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J D Morrisett

Publications and source records attributed to J D Morrisett.

At least 19 recordsLinked to original sources
PubMed1992

Triglyceride metabolism in 3T3-L1 cells. An in vivo 13C NMR study.

13C nuclear magnetic resonance spectroscopy has been used to study triglyceride metabolism in 3T3-L1 cells incubated with [1-13/14C] acetate, myristate, palmitate, stearate, or oleate. Labeled cells embedded in agarose filaments were perfused in a specially fitted NMR tube within the spectrometer magnet. Incubation of 3T3-L1 cells with a specific fatty acid enriched the cellular triglycerides with that fatty acid; the NMR signal observed in the carbonyl region of the cell spectrum was due in large part to that fatty acid. NMR data demonstrated that cellular enzymes preferentially esterified saturated fatty acids at the glyceride sn-1,3 position and unsaturated fatty acids at the sn-2 position. cellular triglyceride hydrolysis by hormone-sensitive lipase was monitored by measuring the decrease in the integrated intensities of resonances arising from fatty acyl carbonyls esterified at glycerol carbons sn-1,3 and sn-2. Under basal conditions, the time courses were first-order, and the average rates were 0.14% of signal/min at both carbonyl positions. Under isoproterenol stimulated conditions, these rates were still first-order and increased 6.4-fold at the sn-1,3 position and 2.4-fold at the sn-2 position. The observation that the hydrolysis time courses were first-order suggested that only a small amount of cellular triglyceride was available to hormone-sensitive lipase, supporting the view that lipolytic enzymes operate at lipid surfaces where only small amounts of neutral lipid may be soluble. Attempts to correlate the measured rates with the rates of hydrolysis at the sn-1,3 and sn-2 positions were hindered by the fact that the chemical shifts of the carbonyl carbons of the diglyceride hydrolysis product did not overlie those of the triglyceride. Analysis of hydrolysis kinetics revealed that hormone-sensitive lipase exhibited little preference for a particular esterified fatty acid under basal conditions; however, under stimulated conditions, the enzyme exhibited a preference for certain triglyceride species.

3T3 Cells↗
PubMed1992

A structural assessment of the apo[a] protein of human lipoprotein[a].

Apolipoprotein[a], the highly glycosylated, hydrophilic apoprotein of lipoprotein[a] (Lp[a]), is generally considered to be a multimeric homologue of plasminogen, and to exhibit atherogenic/thrombogenic properties. The cDNA-inferred amino acid sequence of apo[a] indicates that apo[a], like plasminogen and some zymogens, is composed of a kringle domain and a serine protease domain. To gain insight into possible positive functions of Lp[a], we have examined the apo[a] primary structure by comparing its sequence with those of other proteins involved in coagulation and fibrinolysis, and its secondary structure by using a combination of structure prediction algorithms. The kringle domain encompasses 11 distinct types of repeating units, 9 of which contain 114 residues. These units, called kringles, are similar but not identical to each other or to PGK4. Each apo[a] kringle type was compared with kringles which have been shown to bind lysine and fibrin, and with bovine prothrombin kringle 1. Apo[a] kringles are linked by serine/threonine- and proline-rich stretches similar to regions in immunoglobulins, adhesion molecules, glycoprotein Ib-alpha subunit, and kininogen. In comparing the protease domains of apo[a] and plasmin, apo[a] contains a region between positions 4470 and 4492 where 8 substitutions, 9 deletions, and 1 insertion are apparent. Our analysis suggests that apo[a] kringle-type 10 has a high probability of binding to lysine in the same way as PGK4. In the only human apo[a] polymorph sequenced to date, position 4308 is occupied by serine, whereas the homologous position in plasmin is occupied by arginine and is an important site for proteolytic cleavage and activation. An alternative site for the proteolytic activation of human apo[a] is proposed.

Amino Acid Sequence↗
PubMed1992

Method for calculating 3-D coordinates from molecular stereograms.

