ABSTRACT
Cystatin C (CysC), an endogenous inhibitor of cysteine proteases and a sensitive and accurate marker of renal function, is associated with the severity of coronary atherosclerosis assessed by angiography and future cardiovascular events according to previous studies. We aimed to evaluate the association between CysC levels and coronary plaque volume, composition and phenotype assessed by intravascular ultrasound and intravascular ultrasound-derived virtual histology in patients with preserved renal function. Forty-four patients with angiographically documented coronary artery disease and complete intravascular imaging were included in the study. Patients were categorized into tertiles by CysC levels. Subjects in the high CysC tertile had significantly higher mean plaque burden (48.0 % ± 6.9 vs. 42.8 % ± 7.4, P = 0.029), lower mean lumen area (8.1 mm2 ± 1.7 vs. 9.9 mm2 ± 3.1, P = 0.044) and a higher number of 5-mm vessel segments with minimum lumen area < 4 mm2 (17.9 ± 18.9 vs. 6.8 ± 11.7, P = 0.021) compared to patients in the lower tertiles. In addition, CysC levels demonstrated significant positive correlation with the mean plaque burden (r = 0.35, P = 0.021). Neither relative, nor absolute plaque components differed significantly according to CysC tertiles. The Liverpool Active Plaque Score was significantly higher in the high CysC tertile patients (0.91 ± 1.0 vs. 0.18 ± 0.92, P = 0.02). In conclusion, our study demonstrated a significant association of increased CysC levels with more advanced coronary artery disease and higher risk plaque phenotype in patients with preserved renal function.
Subject(s)
Coronary Artery Disease/metabolism , Coronary Artery Disease/physiopathology , Cystatin C/metabolism , Kidney Function Tests , Kidney/metabolism , Kidney/physiopathology , Biomarkers/metabolism , Female , Glomerular Filtration Rate , Humans , Inflammation/pathology , Male , Middle Aged , Phenotype , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/physiopathology , Tumor Necrosis Factor-alpha/metabolism , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
Immunohistochemical studies of the presence of lactosylceramide (LacCer) in lysosomal storage disorders (LSDs) were done using anti-LacCer monoclonal antibody of the CDw 17 type (clone MG-2). No sign of an association between LacCer and the lysosomal system in normal cells was observed, except for histiocytes active in phagocytosis. A comparative study of a group of LSDs showed a general tendency for LacCer to increase in storage cells in Niemann-Pick disease type C (NPC), and types A and B, GM1 gangliosidosis, acid lipase deficiency, glycogen storage disease type II and mucopolysaccharidoses. LacCer accumulated in storage cells despite normal activity of relevant lysosomal degrading enzymes. The accumulation of LacCer displayed variability within storage cell populations, and was mostly expressed in neurons in NPC. An absence of the increase in LacCer in storage cells above control levels was seen in neuronal ceroid lipofuscinoses (neurons and cardiocytes) and in Fabry disease. Gaucher and Krabbe cells showed significantly lower levels, or even the absence, of LacCer compared with control macrophages. Results of immunohistochemistry were corroborated by semiquantitative lipid thin-layer chromatography (TLC). It is suggested that different associations of LacCer with the lysosomal storage process may reflect differences in glycosphingolipid turnover induced by the storage-compromised lysosomal/endosomal system.
