Lipid Atherosclerosis Research Articles

Founding, early history, and transformation of the Journal for Lipid Research to an American Society of Biochemistry and Molecular Biology journal

The Journal of Lipid Research was founded in October, 1959 and has had a long and distinguished history. It evolved from an initial concept of a loose-leaf methodology handbook to a major journal for the lipid field. Its growth has in many ways paralleled the growth and expansion of lipid research. Today, it is operated as a journal of the American Society for Biochemistry and Molecular Biology at the forefront of biomedical research on lipids.

Independent Effect of Cardiac Rehabilitation on Lipids in Coronary Artery Disease

Independent Effect of Cardiac Rehabilitation on Lipids in Coronary Artery Disease

Independent Effect of Cardiac Rehabilitation on Lipids in Coronary Artery Disease

We evaluate the effects cardiac rehabilitation (CR) participation independent of using lipid-altering agents (LAAs) on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol, and triglyceride. Measurements included absolute and relative change in lipids and increases in percent of patients achieving goals. Analysis of 766 patients who participated in CR between 2000 and 2003 was performed. On enrollment to CR, all were being treated with an LAA defined as HIviG-CoA reductase inhibitors, bile acid sequestrant, fibrate, and niacin, hormone replacement therapy. Preenrollment and postenrollment lipids were obtained. Analysis was performed on 2 cohorts, participants enrolled on an LAA with no change in medication (n = 13) and participants enrolled on an LAA with a change in medications (n = 153). At completion of CR, 74.9% of patients on LAA at enrollment with no medication adjustments during the program were at Adult Treatment Panel III goal for low-density lipoprotein cholesterol compared with 68.5% at entry (P = .01), all other lipid parameters also significantly improved. Sixty-three percent who started CR on an LAA and had dose adjustment or an additional LAA added achieved low-density lipoprotein cholesterol goal compared with 43.1% at entry (P < .0001). Participation in CR significantly potentiates the lipid-improving effects of pharmacological therapy and independently contributed to the percent of patients achieving all lipid levels at Adult Treatment Panel III goal.

Blood Lipids: A Shortcut From Hostility to Chd?

The present article describes the associations between hostility and serum lipids in Coronary Artery Disease (CAD) patients. A sample of 212 male coronary patients was used of which 127 recently suffered a Myocardial Infarction (MI), and 85 had undergone either a Coronary Artery Bypass Grafting (CABG) or a Percutaneous Transluminal Coronary Angioplasty (PTCA). Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and triglyceride concentrations were measured as well as four hostility factors: ‘Negative Affectivity’ (NA), ‘Anger-In’ (AI), ‘Anger-Out’ (AO) and Coping, i.e. behaviors to control feelings of anger and anxiety. The results indicated that the effects of hostility on lipids were mediated by various factors such as body weight in relation to body length (BMI), Socio-Economic Status (SES), Left Ventricle Ejection Fraction (LVEF) and Age. In subgroups of highly exhausted patients or of patients scoring high on the Type A Behavior Pattern (TABP), however, more direct (unilinear) associations between lipids and hostility were found. The findings of the present study confirm the rather weak association between hostility and blood lipids found elsewhere. Furthermore, a low level of triglycerides was consistently associated with low AO, be it again in interaction with BMI (AO × BMI), both in the group of non-MI patients and in the total sample for those patients who score high on vital exhaustion and/or TABP. This finding provides an extra argument against the popular notion of the healthfulness under all circumstances of anger expression. Until now the exact role of triglycerides as a function of anger/hostility has been under-explored. This issue merits further attention in future research.

Statin Lipid-Lowering Therapy for Acute Myocardial Infarction and Unstable Angina: Efficacy and Mechanism of Benefit

The use of statin agents in patients with acute coronary syndromes (ACSs) remains an area of intense clinical interest. Statin therapy has an established secondary preventive benefit in patients with coronary artery disease, and its extension to ACS seems logical. A number of observational studies have shown an association between initiation of statin therapy early in ACS and improved clinical outcome. Additionally, 4 randomized controlled trials have examined the use of statin therapy for ACS: the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study, the Pravastatin Turkish Trial, the Fluvastatin on Risk Diminishing After Acute Myocardial Infarction (FLORIDA) study, and the Lipid-Coronary Artery Disease (L-CAD) study. Three of these trials showed a benefit with early initiation of statin therapy, whereas 1 trial demonstrated neither benefit nor harm. All the available trials lacked the power and design to sufficiently evaluate whether early initiation of statin therapy reduces mortality and reinfarction in patients with ACS. Four ongoing trials have been designed and sufficiently powered to determine whether statin therapy reduces the risk of death and reinfarction when initiated early in ACS treatment. A body of evidence suggests that the pleiotropic actions of statin agents might modulate benefit in ACS. This article summarizes the available data and provides a rationale for early initiation of statin therapy for patients with ACS.