The three-dimensional coordinates for the alpha-carbon atoms of crambin and basic pancreatic trypsin inhibitor (BPTI) were determined from the respective alpha-carbon trace stereograms using an improved Simplex algorithm. This algorithm was used in a two-step process to estimate the z-coordinate values. In one approach, an average interatomic distance value, an approximate viewing angle, and a table of digitized values for xleft, yleft and xright, yright are provided in the first step. In the second step, the z-coordinate values are derived by varying z to minimize the bond distance error (Rossmann and Argos, 1980). In another approach, only a reference bond distance table is provided along with the table of xleft, yleft and xright, yright digitized values. In the first step, the viewing angle (phi), a combined scale and viewing distance parameter (q), a rotational angular distortion from digitizing and/or photocopying (z), and translational distortion factors (xerr and yerr) are calculated. In the second step, the z-coordinate values are varied to minimize the bond distance error. RMS difference values of less than 1.5 A were obtained for both crambin and BPTI alpha-carbon atoms.

Algorithms↗
PubMed1992

Proceedings of a National Cancer Institute workshop: MR spectroscopy and tumor cell biology.

In December 1991, the National Cancer Institute held a workshop to evaluate the role of magnetic resonance (MR) spectroscopy in human cancer biology. The clinical and basic cancer research issues requiring use of MR spectroscopy, the advantages and limitations of MR spectroscopy, and future directions in MR spectroscopy of cancer were discussed. Consensus-building panels were formed on the following four topics: cell membrane biochemistry, tumor therapeutic response or drug resistance, appropriate model systems, and potential clinical applications of MR spectroscopy. The workshop members concluded that large prospective clinical studies as well as in vivo animal and human studies to define prognostic variables should be performed, with correlation between MR spectroscopic results and biochemical and physiologic features. Studies of phospholipid metabolism, the pharmacokinetics of anticancer agents, and effects of new cancer treatments on the tumor vasculature and normal tissues are needed.

Humans↗
PubMed1992

Sialic acid content of human low density lipoproteins affects their interaction with cell receptors and intracellular lipid accumulation.

Low density lipoproteins (LDL) isolated from the plasma of patients with angiographically demonstrable coronary heart disease (CHD) induced accumulation of triglycerides, free cholesterol, and cholesteryl esters in cultured macrophages, smooth muscle cells, and endothelial cells derived from uninvolved intima of human aorta, but not in skin fibroblasts or hepatoma cells. The sialic acid content of LDL from CHD patients was 40-75% lower than that from healthy donors. There was a negative correlation between LDL sialic acid content and the LDL-induced accumulation of total intracellular cholesterol. Neuraminidase treatment of LDL from normal healthy donors produced sialic acid-depleted LDL (Ds-LDL) which was able to stimulate intracellular lipid accumulation. Neuraminidase treatment of LDL from CHD patients further increased its capacity to induce intracellular lipid accumulation. Sialic acid-poor LDL isolated by affinity chromatography of LDL from CHD patients induced a 2- to 4-fold increase of free and esterified cholesterol in human intimal smooth muscle cells. Binding, uptake, and degradation of 125I-labeled Ds-LDL by macrophages and endothelial cells were 1.5- to 2-fold higher than for native LDL. Binding and uptake of Ds-LDL was inhibited 64-93% by the addition of 20-fold excess acetylated LDL (Ac-LDL); in the inverse experiment, the level of inhibition was 35-54%. These data indicate that a sialic acid-poor form of LDL isolated from CHD patients can interact with both native and scavenger LDL receptors. A sialic acid-poor form of LDL may be a naturally occurring ligand that interacts with the scavenger receptor(s) on macrophages and endothelial cells.

Adult↗
PubMed1991

13C NMR spectroscopic analysis of phospholipid metabolism in adrenal chromaffin cells.

