Long-Term Kinetics of Serum and Xanthoma Cholesterol Radioactivity in Patients with Hypercholesterolemia

Samuel, Paul; Perl, William; Holtzman, Charles M.; Rochman, Norman D.; Lieberman, Sidney

doi:10.1172/jci106811

Cited by 44 publications

(15 citation statements)

References 19 publications

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“…We believe that these findings suggest a net efflux of more richly labeled cholesterol from the shrinking adipose tissue mass; Samuel, Perl, Holtzman, Rochman, and Lieberman have also noted higher specific activities in this tissue than in plasma, after administering radioactive cholesterol intravenously, in a nonobese hypercholesterolemic patient (28).…”

Section: Discussionmentioning

confidence: 67%

Cholesterol Metabolism in Human Obesity

Nestel¹,

Schreibman²,

Ahrens³

1973

J. Clin. Invest.

147

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Section: Discussionmentioning

confidence: 67%

Cholesterol Metabolism in Human Obesity

Nestel¹,

Schreibman²,

Ahrens³

1973

J. Clin. Invest.

147

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“…Clearly, with severe atherosclerosis and a very large pool of unlabeled cholesterol which would dilute greatly the entering labeled cholesterol, a longer time period would be required for equilibration. In other studies, when the lesions were less severe and the time periods longer, from 137 to 371 days, this crossover phenomenon of atheroma and plasma cholesterol sp act was demonstrated (3,5,7).…”

mentioning

confidence: 68%

“…Previous radioisotopic exchange studies in patients with limited life expectancy have indicated that the tracer cholesterol fed orally or administered intravenously could be detected in the aorta and other arteries at autopsy (2)(3)(4)(5)(6)(7). Since the labeled cholesterol was incorporated into the plasma lipoproteins after its administration (2,8), these results demonstrated a measure of equilibration of cholesterol between plasma and arterial tissues.…”

Section: Introductionmentioning

confidence: 81%

The Turnover of Cholesterol in Human Atherosclerotic Arteries

Jagannathan¹,

Connor²,

Baker³

et al. 1974

J. Clin. Invest.

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A B S T R A C T The equilibration of cholesterol between plasma and atherosclerotic arteries was studied in 13 latients with obstructive atherosclerosis 2-96 days after the intravenous and/or oral administration of isotopic cholesterol. Arterial specimens were obtained in 12 patients during surgery for arterial reconstruction and in a 13th patient at autopsy. Equilibration was calculated as the specific radioactivity of cholesterol in the arterial tissue relative to that in the plasma (percent).In specimens obtained 2-4 days after pulse labeling, the specific activity of cholesterol in atheroma ranged from 0.3 to 4.5% of that in the plasma. By 17-27 days, the relative specific activity ranged from 6 to 20% in different arteries. In contrast, cholesterol of skeletal muscle had a relative specific activity of 96% by 22 days. By 61-96 days, atheroma cholesterol in the abdominal aorta, common iliac, and femoral arteries had equilibrated to 55, 30, and 26%, respectively. In the patient who died at 96 days, the cholesterol in the coronary arteries had a mean equilibration of 66%, similar to the values for the abdominal (66%) and thoracic (57%) aortas. The route of administration of the isotope did not influence the equilibration.Within the atheromatous plaque, the superficial layers equilibrated better than the deeper layers (75% vs. 22%). The free cholesterol in the atheroma equilibrated to a significantly higher extent than did esterified cholesterol (59% vs. 38%). There was a fourfold higher specific activity of cholesterol in the media than in the corresponding intima (916 vs. 230 dpm/mg).The estimated minimal influx rates of plasma cholesterol into the atheromatous intima ranged from 0.065 to 0.274 mg of cholesterol/g dry tissue per day for different arteries. The approximated turnover times of atheroma cholesterol ranged from 442 days for the abdominal aorta and the coronary arteries to 580 days for the common iliac and 821 and 934 days, respectively, for the femoral and the carotid arteries. These data indicate a definite, though slow, exchange of cholesterol between the plasma and severely atherosclerotic human arteries. Within the atheroma, there are multiple pools of cholesterol, each turning over differently and more slowly than the cholesterol of most other tissues, such as the skeletal muscle. The estimates of influx rate and turnover time of atheroma cholesterol suggest the possibility that this cholesterol is mobilizable, an indication of potential regression of atheromatous lesions in man. INTRODUCTIONPrevious radioisotopic exchange studies in patients with limited life expectancy have indicated that the tracer cholesterol fed orally or administered intravenously could be detected in the aorta and other arteries at autopsy (2-7). Since the labeled cholesterol was incorporated into the plasma lipoproteins after its administration (2,8) (iodine, no. 80-85) and a cholesterol content of 100 mg for periods of a few months to 1 year before their enrollment in the study.Patient 13 had been given a cholest...

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“…In 12 of the 17 patients a third exponential appeared after 25 wk, and probably reflected a third kinetic pool of more slowly exchangeable cholesterol. Samuel, Perl, Holtzman, Rochman, and Lieberman in another study also noted that if xanthomata were present, the specific activity of xanthoma cholesterol differed widely from plasma cholesterol specific activity and indicated that this cholesterol might constitute a fourth more slowly exchangeable kinetic pool (32) and might be a problem in patients with xanthomatosis. When the various kinetic parameters were derived by input-output analysis and compared with similar values obtained from analysis of 10-12-wk segments of the same curves, important quantitative differences between the short-term and long-term kinetic values were noted.…”

Section: Plasma Cholesterol and Cholestanol Concentrationsmentioning

confidence: 96%

The Metabolism of Cholestanol, Cholesterol, and Bile Acids in Cerebrotendinous Xanthomatosis

Salen¹,

Grundy²

1973

J. Clin. Invest.

163

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A B S T R A C T The metabolism of cholesterol and its 5-dihydro derivative, cholestanol, was investigated by means of sterol balance and isotope kinetic techniques in 3 subjects with cerebrotendinous xanthomatosis (CTX) and 11 other individuals. All subjects were hospitalized on a metabolic ward and were fed diets practically free of cholesterol and cholestanol. After the intravenous administration of [1,2-3H]cholestanol, the radioactive sterol was transported and esterified in plasma lipoproteins in an identical manner to cholesterol. In these short-term experiments, the specific activity-time curves of plasma cholestanol conformed to two-pool models in both the CTX and control groups. However, cholestanol plasma concentrations, total body miscible pools, and daily synthesis rates were two to five times greater in the CTX than control individuals. The short-term specific activity decay curves of plasma [4Y'tC]cholesterol also conformed to two-pool models in both groups. However, in the CTX subjects the decay was more rapid, and daily cholesterol synthesis was nearly double that of the control subjects. Plasma concentrations and the sizes of the rapidly turning over pool of exchangeable cholesterol were apparently small in the CTX subjects, and these measurements did not correlate with the large cholesterol deposits found in tendon and tuberous xanthomas.Despite active cholesterol synthesis, bile acid formation was subnormal in the CTX subjects. However, bile acid sequestration was accompanied by a rise in plasma cholestanol levels and greatly augmented fecal cholesDr.

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Long-Term Kinetics of Serum and Xanthoma Cholesterol Radioactivity in Patients with Hypercholesterolemia

Cited by 44 publications

References 19 publications

Cholesterol Metabolism in Human Obesity

Cholesterol Metabolism in Human Obesity

The Turnover of Cholesterol in Human Atherosclerotic Arteries

The Metabolism of Cholestanol, Cholesterol, and Bile Acids in Cerebrotendinous Xanthomatosis

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