The presence of apolipoproteins A-I, E, C-II, and GIII and the absence of apolipoprotein B was demonstrated in human cerebrospinal fluid. The concentration of apolipoproteins was measured by electroimmunoassay. Apolipoproteins E, C-I1, and C-Il were present in cerebrospinal fluid at 3-5% of their concentration in plasma; the cerebrospinal fluid level of apolipoprotein A-I was 0.4%. Most of the cerebrospinal fluid apolipoproteins were present in the p < 1.21 g/ml i protein fraction. The major apoli proteins of cerebrospinal fluid are E and A-I. The possible mechanism of transfer and the physiological and pathophysiological role of apolipoproteins in cerebrospinal fluid are postulated.Lipoproteins are macromolecular complexes with Mrs ranging from 107 for very low density lipoproteins (VLDL), 2-3 X 106 for low density lipoproteins (LDL), and 2-4 X 105 for high density lipoproteins (HDL) (1, 2). The protein moieties of the lipoproteins, the apolipoproteins (apo), have specific physiological functions, and some of their alterations are associated with pathological conditions (1-3). The enzyme lecithin cholesteryl acyltransferase requires the presence, as a cofactor, of apo A-I which has a Mr of 28,000 (1, 2). Recently, a cholesteryl ester transfer protein has been described and it is thought to be one of the minor apos, apo D (Mr, 22,000) (4). The action of lipoprotein lipase is modulated by the apo Cs which have Mrs of approximately 000 (1, 2). Cellular cholesterol metabolism is regulated by apo B (Mr, 260,000) and apo E (Mr) 33,000) (1, 2,5, 6).Because interstitial fluid is in direct contact with the cell, knowledge of its apo composition and concentration is important in understanding the regulation of cellular lipid metabolism. Lipoprotein and apo profiles of plasma are being extensively investigated, but information on the apo composition of interstitial fluid is sparse. Apo B concentration in human peripheral lymph is 10% of its concentration in plasma (7) and it is biologically active at that concentration (8). It has been postulated that apos are present in the circulation not only as part of the lipoprotein particle but also as "free" apos-i.e., not associated with a conventional lipoprotein particle (9). Studies with rat renal lymph have shown that its apo composition is different from that in plasma but it is similar to the apo composition of the lipoprotein-free p > 1.21 g/ml fraction (10).The dominant process in the formation of interstitial fluid is filtration of plasma. The concentrations of macromolecules in the interstitial fluids, lymph, and cerebrospinal fluid are inversely related to their Mr (11). Because the permeability of the blood cerebrospinal fluid barrier is much more restricted than the permeability of peripheral capillaries, we chose to examine whether apos are present in cerebrospinal fluid as an approach to the molecular form in which apos are transferred. METHODSCerebrospinal fluid was collected from patients undergoing myelography. Unconcentrated fluid was used for determi...

Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All meals and snacks, except Saturday dinner, were prepared and served by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximately 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant in most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced. In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population.

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Abstract-High density lipoproteins (HDLs) and their subspecies play a role in the development of coronary heart disease (CHD). HDL subpopulations were measured by 2-dimensional nondenaturing gel electrophoresis in 79 male control subjects and 76 male CHD patients to test the hypothesis that greater differences in apolipoprotein (apo)A-I-containing HDL subpopulations would exist between these 2 groups than for traditional lipid levels. In CHD subjects, HDL cholesterol (HDL-C) was lower (Ϫ14%, PϽ0.001), whereas total cholesterol and the low density lipoprotein cholesterol/HDL-C ratio were higher (9% [PϽ0.05] and 21% [PϽ0.01], respectively) compared with control levels. No significant differences were found for low density lipoprotein cholesterol, triglyceride, and apoA-I levels. In CHD subjects, there were significantly (PϽ0.001) lower concentrations of the large lipoprotein (Lp)A-I ␣ 1 (Ϫ35%), pre-␣ 1 (Ϫ50%), pre-␣ 2 (Ϫ33%), and pre-␣ 3 (Ϫ31%) subpopulations, whereas the concentrations of the small LpA-I/A-II ␣ 3 particles were significantly (PϽ0.001) higher (20%). Because ␣ 1 was decreased more than HDL-C and plasma apoA-I concentrations in CHD subjects, the ratios of HDL-C to ␣ 1 and of apoA-I to ␣ 1 were significantly (PϽ0.001) higher by 36% and 57%, respectively, compared with control values. Subjects with low HDL-C levels (Յ35 mg/dL) have different distributions of apoA-I-containing HDL subpopulations than do subjects with normal HDL-C levels (Ͼ35 mg/dL). Therefore, we stratified participants according to HDL-C concentrations into low and normal groups. The differences in lipid levels between controls and HDL-C-matched cases substantially decreased; however, the significant differences in HDL subspecies remained. Our research findings support the concept that compared with control subjects, CHD patients not only have HDL deficiency but also have a major rearrangement in the HDL subpopulations with significantly lower ␣ 1 and pre- Key Words: HDL subpopulations Ⅲ coronary heart disease Ⅲ lipids Ⅲ lipoproteins Ⅲ apolipoproteins C oronary heart disease (CHD) remains the leading cause of death and disability in the United States. Approximately 14 million people have CHD, and 1.5 million individuals experience a myocardial infarction annually, leading to Ϸ500 000 deaths per year. 1 Atherosclerosis is a multifactorial disease affected by lifestyle and genetic factors. 2 Independent risk factors for CHD as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel II include the following: age, sex, hypertension, smoking, diabetes, family history of premature CHD, elevated plasma levels of LDL cholesterol (LDL-C Ն160 mg/dL), and low levels of HDL (HDL-C Ͻ35 mg/dL). 3-10 The NCEP panel classified an HDL-C level Ն60 mg/dL (Ͼ1.55 mmol/L) as protective against the development of CHD. 3 Many prospective epidemiological studies have indicated that a decreased HDL-C level is a significant independent risk factor for heart disease. [5][6][7]9,11,12 HDL is found in human plasma at a density of 1.063 t...