Phosphatidylcholine (PC) metabolism in bovine adrenal chromaffin cells has been studied in vivo with 100 MHz 13C NMR spectroscopy. The incorporation of 13[CH3]choline was examined in cells embedded in 1% agarose strands and perfused at 37 degrees C. The pattern of 13C NMR spectroscopy. The incorporation of [13CH3]choline incorporation into PC of suspension cultures of chromaffin cells. The chemical shifts of labelled carbons in [13CH3]choline before and after their incorporation into PC are identical (ca 56.4 ppm). Incorporated [13CH3]choline can be released from the cells by phospholipase D which reduces the cellular PC signal by greater than 85%, indicating that a major fraction of the labelled PC is on the external membrane surface. This application of NMR spectroscopy provides a basis for direct measurement of the in vivo metabolism of PC in functioning adrenal chromaffin cells.

Adrenal Glands↗
PubMed1991

Cholesterol metabolism in hypercholesterolemia-resistant rabbits.

Normal rabbits typically respond to a diet high in cholesterol with a large increase in the concentration of plasma cholesterol. We have previously described the breeding and partial characterization of a variant rabbit which does not respond to a high cholesterol diet with changes in plasma cholesterol concentration. In the present report we have characterized three components involved in cholesterol homeostasis: the B/E (LDL) receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity (HMG-CoA reductase, EC 1.1.1.34) and acyl-coenzyme A: cholesterol acyltransferase activity (ACAT, EC 2.3.1.26) in the livers of the hypercholesterolemia-resistant rabbits. Using normal cholesterol-fed rabbit [125I] beta-VLDL as a ligand, liver membranes prepared from resistant rabbits fed a low-cholesterol diet had 70% higher binding capacity than membranes from normal rabbits fed the same diet. Similar experiments demonstrated that the resistant rabbits had a 240% higher B/E receptor binding capacity compared to normal animals when liver membranes were prepared from animals fed a 0.25% cholesterol-enriched diet. No difference in the binding affinity of [125I]beta-VLDL was detected in membranes prepared from normal or resistant animals. When fed a low-cholesterol diet, the resistant rabbits had approximately 2-fold higher hepatic HMG-CoA reductase activity (97.4 +/- 3.5 pmol product/mg/min in resistant animals compared to 45 +/- 1.1 pmol product/min/mg in normal animals). The difference was exaggerated in animals fed the 0.25% cholesterol-enriched diet, 73.3 +/- 5.5 vs 2.4 +/- 0.56 pmol product/min/mg for resistant and normal membranes respectively. The basal activity of ACAT in hepatic membranes was significantly lower in the resistant rabbits compared to normal rabbits (138 +/- 11 vs 268 +/- 19 pmol cholesteryl ester/min/mg in resistant and normal rabbits respectively); when fed a 0.25% cholesterol-enriched diet, the enzyme was induced 6-fold in normal animals but was increased only 2-fold in the resistant animal. These biochemical data suggested that the resistant rabbit maintained low intracellular cholesterol even when fed a cholesterol-enriched diet. Direct measurement of cellular cholesterol and cholesteryl esters demonstrated that the concentration of these lipids was significantly lower in the resistant animal than in normal animals with the largest differences found in the cytoplasmic rather than the membrane compartment. These studies demonstrate that the resistant rabbit manifests several quantitative differences in cholesterol metabolism and in the regulation of cholesterol metabolism; but these studies do not directly explain the underlying cause of the resistance to hypercholesterolemia in the resistant rabbit.

Animals↗
PubMed1991

Lipoprotein(a) and apolipoprotein changes after cardiac transplantation.

