CELLULAR PATHOLOGY OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

  • 1 January 1979
    • journal article
    • research article
    • Vol. 97  (2) , 327-+
Abstract
Tissues were studied from 4 subjects with homozygous familial hypercholesterolemia (FH). The specimens consisted of tissues obtained from a 20 wk old fetus at autopsy, samples from a 9 yr old girl during open heart surgery, and biopsies of cutaneous xanthomas from a 13 yr old girl and a 21 yr old man. The FH fetus, but not the 3 control fetuses, exhibited multifocal lipid deposition particularly involving the stromal cells of the thymus, spleen and skin and both the stromal and parenchymal cells of the kidney. Only 1 minute focus of intimal lipid accumulation was found in the aorta and coronary arteries of the FH fetus. A segment of the ascending aorta from the 9 yr old girl showed foam-cell transformation of many medial smooth muscle cells, abnormal vascularization of the inner media and intima and intimal involvement by a typical artherosclerotic plaque with lipid deposits in thin, elongated cells that showed some myocytic features and in foam cells that lacked such features. The mitral and aortic valves of this patient also contained numerous foam cells and showed mild to moderate fibrous thickening. A segment of the saphenous vein contained no lipid deposits. The 3 xanthomas from 2 FH homozygotes exhibited marked lipid accumulation in histiocytic foam cells but no lipid deposits in the endothelium of blood vessels in the lesions. The findings in this study, in conjunction with those reported in studies of other FH homozygotes, indicate that homozygous FH is characterized by accelerated atherosclerosis and prominent lipid accumulation in macrophages and other stromal cells of the aortic and mitral valves, skin, tendon and, variably, in other extravascular sites. Since most of the intracellular lipid was in the form of non-membrane-bound neutral lipid droplets, it appears that the cytoplasm is the major site of lipid storage in this disease.