Variations in inflammatory markers in acute myocardial infarction: a longitudinal study.

Inflammation is now considered a key component of atherosclerosis, from fatty streak formation to plaque rupture, subsequent thrombosis, and progressive mechanical and dynamic obstruction. Rupture of the arterial plaque's fibrous cap exposes tissue factors present in the necrotic core, triggering inflammatory signaling, cell adhesion, and the coagulation cascade that eventually leads to thrombus. Cytokines and adhesion molecules are key components of these events that contribute to the development of an atherosclerotic plaque. The cytokine TNF-alpha and intercellular adhesion molecule-1 (ICAM-1) are indicators of basal inflammation, while the soluble forms of adhesion molecules such as CD40L and P-selectin indicate the extent of platelet activation. This study reports on the follow-up of 17 patients with confirmed acute myocardial infarction (AMI group) undergoing angioplasty and a matched control group of 16 patients without coronary artery disease as verified by coronary angiography. Patients from the AMI group were assessed at the onset of the acute coronary syndrome, within 24 h, before the administration of glycoprotein IIb/IIIa inhibitors and coronary angioplasty, and during the recovery period, two and 40 days after intervention. For both groups, clinical characteristics were documented and serum concentrations of soluble CD40L, P-selectin, ICAM-1, TNF-alpha, and conventional biochemical indicators were analyzed. For AMI patients, these indicators were recorded at study entry and during follow-up. Concentrations of cytokines and adhesion molecules were measured using commercial immunoassay (ELISA) kits. Significant variations in sP-selectin were observed relative to the control group. Immediately after myocardial infarction, sP-selectin levels rose markedly, followed by a sharp decrease two days later. After 40 days of recovery, sP-selectin levels rose again, returning to the initial values. Variations in sCD40L levels were not significant relative to controls. However, sCD40L concentrations tended to fall until the second day after infarction, followed by a rise, and by the 40th day of recovery levels were slightly higher than controls. Unlike sCD40L and sP-selectin, consistently higher levels of TNF-alpha relative to controls were observed, which were only significant after 40 days of recovery. No significant variations were observed for ICAM-1 serum concentrations in the AMI group. The variations observed demonstrate the role of inflammatory markers in AMI progression and highlight the importance of systemic inflammation in disease evolution. The increased concentration of sP-selectin at infarction onset is evidence of thrombosis and platelet activation. Later, during the recovery period when hemodynamic variables are returning to stability in part due to medication, rises in circulating levels of sCD40L and cytokines such as TNF-alpha may reflect the role of these molecules in the recovery of endothelial and myocardial tissues.

Systemic markers of the redox balance and apolipoprotein E polymorphism in atherosclerosis: the relevance for an integrated study.

Prospective studies have demonstrated that an imbalance between oxidative damage and antioxidative protection can play a role in the development and progression of atherosclerosis. Also, genotypes with the apolipoprotein E epsilon4 allele have been associated with an increase risk for this pathology. Based on this knowledge, the aim of this study was to evaluate indicators of the redox balance, trace elements, and apolipoprotein E allelic profile in subjects from the Lisbon population with clinically stable atherosclerosis, at risk for atherosclerotic events, and in healthy subjects for comparison. The activities of superoxide dismutase in erythrocytes and glutathione peroxidase in whole blood, plasma total thiols, and serum ceruloplasmin were kept unchanged among the three groups. Serum alpha- tocopherol was increased in atherosclerotic patients. Total malondialdehyde in serum and protein carbonyls in plasma, which are indicators of lipid and protein oxidative damage, respectively, reached their highest values in risk subjects. The concentrations of potassium and calcium, in plasma and in blood cells, were slightly elevated in patients and might reflect an electrolytic imbalance. Regarding the apolipoprotein E polymorphism, atherosclerotic patients had an increased incidence of the high-risk genotypes for atherogenesis (epsilon3/epsilon4 and epsilon4/epsilon4). A multivariate model applied to the general population using most of the parameters clearly separated the three groups at study (i.e., the healthy group from the steady-state group of risk disease and from the atherosclerotic one). As shown by us, the usefulness of biochemical and complementary genetic markers is warranted for a better knowledge on atherosclerosis molecular basis.

Cholesterol-lowering effects of dietary blue lupin (Lupinus angustifolius L.) in intact and ileorectal anastomosed pigs.