Although lipoprotein changes after cardiac transplantation have been documented, the effects of transplantation and subsequent immunosuppressive therapy (particularly the combination of prednisone, azathioprine and cyclosporine) on apolipoprotein levels and lipoprotein(a) have not been reported. Fasting cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein A-1 and B-100 and lipoprotein(a) were evaluated in 69 consecutive patients during the waiting period before cardiac transplantation. There were 28 deaths before donor organ identification and 41 patients received a cardiac allograft. The lipoprotein levels of transplant recipients were again assayed 3 months postoperatively. Mean (+/- SEM) values increased for total plasma cholesterol (from 180 +/- 8 to 228 +/- 8 mg/dl, p less than or equal to 0.001), triglycerides (from 126 +/- 11 to 207 +/- 14 mg/dl; p less than or equal to 0.001), HDL cholesterol (from 39 +/- 2 to 49 +/- 3 mg/dl; p less than or equal to 0.002) and LDL cholesterol (from 119 +/- 7 to 138 +/- 7 mg/dl; p less than 0.02). Apolipoprotein A-1 and B-100 also increased, but lipoprotein(a) decreased from 11.7 +/- 1.7 to 6.8 +/- 1.1 mg/dl; p less than or equal to 0.0001) after transplantation. Although total cholesterol, triglycerides, LDL cholesterol, apolipoprotein A-1 and B-100 increased dramatically after cardiac transplantation, so did HDL cholesterol, thereby keeping the LDL/HDL cholesterol ratio constant. The surprising decrease in lipoprotein(a) after cardiac transplantation suggests that metabolism of lipoprotein(a) is independent of LDL cholesterol and that immunosuppressive drugs either decrease the synthesis or increase catabolism of lipoprotein(a).

Apolipoproteins↗
PubMed1991

Amino acid sequence of rabbit apolipoprotein E.

The complete amino acid sequence of rabbit apolipoprotein E (apoE) was determined by generating three sets of peptides using cyanogen bromide, endoproteinase AspN, and Staphylococcus aureus V8 protease to cleave the protein. Through twenty cycles of sequence analysis on the whole protein, glutamic acid was identified as the N-terminal residue of rabbit apoE; the C-terminus of the protein was identified as glutamine. Based on the sequence of 294 amino acid residues determined by protein structure analysis, the molecular weight of rabbit apoE was determined to be 33,684. The protein sequence differed from the cDNA inferred sequence in 19 positions, only one of which could be attributed to microheterogeneity. The corrected amino acid sequence of rabbit apoE shares 80% homology with the human apoE sequence, 4% greater homology than that inferred from the cDNA sequence. The great similarity in the amino acid sequences of human and rabbit apoE suggests that their physical and physiological properties may also be similar. This homology and the relative ease with which apoE is isolated from rabbit plasma make it possible to conduct some in vitro experiments with the rabbit apoprotein that would have direct relevance to human apoE, but would be difficult or impossible with the human counterpart because of the quantity of protein required.

Amino Acid Sequence↗
PubMed1990

Effect of particle size and temperature on the conformation and physiological behavior of apolipoprotein E bound to model lipoprotein particles.

The effect of particle size and structural order/disorder of the lipid domain on the conformation and physiological behavior of lipid-associated apolipoprotein E (apoE) was evaluated. Circular dichroic (CD) spectra of apoE bound to large (LME) and small (SME) microemulsion particles, composed of dimyristoylphosphatidylcholine (DMPC) and cholesteryl oleate (CO), and to DMPC disks revealed that at 4 degrees C, where all of the lipid constituents were in an ordered state, apoE bound to LME displayed approximately 60% alpha-helicity, while apoE bound to SME and DMPC disks displayed 73% and 95% helicity, respectively. Over the temperature range 4-50 degrees C, encompassing the lipid thermal transitions, only apoE bound to LME demonstrated an abrupt change in its CD spectrum (decrease in alpha-helicity) in response to temperature. To determine the source of the abrupt CD change, the constants for dissociation (Kd) of apoE from the surface of the large and small microemulsion particles were determined at 4, 25, and 37 degrees C. These results demonstrated that at 4 degrees C, the KdS for binding of apoE to the LME and SME were approximately equal; however, between 4 and 25 degrees C, there was a 5-fold increase in the Kd for binding of apoE to the LME, whereas the Kd for binding to the SME remained constant. The physiological effects of these differences in apoE secondary structure and equilibrium binding were examined by measuring the capacity of each apoE-containing particle to complete with LDL for binding to human fibroblasts, and by measuring the capacity of the apoE-microemulsion particles to suppress HMG-CoA reductase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins E↗
PubMed1990

Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.

Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.

Acetylcholine↗
PubMed1990

Cyclopentanoid analogs of dipalmitoyl phosphatidic acid: effect of backbone geometry on thermotropic properties.

