phytosterols and Necrosis

The aim of this study was to evaluate the relationship between cholesterol metabolism and coronary plaque vulnerability.. Cholesterol homeostasis, defined as the balance between absorption and synthesis, influences the progression of coronary atherosclerosis.. Consecutive stable angina pectoris patients (N = 80) not receiving any lipid-lowering therapy were divided into 2 groups based on the presence of in vivo thin cap fibroatheroma (TCFA) in de novo target vessels assessed by the combined use of virtual histology intravascular ultrasound and optical coherence tomography.. Patients with in vivo TCFA (n = 42) showed a higher campesterol-to-lathosterol ratio (3.36 [interquartile range, 2.10 to 4.26] vs. 1.50 [1.20 to 2.50], p < 0.0001). The campesterol-to-lathosterol ratio, low-density lipoprotein (LDL) cholesterol, and high-sensitivity C-reactive protein (hsCRP) were positively correlated with the percentage of necrotic core volume (r = 0.520, p < 0.0001; r = 0.520, p < 0.0001; and r = 0.539, p < 0.0001, respectively) and negatively correlated with thinnest fibrous cap thickness (r = -0.566, p < 0.0001; r = -0.530, p < 0.0001; and r = -0.358, p = 0.007, respectively) . The independent predictors of the incidence of TCFA were the campesterol-to-lathosterol ratio (odds ratio: 3.989, 95% confidence interval: 1.688 to 9.428; p = 0.002), LDL cholesterol (odds ratio: 1.425, 95% confidence interval: 1.023 to 1.985; p = 0.03), hsCRP (odds ratio: 1.025, 95% confidence interval: 1.003 to 1.047; p = 0.02), and the percentage of necrotic core volume (odds ratio:1.084, 95% confidence interval: 1.012 to 1.161; p = 0.02).. Enhanced absorption and reduced synthesis of cholesterol may be related to coronary plaque vulnerability.

Topics: Aged; Angina, Stable; Biomarkers; C-Reactive Protein; Chi-Square Distribution; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Coronary Vessels; Disease Progression; Female; Fibrosis; Humans; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Necrosis; Odds Ratio; Phytosterols; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Risk Factors; Rupture, Spontaneous; Tomography, Optical Coherence; Ultrasonography, Interventional

Elicitins are family of small proteins secreted by species of the pathogenic fungus Phytophthora inducing a defence reaction in plants. They contain a hydrophobic cavity capable of binding sterols and fatty acids, and on the basis of their pI they are classified as either α-elicitins or more necrotising β-elicitins. The residue Lys13 was previously identified as a key determinant of the necrotising activity of basic elicitins. In the present study we describe changes in the ability of cryptogein, a β-elicitin inducing a hypersensitive response in tobacco, to transfer sterols and fatty acids between micelles and liposomes upon Lys13Val mutation. We propose that the change in activity is influenced by the elimination of positive charge on the surface of cryptogein, which is significant for correct positioning of the protein during lipid loading, without adversely affecting the binding of sterol to the cavity of the protein. Compared to wild type cryptogein, mutation Lys13Val resulted in lowered expression of defence-related genes and compromised resistance to Phytophthora parasitica. Furthermore, resistance induced by Lys13Val mutant was similar to that induced by acidic elicitin capsicein containing at amino position 13 valine Determined results sustained a crucial role of positive lysine residues on the surface of basic elicitins and suggested their significant role in correct protein-membrane interaction and thus on their biological activity.

Topics: Algal Proteins; Biological Transport; Electricity; Fatty Acids; Fungal Proteins; Gene Expression; Genes, Plant; Host-Pathogen Interactions; Lipid Metabolism; Liposomes; Lysine; Micelles; Mutation; Necrosis; Oomycetes; Phytosterols; Plant Diseases; Plant Immunity; Valine

Proportions of cholesterol precursors (squalene, delta 8-cholestenol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol) and cholestanol to cholesterol in serum were measured before and serially after liver transplantation in eight patients with primary biliary cirrhosis (PBC) and three with acute liver necrosis. The preoperative proportions of cholestanol were 12 and 3-times higher in the PBC and necrosis groups, respectively, than in a control group of 27 individuals, while those of lathosterol were low in both groups and the campesterol/sitosterol ratio in the PBC group. During the operation the proportions of cholestanol fell sharply and those of lathosterol rose especially in the PBC group. During the postoperative follow-up of 5 weeks the proportions of the non-cholesterol sterols were markedly improved especially in the necrosis group yet those of cholestanol remained high and the campesterol/sitosterol ratios low, particularly in the PBC group. The proportions of lathosterol increased gradually almost to the control limits within the postoperative 5-week period, whereas those of desmosterol decreased. The non-cholesterol sterol values were not related to acute rejections, while significant correlations of cholestanol to liver function tests was found especially at the end of the follow-up.

Topics: Acute Disease; Adult; Cholestanol; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Liver Diseases; Liver Transplantation; Male; Middle Aged; Necrosis; Phytosterols; Protein Precursors; Sitosterols; Squalene