The present study was undertaken to investigate the effect of cholesterol-enriched casein (CAS) and blue lupin seed (BL) diets on the cholesterol metabolism of intact (INT) and ileorectal anastomosed (IRA) pigs. For 3 weeks, four groups of six pigs were allocated to the treatments (CAS-INT, CAS-IRA, BL-INT, and BL-IRA). Diet-induced hypercholesterolemia was inhibited by the BL through a substantial decrease in plasma LDL-cholesterol. The BL also reduced liver esterified and total cholesterol, increased hepatic LDL receptor synthesis and HMG-CoA reductase activity, and stimulated intestinal bile acid reabsorption. The neutral sterol output was higher in BL- than in CAS-fed pigs. The bile acid output was lower in IRA than in INT pigs. Surgery also prevented steroid microbial transformation, but it did not influence plasma cholesterol levels. These results suggest that the hypocholesterolemic effect of the BL, compared with the CAS, is attributable to impaired intestinal cholesterol absorption, probably involving increased bile acid reabsorption and higher contents of dietary phytosterols, both factors that reduce the micellar solubilization of cholesterol. Furthermore, according to our data, the contribution of the large intestine to cholesterol metabolism is very weak.

Dietary raw peas (Pisum sativum L.) reduce plasma total and LDL cholesterol and hepatic esterified cholesterol in intact and ileorectal anastomosed pigs fed cholesterol-rich diets.

Previous studies demonstrated the cholesterol-lowering effect of dietary legumes (mainly soybeans) in animals and humans, but the mechanisms by which they exert this effect are not completely understood. The contribution of the hindgut to this hypocholesterolemic effect is also not well documented. The present work was undertaken to investigate the effect of cholesterol-enriched (2.8 g/kg) casein (C) and raw pea seed (RP) diets on the cholesterol metabolism of intact (I) and ileorectal anastomosed (IRA) growing pigs. Four groups of 6 pigs were allocated to the treatments (C-I, C-IRA, RP-I, and RP-IRA pigs) for 3 wk. Plasma total cholesterol was lowered by the RP diet through a significant decrease in LDL cholesterol. The RP diet also decreased the hepatic concentration of esterified cholesterol and increased 3-hydroxy-3-methylglutaryl CoA reductase activity and LDL receptor synthesis. The biliary total cholesterol and bile acid concentrations were greater in RP- than in C-fed pigs. In addition, fecal bile acid output was higher in RP-fed pigs. The cecum-colon by-pass inhibited cholesterol and beta-sitosterol microbial transformation, lowered the bile acid output, and increased the primary to secondary bile acid output ratio, but its influence on cholesterolemia was negligible. These results suggest a hypocholesterolemic effect of the raw pea diet probably due to increased fecal bile acid output and an increased biliary bile acid concentration.

Effect of cigarette smoking on serum alpha-tocopherol and the lipid profile in a Portuguese population.

BACKGROUND: The present study was conducted to determine the effects of cigarette smoking on the levels of serum alpha-tocopherol and on the lipid profile in humans from the Lisbon population. METHODS: Serum alpha-tocopherol was evaluated by a reverse-phase HPLC method with UV detection. Enzymatic tests were used for the evaluation of the lipid profile. RESULTS: Smokers in general and female smokers in particular had decreased alpha-tocopherol levels when compared with nonsmokers. Smokers had also lower HDL cholesterol (HDL-C) contents, but this difference was statistically significant only for females. Regardless of sex, in smokers, there was a positive correlation between alpha-tocopherol and triglyceride (TG) levels. Cluster analysis showed a sex-independent separation between smokers and nonsmokers. CONCLUSION: These results suggest a different interaction of these blood parameters in smokers versus nonsmokers that should be further investigated.

Effects of ileo-rectal anastomosis on cholesterol metabolism in pigs fed either casein or extruded soya beans.

The importance of legume proteins in cholesterol metabolism has been recognised, but the hindgut contribution is still unclear. The present work was undertaken to address the role of the caecum-colon in cholesterol metabolism in intact (I) and ileo-rectal anastomosed (IRA) pigs fed with casein or extruded soyabean (ES) diets. Four groups of six growing pigs were assigned to the treatments (casein-I, casein-IRA, ES-I, ES-IRA) for 3 weeks. Plasma total cholesterol, LDL- and HDL-cholesterol were not modified by surgery or diet. In the liver, the ES diet significantly depressed non-esterified, esterified and total cholesterol. The treatments did not affect hepatic 3-hydroxy-3-methylglutaryl CoA reductase, cholesterol 7alpha-hydroxylase or sterol 27-hydroxylase activities. In the gallbladder bile of ES-fed pigs, total cholesterol was depressed while total bile acid concentration was increased. IRA and the ES diet markedly decreased the biliary bile acid microbial metabolites (namely hyodeoxycholic acid) and increased the primary bile acids (mainly hyocholic acid). The concentration of bile hydrophobic acids was decreased only by the ES diet. Faecal neutral sterol output was increased in ES-fed pigs, but the bile acid and the sum of neutral and acidic steroid outputs were not. Microbial transformation of neutral and acidic steroids was markedly reduced by IRA, especially in the ES-fed pigs. Thus, surgery and ES modulated the steroid profile but the caecum-colon did not seem to play a crucial role in determining cholesterolaemia in pigs.