Coronary Heart Disease, Hypercholesterolemia, and Atherosclerosis I. False Premises

Lipid-rich caseous debris of advanced lesions stimulated interest in the role of cholesterol and lipids in atherosclerosis. Lipid-containing arterial lesions in cholesterol-overfed animals (cholesterolosis) and xanthomatous vascular lesions in subjects with familial hypercholesterolemia were then misrepresented as being atherosclerotic and led to the development of the hypercholesterolemic/lipid hypothesis. It is untenable that cholesterol, an essential multifunctional metabolite, is pathogenic at all blood levels and hypercholesterolemia is not prerequisite for human or experimental atherosclerosis. Serum cholesterol levels display a poor correlation with atherosclerosis at autopsy and with unreliable national coronary heart disease (CHD) mortality in each sex. Atherosclerosis topography and its iatrogenic production in humans and experimentally in herbivores by hemodynamic means both support a biomechanical causation and preclude causality by any circulating humoral factor. CHD, not a specific disease, is a nonspecific complication of many diseases including atherosclerosis and cannot be equated with coronary atherosclerosis due to differences in pathology and pathogenesis. Thus, extrapolations from CHD risk factors or correlations with fallacious vital statistics to atherosclerosis are invalid. It follows that the hypercholesterolemic/lipid hypothesis evolving from false premises, misuse of CHD, scientific misrepresentation, and fallacious data has no legitimate basis.

Assessing Structure-Property Relations of Diseased Tissues Using Nanoindentation and FTIR

ABSTRACTDisease processes are often associated with changes in tissue composition. For example, in atherosclerosis lipid and calcification are often found in the artery wall, whereas in healthy arteries the tissue microstructure is dominated by highly organized collagen. Such variations in composition likely result in changes in the material properties of the tissue. However, this relationship has not been fully investigated in atherosclerotic vessels. Using a combination of nanoindentation and spectroscopic techniques, our goal was to assess how changes in tissue composition affect the tissue's mechanical properties. Fourier Transform Infrared Spectroscopy (FTIR) was used to assess the biochemical composition of the tissue samples, such as the lipid and calcium content of fibrous tissues in diseased arteries. Nanoindentation was used to measure the local mechanical properties of the same tissue samples. This information was then correlated by position in the sample to assess the contributions of different constituents to the overall structure-property relations of these tissues.

Gender and lipids in coronary artery disease

Gender and lipids in coronary artery disease

Gender and Lipids in Coronary Artery Disease

To the Editor.— The article by Reinhart et al 1 deserves special attention because of the inclusion of women (31%) into the study. Indeed, the authors found differences between men and women in the predictive power of certain lipoprotein and apolipoprotein (apo) measurements. In men, coronary artery disease was associated with elevated levels of apo B, total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol in serum and depressed apo A-I/B ratio. In women, coronary artery disease was associated with elevated apo B and triglyceride levels and depressed apo A-I/B ratio. These differences are worthy of note, because the expression of coronary artery disease in men is different from that in women and these differences are at least partially due to the sex-steroid milieu. 2 The contribution of menopause to the lipid profile may, in fact, be small, 3 but that of replacement sex hormones appears definite, albeit complex. 4

Monoclonal antibody EMR1a/212D recognizing site of deposition of extracellular lipid in atherosclerosis. Isolation and characterization of a cDNA clone for the antigen.

We have isolated from a rabbit liver cDNA library, clones coding for the 66-kDa glycoprotein (GP66) characterized previously by EMR1a/212D monoclonal antibody (Nakagami, K., Shimasaki, O., Sato, R., Komine, Y., Ohkuma, S. and Takano, T. (1989) Am. J. Pathol. 135, 93-100), which recognizes the extracellular regions of atherosclerotic arterial wall. The clone spans the sequence coding for the entire GP66 (456 amino acids) and 19 amino acids of signal peptide. GP66 deduced from nucleotide sequence contained an Arg-Gly-Asp cell attachment sequence and had a 76% amino acid sequence homology with human vitronectin. Furthermore, EMR1a/212D recognized rabbit vitronectin purified by heparin-affinity chromatography. RNA blot hybridization detected one transcript of the same size in normal and Watanabe-heritable hyperlipidemic rabbit liver. The levels of plasma GP66 and liver GP66 mRNA were not altered, whereas 9-fold greater accumulation of GP66 was observed in thoracic aorta of Watanabe-heritable hyperlipidemic rabbit. These results suggest that GP66 is rabbit vitronectin and that it is vitronectin which selectively accumulates in thoracic aorta with the development of atherosclerosis.

Platelet arachidonic acid metabolism in severe cerebrovascular disease

The ability of platelets to synthetise thromboxane B 2 and hydroxylated fatty acids from arachidonic acid was studied simultaneously with arachidonic acid-induced aggregation in 42 patients suffering from severe cerebral atherosclerosis and also in 34 healthy controls. Additionally, phospholipase-A 2-induced aggregation was performed as a probe for arachidonic acid located at the platelet surface. All the assays were performed with washed platelets, eliminating a possible influence of plasma. Platelets from patients were found responsive to significantly lower concentrations of arachidonic acid whereas thromboxane and hydroxylated fatty acid biosynthesis did not differ from controls. In the experimental conditions used, 75% of the control platelets underwent aggregation with phospholipase A 2 plus sphingomyelinase C, in comparison to only 50% for the patients, indicating the necessity for further analysis of the platelet membrane lipids in atherosclerosis.

