Tissue distribution of [3H]cholesteryl linoleyl ether-labeled human Lp(a) in different rat organs.
The sites of tissue uptake of human lipoprotein(a) (Lp(a] were studied in rats using [3H]cholesteryl linoleyl ether [( 3H]CLE) as a marker. Since rat plasma has no cholesteryl ester transfer activity, the amount of label in various tissues should reflect the quantitative uptake of Lp(a). Isolated Lp(a) was labeled with [3H]CLE by incubation overnight of Lp(a), a source of cholesteryl ester transfer activity (1.23 g/ml infranate of human plasma), and [3H]CLE-labeled Intralipid. Following labeling, the homogeneity and integrity of Lp(a) was shown by agarose electrophoresis and immunoblotting. Intact Lp(a) was injected via the tail vein of rats (120-170 g, n = 4 at each time point), and tissues were collected at various times thereafter (4-48 h). The disappearance curve of [3H]CLE-labeled Lp(a) from rat plasma was bimodal and had an initial rapid t1/2 of 1.8 h followed by a slower component, t1/2 = 13.3 h. Tissue uptake at all sampling times was greatest in liver (28.5% at 48 h of total dpm injected), followed by the intestine (9-12%), with less than 3% uptake by spleen. The small intestine was divided into four segments, and while the 3H radioactivity was similar in the proximal segments, a time-related increase in [3H]CLE was seen in its most distal portion. These studies indicate that the tissue sites of degradation in the rat of human Lp(a) are similar to human low-density lipoproteins (LDL); the increase in label in the distal portion of the small intestine with time may represent [3H]CLE excreted through the bile and absorbed by the mucosal cells.
Ye
S Q
SQ
Oklahoma Medical Research Foundation, Oklahoma City 73104.
Keeling
J
J
Stein
O
O
Stein
Y
Y
McConathy
W J
WJ
D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives*; D004587:Electrophoresis, Agar Gel; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007122:Immunoelectrophoresis; D007163:Immunosorbent Techniques; D007421:Intestine, Small / Q000378:metabolism; D007553:Isotope Labeling; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution; D014316:Tritium
D005217:Fat Emulsions, Intravenous; D017270:Lipoprotein(a); D008074:Lipoproteins; D014316:Tritium; C027575:cholesteryl linoleyl ether; D002784:Cholesterol