Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.

Abstract

Lp[a] is a lipoprotein whose plasma concentration is highly correlated with cardiovascular disease. Its protein moiety, apoLp[a], consists of two large polypeptides, apo[a] and apo B. The possible contribution of Lp[a] to atherosclerosis in saphenous vein aortocoronary bypass grafts was studied in a population of patients undergoing coronary re-bypass surgery. The vein graft tissue levels of apoLp[a] were compared with graft duration, gross and light microscopic pathology, as well as plasma levels of apoLp[a]. The localization pattern of apo[a] and apo B in vein graft tissue was determined. In addition, the plasma levels of cholesterol, triglycerides, apoproteins (apo) A-I, A-II, and E were measured. In a representative subpopulation of 17 patients with a mean age of 63 years from whom grafts with a mean duration of 112 months were resected, the mean total plasma cholesterol level was 221 mg/dl, the mean high density lipoprotein cholesterol level was 31 mg/dl, and the mean plasma triglyceride level was 228 mg/dl. In normal saphenous veins, the level of apoLp[a] was below measurable limits (less than 2 ng/mg), and the level of apo B was very low (3.3 ng/mg). In resected grafts, the mean tissue level of apoLp[a] was 32 ng/mg, and that of apo B was 70 ng/mg, demonstrating the net accumulation of these apoproteins in veins from the time of their grafting into the arterial bed. The apoLp[a]/apo B ratio was determined in 77 tissue segments from 59 grafts (28 patients) and was found to be 0.313. This tissue ratio was significantly higher (p = 0.02) than the plasma apoLp[a]/apo B ratio from these patients, which was 0.132. Immunostaining showed co-localization of apo[a] and apo B in the neointima of grafts. The most abundant pathologic features observed in resected grafts were proliferated intima (43/52), thrombus (28/52), and atherosclerotic core regions (21/52). The level of tissue apo B correlated well with the abundance of core regions (r = 0.501), whereas the level of tissue apoLp[a] did not correlate as well with this feature (r = 0.233). Although apo[a] and apo B are almost absent from normal saphenous vein, these apoproteins (and presumably the lipoproteins Lp[a] and low density lipoprotein) accumulate in bypass vein grafts. The data support the view that these lipoproteins play a significant role in vein graft atherosclerosis.