Abnormal Lipid Deposition Research Articles

Cellular pathology of progressive atherosclerosis in the WHHL rabbit. An animal model of familial hypercholesterolemia.

This report describes the features of developing atherosclerosis in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of human familial hypercholesterolemia. Observations were made in 18 homozygous WHHL rabbits, aged 4 days to 15 months, fed standard rabbit chow; seven control New Zealand white rabbits fed a similar diet, and four New Zealand white rabbits fed rabbit chow containing 2% cholesterol and 10% corn oil for 2 weeks. The WHHL rabbits showed evidence of progressive disease of the aorta with accumulation of strongly birefringent lipid in intimal lesions, including fatty streaks, raised foam cell lesions, and plaques (atheromas), as well as in the media. As seen by electron microscopy, the cellular population of the intimal lesions consisted predominantly of smooth muscle cells with lipid deposits and lipid-laden foam cells. Lipid deposits occurred as cytoplasmic neutral lipid droplets and as multilamellar bodies. In addition to advanced atherosclerosis of the aorta, a 15-month-old WHHL rabbit also had focal coronary atherosclerosis and subcutaneous xanthomas. The New Zealand white rabbits fed a high cholesterol and fat diet for 2 weeks showed early intimal lipid accumulation in the aorta and prominent lipid accumulation in hepatocytes and macrophages of the liver and spleen. New Zealand white rabbits fed the standard rabbit chow had no abnormal lipid deposits. In contrast to the cholesterol-fed rabbits, WHHL rabbits had only mild lipid accumulation in other tissues. Thus, many similarities exist between atherosclerotic disease in the WHHL rabbit and in man. This study shows that the WHHL rabbit is a good model of familial hypercholesterolemia.

Peripheral nerve involvement in Fabry's disease.

ANGIOKERATOMA corporis diffusum or Fabry's disease is a genetically determined disorder of lipid metabolism which displays a sex-linked recessive transmission. In hemizygous male subjects, it produces the characteristic skin lesions, dilated conjunctival blood vessels, and corneal opacities, together with renal failure, and cerebral and cardiac complications. In the heterozygous female subjects, abnormalities are usually limited to the eyes, although the abnormal lipid deposits have been dected in other organs. The abnormality responsible for the disorder has been shown by Brady et al 1 to be a deficiency of ceramide trihexosidase, which results in the accumulation of ceramide trihexoside in various tissues. 2,3 The clinical manifestations of the disease 4,5 are thought to be due either to direct involvement of various tissues by lipid deposits or to arise secondarily to vascular disease from involvement of small arteries and arterioles. Frequently, an organ such as the heart, kidney, or brain may be

Lipid alterations in beagles produced by atherogenic stress and vitamin A

Summary The application of atherogenic stress (ATCH, thiouracil and high fat diet) to purebred beagles resulted in the following lipid alterations: (1) increased serum cholesteryl esters and total lipid and decreased triglycerides; (2) increased triglycerides and decreased phospholipids of all organs; (3) increased free cholesterol of arterial segments and (4) increased percentages of saturated fatty acids associated with esterified lipids. Vitamin A supplementation produced the following modification of lipid changes produced by atherogenic stress: (1) increased all serum lipid fractions above atherogenic levels with the exception of free cholesterol; (2) increased phospholipid content of all organs; (3) increased all arterial lipid levels except that of free cholesterol, which was lowered and (4) reduced percentages of saturated fatty acids in esterified lipid. From these observations it appears that vitamin A may have a usefulness in alleviating abnormal lipid deposition produced by atherogenic stress by retarding the deposition of free cholesterol in arterial segments.

Cytological studies of organotypic cultures of rat dorsal root ganglia following X-irradiation in vitro. I. Changes in neurons and satellite cells.

Long-term organotypic cultures of rat dorsal root ganglia were exposed to a single 40 kR dose of 184 kvp X-rays and studied in the living and fixed states by light or electron microscopy at 1-14 day intervals thereafter. Within the first 4 days following irradiation, over 30% of the neurons display chromatolytic reactions (eccentric nuclei, peripheral dispersal of Nissl substance, central granular zone) as well as abnormal nucleolar changes and dissociation of ribosomes from endoplasmic reticulum cisternae. Some satellite cells undergo retraction or acute degeneration, leaving only basement membrane to cover the neuron in these areas. 8 days after irradiation, neurons also exhibit (a) areas in which ribosomes are substantially reduced, (b) regions of cytoplasmic sequestration, (c) extensive vacuolization of granular endoplasmic reticulum and Golgi complex, and (d) diversely altered mitochondria (including the presence of ribosome-like particles or association with abnormal glycogen and lipid deposits). Nucleolar components become altered or reoriented and may form abnormal projections and ringlike configurations. Sizeable areas of the neuronal soma are now denuded of satellite cells; underlying these areas, nerve processes are found abnormally invaginated into the neuronal cytoplasm. By the 14th day following irradiation, most neurons display marked degenerative changes including extensive regions of ribosome depletion, sequestration, vacuolization, autolysis, and, in some areas, swirls of filaments, myelin figures, and heterogeneous dense bodies. These observations demonstrate that X-irradiation produces profound cytopathological changes in nervous tissue isolated from the host and that many of these changes resemble the effects of radiation on nervous tissue in vivo.