Nature and significance of some plasma lipids in atherosclerosis

Thin layer chromatography analysis of serum lipids revealed a previously noted but unidentified spot that regularly occurs in atherosclerotic sera. Similar lipids are found also in thromboplastins, snake venoms, blood of some marsupials and, most copiously, in dead tissue. The main component of the spot has been proved to be a ceramide predominantly derived from C 16 -C 18 acids, presumably mostly hydroxy-acids. This ceramide also occurs in normal serum after stress, disappears after coagulation but can be re-extracted from the clot. Clotting and prothrombin times are significantly reduced by this lipid; such effects are counteracted by increased cholesterol. A second, minor component is probably a new kind of sphingolipid, possibly an analogue of cardiolipin.

Cytochemistry of lipids in atherosclerosis.

Cytochemistry of lipids in atherosclerosis.

The fatty acids of the serum in hypothyroidism.

SUMMARY The fatty acid patterns of the cholesterol ester, triglyceride and phospholipid fractions of serum from thirteen hypothyroid subjects have been determined using gas-liquid chromatography. A comparison was made with the results of similar analyses performed on sixteen apparently normal subjects and on eighteen patients with ischaemic heart disease. A trend towards increasing saturation was found in each of the fractions from the hypothyroid subjects. This was most marked in the cholesterol esters. The mechanism of the production of this trend is discussed and it is suggested that it is secondary to the hyperlipidaemia of hypothyroidism. Attention is drawn to the implication of these findings in interpreting the reported changes in the fatty acid composition of the serum lipids in atherosclerosis.

Serum triglycerides in coronary artery disease.

The identification of cholesterol as a constituent of atheromatous plaques has aroused recurrent waves of suspicion that lipid metabolism is in some way responsible for the development of atherosclerosis and coronary artery disease. Lipids are transported in serum as constituents of three major classes of compounds: cholesterol and its esters, phospholipids, and triglycerides or neutral fat. Most investigations in recent years have centered about the notion that serum cholesterol plays a causative role in the development of coronary artery disease in spite of numerous studies focusing attention on triglycerides. Included in these studies are reports of increased turbidity, increased and prolonged chylomicronemia, and increased ratio of β- to α-lipoproteins. Although triglycerides rather than cholesterol are chiefly responsible for turbidity of serum and constitute an important fraction of β-lipoproteins, the quantitative estimation of triglycerides has been largely neglected in studies of serum lipids in coronary artery disease. The present research was

THE INFLUENCE OF GONADAL HORMONES ON SERUM LIPIDS AND LIPOPROTEINS: STUDIES IN NORMAL AND HYPOGONADAL SUBJECTS

Excerpt Clinicians have known for almost 200 years that the manifestations of coronary atherosclerosis are much more frequent in men than in women. Numerous autopsy studies have disclosed the disea...

Effect of acute fat loads on serum lipids in atherosclerosis.

Since the imposition of a lipid load might uncover latent defects in lipid absorption or transport, "normal" individuals, and those with atherosclerosis, were subjected to test meals of butter fat, and qualitative and quantitative aspects of serum lipids and lipoproteins were measured. In contrast to the metabolic defects in diabetes mellitus which can be uncovered by a glucose load, the metabolic faults in atherosclerosis are not readily infuenced by single or repeated high fat meals.

Myocardial infarction in women.

Excerpt Even more striking than the relative rarity of coronary thrombosis in women in the reproductive phase of life is the fact that thrombosis is seldom due to spontaneous arteriosclerosis. The ...

The serum lipid pattern in hyperthyroidism, hypothyroidism and coron atherosclerosis

Serum lipids and serum lipoproteins were studied in twenty-five hyperthyroid and seventeen myxedema patients. Mean total lipid, total cholesterol and phospholipid levels were all significantly higher in the latter group. The beta lipoprotein and faster rising lipoprotein moieties showed a particularly striking increment, and contrasted with an insignificant difference in the alpha lipoproteins. The increase of the serum lipids in patients with hypothyroidism is qualitatively indistinguishable from that seen in idiopathic hypercholesterolemia which is so often associated with coronary atherosclerosis. However, when such hypercholesteremic patients are matched with hypothyroid patients as to sex, age and cholesterol level, a significantly higher beta lipoprotein fraction is found in the former group. This suggests that the hyperlipemia of atherosclerosis arises through a mechanism which is different from that of myxedema. This observation is also consistent with the idea that the primary abnormality of the serum lipids in atherosclerosis is an elevation in the level of beta lipoprotein.

The effect of estrogens on the plasma lipids in coronary artery disease

1. 1. Small doses of ethinyl estradiol depressed the plasma ester cholesterol in twenty hypercholesterolemic men with coronary artery disease. As the plasma phospholipids were uninfluenced, the plasma total-cholesterol: phospholipid ratio was also depressed. 2. 2. Some aspects of the role of the estrogenic hormones in lipid metabolism and atherosclerosis are discussed.