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Commentary

National Institutes of Health, Bethesda, MD.

Address correspondence to the author at: Bldg 10 7N115, 10 Center Drive, National Institutes of Health, Bethesda, MD, 20892-1666. Fax: 301-402-0190; e-mail bobs{at}nhlbi.nih.gov.

Clinical laboratories typically focus on apolipoprotein (apo)E typing of polymorphisms (E2, E3, E4) and less on apoE concentrations, because increased apoE is found in hypertriglyceridemia but correlates less with coronary heart disease. The role of apoE and the importance of splenic macrophages in lipoprotein metabolism are highlighted by this case.

Type III hyperlipoproteinemia (HLP) is inherited either in a recessive or dominant mode. Recessively inherited type III HLP requires homozygosity of apoE2, but E2/2 alleles alone are not enough for development of the lipid and clinical phenotype, because <10% of apoE2/2 homozygotes produce the phenotype. A "second hit" consisting of genetic, hormonal, and environmental factors including obesity, estrogen status, or diabetes are required to develop the phenotype. In contrast, apoE3 149Leu is a rare dominantly inherited form of type III HLP that is attributable to a single defective apoE allele. This phenotype lacks the "classical" tuberous and palmar xanthoma seen in recessive type III HLP, and the lipid profile in apoE3 149Leu depends more on an intact spleen than a second hit.

The spleen plays an important and protective role in clearing the plasma of triglyceride-remnant lipoproteins. Development of hepatosteatosis and splenomegaly appears to occur as a result of hypercatabolism of mutant apoE-containing triglyceride-remnant lipoproteins by splenic macrophages. Enhanced macrophage uptake contributes to the relatively normal plasma lipid concentrations with an intact spleen.

Splenectomy unmasks the remnant lipoprotein defect and leads to the development of hypertriglyceridemia. Then, diet and secondary factors modulate the overproduction of lipoproteins (β-VLDL) concomitantly with the defective removal.

The spleen plays an important role in the abnormal clearance that occurs in other lipid disorders such as Tangier disease. The clinical picture can worsen after splenectomy. Atherosclerosis is accelerated after splenectomy owing to the decreased clearance of remnant lipoproteins, but may take 5–10 years to be clinically apparent. Splenic macrophages may be protective against the development of coronary heart disease.

Acknowledgments

Grant/funding Support: None declared.

Financial Disclosures: None declared.

References

1. Schaefer EJ, Triche TJ, Zech LA, Stein LA, Kemeny MM, Brennan MF, Brewer HB, Jr. Massive omental reticuloendothelial cell lipid uptake in Tangier disease after splenectomy. Am J Med 1983;75:521-526.[CrossRef][Medline] [Order article via Infotrieve]

This Article Extract Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shamburek, R. Search for Related Content PubMed Articles by Shamburek, R. Related Collections Clinical Case Studies