Seven geometrical or positional isomers of dipalmitoyl cyclopentanophosphoric acid (DPCPA) have been synthesized and studied: 1,3/2-1P (I); 1,2/3-1P (II); 1,2/3-3P (III), 1,2,3/0-1P (IV); 1,2,3/0-2P (V); 1,3/2-2P (VI); 1,2/3-2P (VII). When dispersed in 0.1 M Tris-HCl at pH 7.4, I-VII gave thermal transitions (Tc) of 60.0 degrees, 59.0 degrees, 56.8 degrees, 55.3 degrees, 38.3 degrees, 36.8 degrees and 34.0 degrees C, respectively, as measured by differential scanning calorimetry (DSC). When the lipids were dispersed at pH 9.5 in 0.1 M borate, Tc of I-IV decreased, whereas Tc of V-VII increased. In contrast, at pH 1.5 in 0.1 M HCl/KCl, Tc of I-IV decreased slightly, but Tc of V-VII rose markedly. To determine the effect of head group geometry and substitution pattern on acyl chain motion, EPR spectra of 1-palmitoyl, 2-[16-doxylstearoyl]-glycero-3-phosphoric acid in bilayers of DPCPA isomers were acquired. Abrupt spectral changes occurred at temperatures closely correlating with transition temperatures observed by DSC. These results have led to the conclusions that: (i) isomers I-IV containing vicinal acyl chains form bilayers that exhibit structural transitions at temperatures higher than those at which transitions are exhibited by isomers V-VII which have a polar phosphate group interposed between the two chains; (ii) the effects of differences in backbone structure are transmitted down the entire length of the acyl chains; (iii) the orientation of the cyclopentane ring in the isomers I-IV is significantly different from that in isomers V-VII at pH values where the phosphate group is doubly negatively charged.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

A technique for flow-enhanced magnetic resonance angiography of the lower extremities.

A two-dimensional, flow-enhanced gradient echo pulse sequence for nuclear magnetic resonance angiography is described. It employs interleaved, presaturated slices to acquire data efficiently on imagers which favor interleaved acquisition over sequential acquisition for multislice imaging. It is useful on any imagers when the effective TR is extended to enhance the sensitivity to slow flow. The technique was applied to the region from aortic bifurcation to the iliac bifurcations of three normal volunteers. The right and left common iliac arteries and veins, the separation of the external and internal iliac arteries, and secondary branches were clearly depicted.

Blood Vessels↗
PubMed1990

Dietary cholesterol absorption, and sterol and bile acid excretion in hypercholesterolemia-resistant white rabbits.

The New Zealand white (NZW) rabbit fed a 0.1% cholesterol-enriched diet (CD) typically responds (normoresponsive, NR) by quickly developing hypercholesterolemia. To study the underlying mechanisms responsible for the widespread phenomenon of inter-individual variability of response to dietary cholesterol, a unique hypercholesterolemia-resistant (RT) rabbit model was developed. These animals were utilized to investigate selected potential mechanisms that might enable the RT animal to compensate for dietary cholesterol overload. When rabbits were fed the low-cholesterol stock diet, there was no significant difference in the plasma cholesterol concentrations of the NR and the RT animals. However, a significant rise was observed in the NR rabbits within 1 month of their being placed on the cholesterol-enriched diet; the plasma cholesterol concentration of the RT animals was not affected. During consumption of the cholesterol diet the cholesterol absorption rate was somewhat greater in the NR rabbits (P less than 0.05), whereas intestinal transit times and the fecal excretion of neutral steroids were substantially the same in both groups. In contrast, the fecal bile acid excretion of the RT animals was more than twice as great (P less than 0.0001) as that of the NR animals. We conclude that the response to dietary cholesterol is a heritable trait in these rabbits and that, although less dietary cholesterol was absorbed by the RT animals, it appears that a major mechanism controlling plasma cholesterol levels involves the rate of conversion of cholesterol to bile acids and their subsequent excretion.

Animals↗
PubMed1990

Polymorphic forms of human apolipoprotein[a]: inheritance and relationship of their molecular weights to plasma levels of lipoprotein[a].

