Evaluation of the Sialic Acid Content of LDL as a Marker of Coronary Calcification and Extracoronary Atherosclerosis in Asymptomatic Hypercholesterolemic Subjects

Abstract

Recent studies have shown that the sialic acid content of LDL isolated from patients with angiographically demonstrated advanced coronary atherosclerosis is lower than that of LDL isolated from healthy subjects. These observations raise the question as to whether LDL sialic acid content could be used as an early marker of atherosclerosis. We screened for carotid, aortic, and femoral plaques by ultrasonography and for coronary calcifications by ultrafast computed tomography in 160 hypercholesterolemic subjects free of cardiovascular disease to investigate the relation between LDL sialic acid content and the prevalence of these early atherosclerotic lesions. LDL sialic acid values varied from 19.6 to 46.6 nmol/mg LDL protein (33.9 +/- 4.4, mean +/- SD) in the whole population, but the distribution was very similar: (1) in subjects with no plaque (34.1 +/- 4.9) relative to those with one or several plaques at one (34.2 +/- 4.4), two (33.0 +/- 3.6), or three (34.8 +/- 3.4) different arterial sites; (2) in subjects with (33.9 +/- 3.7) and without (34.1 +/- 4.8) coronary calcification; and (3) in subjects with both extracoronary and coronary lesions (33.8 +/- 3.9) relative to those with no arterial lesions (34.2 +/- 4.5). LDL sialic acid content was not related to sex, age, body mass index, smoking, blood pressure, or serum total cholesterol and lipoprotein(a) levels but correlated negatively with serum triglyceride levels (P < .001). These results suggest that LDL sialic acid content is not a discriminant marker of early atherosclerosis in asymptomatic hypercholesterolemic subjects.

Sialic Acid Content of LDL in Coronary Artery Disease: No Evidence of Desialylation in Subjects With Coronary Stenosis and Increased Levels in Subjects With Extensive Atherosclerosis and Acute Myocardial Infarction

“…23 To test whether LDL sialic acid content could be used early for effective prevention of atherosclerosis, we recently examined hypercholesterolemic subjects with and without subclinical atherosclerosis. 24 Surprisingly, we found no relation between LDL sialic acid content and the prevalence of peripheral plaques and/or coronary calcifications detected respectively by high-resolution ultrasonography and ultrafast CT. As our population consisted of asymptomatic subjects, we postulated that desialylation of LDL might occur much later in the atherosclerotic process. Only two other groups studied LDL sialic acid content in patients with and without documented CAD.…”

“…24,28 LDL (dϭ1.019 to 1.063 g/mL) was isolated by sequential ultracentrifugation in a Beckman L90 ultracentrifuge (Beckman Instruments Inc) according to a procedure previously described in detail. 24 Collected LDL was dialyzed for 24 hours at ϩ4°C against four changes of 100 vol 10 mmol/L Tris-HCl buffer, pH 7.4, containing 1 mmol/L EDTA, and was stored at ϩ4°C in the dark.…”

“…24,28 LDL (dϭ1.019 to 1.063 g/mL) was isolated by sequential ultracentrifugation in a Beckman L90 ultracentrifuge (Beckman Instruments Inc) according to a procedure previously described in detail. 24 Collected LDL was dialyzed for 24 hours at ϩ4°C against four changes of 100 vol 10 mmol/L Tris-HCl buffer, pH 7.4, containing 1 mmol/L EDTA, and was stored at ϩ4°C in the dark. For in vitro studies, LDL was isolated by preparative ultracentrifugation from normolipidemic plasma pools according to a procedure previously described in detail 6,29 and then dialyzed as indicated above.…”

“…24 Briefly, bound sialic acid was released from sialoglycoconjugates by mild hydrolysis (15 minutes at 80°C in 0.05 mol/L H 2 SO 4 ). Warren's periodate-TBA assay 30 was used.…”

Sialic acid in cardiovascular diseases

“…Contradictory reports on the role of LDL sialic acid content in atherogenesis are also available. Chappey et al (53) showed that LDL sialic acid content is not a discriminant marker of early atherosclerosis in asymptomatic hypercholesterolemic subjects. Later on they (54) showed that LDL sialic acid content was increased in patients with both coronary stenosis and peripheral arterial atherosclerosis lesions compared with either no lesions or only one or the other type of lesions.…”