All the mammalian cells should require some machinary for the intracellular transport, and it seems essential to elucidate the mechanisms underlying this transport system in order to understand the functions of lipids. However, little is known about their mechanisms, possibly because of lack in the appropriate experimental techniques. Recently, the pathogenesis of some genetic diseases which originate from the defect of intracellular transport system have been elucidated, and these studies provides us important information on the physiologic role of lipid transport system. Here, recent progress on the intracellular lipid transport system, especially those of cholesterol, fatty acid, vitamin E and phospholipids are described.

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12 Wistar rats were fed with hypercholesterol chow and with hypercholesterol and Probucol chow for 3 to 6 months.
According to biochemical examination of serum obtained, Probucol did not have a suppressive effect on the concentration of cholesterol in rats, unlike other experimental animals and human.
In order to clarify the effect of Probucol on the vascular cells and Mato's FGP cells under hypercholesterolemia, the thoracic aorta, coronary arteries and microvessels of the cerebral cortex, including Mato's FGP cells were studied using a histochemical technique and electron microscopes.
Different from normal rats, in the hypercholesterol chow group, the endothelium of the thoracic aorta and coronary arteries were deformed and showed increase of electron opacity. Smooth muscle cells were irregular in shape and dark. Some of them suffered degeneration and their cytoplasmic organelles were dispersed in the muscle layer. The elastic laminae between the endothelium and muscle layer were occasionally disrupted. In cerebral microvessels, cytoplasmic projections of endothelial cells were often observed, and their electron opacity was enhanced. Irregularly shaped smooth muscle cells were arrayed underlying endothelial cells. Mato's FGP cells, external to the cerebral microvessels, frequently showed the fragility of, and damage to the cytoplasmic membrane, and showed complete degeneration.
In rats fed with hypercholesterol and Probucol chow, the morphological changes including degeneration of smooh muscle cells and disruption of elastic laminae, occurred in the thoracic aorta and coronary arteries. Such changes were similar to those in the hypercholesterol chow group. However, regarding cerebral microvessels, although the FGP cells incorporated a large amount of cholesterol, and represented large honeycomb-like inclusions, their profiles appeared normal, and possessed deep infoldings of the cytoplasmic membrane. No degeneration of FGP cells was detected in this experiment.
From the findings mentioned above, Probucol is a suitable drug to maintain the function of FGP cells and the normal architecture of cerebral microvessels even under marked hypercholesterolemia.
Finally, some possible mechanisms for the beneficial effect of Probucol to FGP cells and cerebral microvessels are discussed.

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Increased plasma level of lipoprotein (a) (Lp(a)) is associated with atherosclerosis and vascular disease. Though it is well known that there is a strong interaction between Lp(a) and resting platelets, there are no clinical studies on the relationship between Lp(a) and platelet adhesion and aggregation. We measured plasma Lp(a) concentration and platelet function in 103 normal volunteers. Small aggregations of platelets that formed spontaneously (SAG) were measured using laser light scattering. Platelet aggregation was measured by Borns method using epinephrine or ADP as an aggregate. There was no significant difference between HLP (subjects with LP(a)>12mg/dl) and LLP (Lp(a)<12mg/dl) by age, mean blood pressure, body mas index, blood glucose, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol concentrations, prothrombin time, activated partial thromboplastin time, fibrinogen or platelet counts. SAG was significantly higher in HLP than in LLP (p=0.0091). There was no significant difference between HLP and LLP in platelet aggregation when either epinephrine or ADP was used as an aggregate. Log (Lp(a)) correlated with log (SAG) positively (r=0.3116, p=0.001). SAG was inhibited by monoclonal anti glycoprotein IIb/IIIa complex anti body. We concluded that platelet glycoprotein and adhesion may contribute to the relationship between Lp(a) and atherosclerosis.

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This multi-institutional co-operative study examined the preventive effect of niceritrol on arteriosclerotic diseases. Patients with hyperlipidemia (serum cholesterol above 220mg/dl and/or triglyceride above 150mg/dl) or low HDL-cholesterol (7lt;45mg/dl for males and7lt;50mg/dl for females) were enrolled into the study and they were divided into two groups, i. e. control group (n=382) and niceritrol group (n=661). In the niceritrol group, an anti-lipidemic agent (nicotinic acid derivative, niceritrol 750mg per day) was administrated, and in the control group, administration of any kind of anti-lipidemic agents was prohibited. Serum lipids and ECG recordings were examined regularly during the study period in both group.
The results showed that serum total cholesterol, triglycerides and LDL-cholesterol decreased significantly and HDL-cholesterol increased significantly from the baseline in the niceritrol groups while there were no significant changes of serum lipids observed in the control.
Improvement rate of Ischemic ECG changes during the study period was significantly greater in the niceritrol group (26.0%) than in the control group (2.9%) (p<0.05).
These results indicate the benefical effect of niceritrol in the treatment of Ischemic heart disease via amelioration of hyperlipidemia.

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Antihyperlipidemic effect of cholestenone (cholest-4-en-3-one), an intestinal catabolite of cholesterol, was investigated by 1% dietary exposure in three Watanabe heritable hyperlipidemic (WHHL) rabbits which are models of familial hypercholesterolemia. Animals were fed standard chow diet for 2 weeks, 1% cholestenonesupplemented diet for 3 weeks, followed by a standard chow diet for 2 weeks. When animals were fed the cholestenone-supplemented diet, serum cholesterol levels decreased progressively from about 700 to about 470 mg/dl during the 3 weeks, and serum triglyceride levels dropped rapidly from about 360 to about 50mg/dl by 1 week. The reduced levels of serum triglyceride were maintained for the next 2 week. After cessation of cholestenone, the amounts of serum cholesterol in 2 animals and triglyceride in all animals rose progressively to the previous levels. There were few differences in phospholipids levels in the serum of animals fed cholestenone. Body weight gain, food consumption and food efficiency of animals were inhibited by dietary exposure to this chemical. There were no obvious abnormalities due to consumption of cholestenone on clinical observation.

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