affecting the cellular uptake and clearance of lipopolysaccharides.
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