The plasma concentration of human lipoprotein[a], Lp[a], is highly correlated with coronary artery disease. The protein moiety of Lp[a], apoLp[a], consists of two apoproteins, apo[a] and apoB-100, linked by one or more disulfide bonds(s). Apo[a], the protein unique to Lp[a], exists in polymorphic forms that exhibit different apparent molecular weights (Mr). Polyacrylamide gel electrophoresis in sodium dodecyl sulfate followed by immunoblotting was used to separate and visualize these different forms and to determine the polymorphic pattern of apo[a] in the plasma samples of 692 individuals. A total of 11 different polymorph bands ranging in Mr from 419 kD to 838 kD could be resolved, but only 1 or 2 bands were present per individual. The polymorphic band pattern for an individual was assigned to 1 of the 66 different phenotype designations representing the total number of possible single- and double-band combinations of the 11 detectable bands. All 11 of the possible single-band phenotypes but only 32 of the 55 possible double-band phenotypes were represented. There were 412 plasma samples (59.5%) that contained a single band, 274 (39.6%) contained two bands, and only 6 (0.9%) had no detectable apo[a] band. A highly significant inverse correlation was found between the Mr of the band(s) present and the plasma apoLp[a] concentration (r = -0.461; rho = 0.0001). The correlation was better between apoLp[a] and single-band (r = -0.495; rho = 0.0001) than double-band (r = -0.382; rho = 0.0001) phenotypes. Of the 274 individuals exhibiting double-band phenotypes, the lower Mr band was more intense in 141 (51.4%), the two bands were equally intense in 85 (31.0%), while the higher Mr band was more intense in 48 (17.5%). Based upon the hypothesis that apo[a] polymorphism is controlled by different alleles at a single locus, the frequency of the 11 alleles determined from the observe phenotypes (low Mr----high Mr) was: band 1) 419 kD, 0.00875; band 2) 489 kD, 0.00510; band 3) 536 kD, 0.0555; band 4) 553 kD, 0.0758; band 5) 613 kD, 0.135; band 6) 680 kD, 0.0824; band 7) 705 kD, 0.104; band 8) 742 kD, 0.151; band 9) 760 kD, 0.246; band 10) 796 kD, 0.128; band 11) 838 kD, 0.00802. The observed distribution of phenotypes in the population was compared by chi-square analysis to that predicted on the basis of simple Mendelian inheritance, and the hypothesis was rejected (chi 2 = 921.7; rho less than 0.001). Significantly, the singleband phenotypes are over-represented in the population compared to that predicted.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoproteins A↗
PubMed1990

Cholesterol metabolism in fibroblasts from rabbits resistant to diet-induced hypercholesterolemia.

We have previously described a colony of New Zealand White rabbits that are resistant to hypercholesterolemia when fed a cholesterol-enriched diet. The present studies used skin fibroblasts obtained from normal and hypercholesterolemia-resistant rabbits to investigate cholesterol metabolism and lipid composition in vitro. The lipid compositions of the two cell lines after incubation in either fetal calf serum or lipoprotein-deficient serum were similar. The conversion of radiolabeled acetate into sterol and phospholipids was higher in resistant fibroblasts than in normal fibroblasts. In contrast, incorporation of radiolabeled oleic acid into cholesteryl ester was significantly lower in resistant fibroblasts than in normal cells. In parallel experiments, the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was higher and acyl-coenzyme A:cholesterol acyltransferase activity was lower in resistant cells compared to normal cells. Furthermore, binding, uptake, and degradation of normal rabbit 125I-labeled LDL (low density lipoproteins) were 30% higher in resistant than in normal fibroblasts. These observations are consistent with results from previous studies of cholesterol metabolism in the liver membranes of these rabbits. The results indicate that extrahepatic cells (such as fibroblasts) from the resistant rabbit exhibit the same altered cholesterol metabolism as that found in the hepatic tissues of these rabbits. These studies suggest that the resistant rabbit may provide an in vivo and in vitro system for studying the mechanisms by which some individuals of a species can minimize the effect of dietary cholesterol on the development of hypercholesterolemia and atherosclerosis.

Animals↗