Levels of Prebeta-1 High-Density Lipoprotein Are a Strong Independent Positive Risk Factor for Coronary Heart Disease and Myocardial Infarction: A Meta-Analysis.

Background We previously showed that levels of prebeta-1 high-density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from cells, including artery wall macrophages, are positively associated with coronary heart disease (CHD) and myocardial infarction (MI) risk. Methods and Results In a multiethnic follow-up cohort of 1249 individuals from University of California-San Francisco clinics, we determined the degree to which prebeta-1 HDL levels, both absolute and percentage of apolipoprotein AI, are associated with CHD and history of MI. Independent, strong, positive associations were found. Meta-analysis revealed for the absolute prebeta-1 HDL for the top tertile versus the lowest, unadjusted odds ratios of 1.90 (95% CI, 1.40-2.58) for CHD and 1.79 (95% CI, 1.35-2.36) for MI. For CHD, adjusting for established risk factors, the top versus bottom tertiles, quintiles, and deciles yielded sizable odds ratios of 2.37 (95% CI, 1.74-3.25, P<0.001), 3.20 (95% CI, 2.07-4.94, P<0.001), and 4.00 (95% CI, 2.11-7.58, P<0.001), respectively. Men and women were analyzed separately in a combined data set of 2507 individuals. The odds ratios for CHD and MI risk were similar. Higher levels of prebeta-1 HDL were associated with all 5 metabolic syndrome features. Addition of prebeta-1 HDL to these 5 features resulted in significant improvements in risk-prediction models. Conclusions Analysis of 2507 subjects showed conclusively that levels of prebeta-1 HDL are strongly associated with a history of CHD or MI, independently of traditional risk factors. Addition of prebeta-1 HDL can significantly improve clinical assessment of risk of CHD and MI.

An approach to the proteomic analysis of a breast cancer cell line (SKBR-3).

This report describes the profiling of proteins in a sample prepared by laser capture microdissection (LCM) from a breast cancer cell line (SKBR-3). This experimental approach serves as a model system for proteomic studies on selected tissue samples and for studies of specific cell types. The captured cells were isolated in a dehydrated and reduced state and solubilized with a denaturing buffer. After dilution the protein mixture was digested with trypsin and the resulting peptide mixture was fractionated by reversed phase HPLC (RPLC) and analyzed on an ion trap mass spectrometer. A key part of this study is the combination of the LCM process with an extraction/digestion procedure that allowed effective solubilization of a significant part of the cellular sample in a single step. The identity of the peptides was determined by tandem mass spectrometry measurements in which the resulting spectra were compared with genomic and proteomic databases and protein identifications were made. While only peptides with a high probability assignment were used, the interpretation of mass spectral fragmentation patterns were also confirmed by manual interpretation of the spectra. Also, for the more abundant proteins the initial protein assignment from the best match peptide was strengthened by the observation of additional confirmatory peptide identifications. Another selection criteria was correlation of the mass spectrometric studies with clinical and genomic studies of potential cancer markers in tumor samples. This proteomic study allowed identification of the following proteins: human receptor protein kinase HER-2 or ERBB-2 and related kinases HER-3 and HER-4, the gene products from breast cancer type I and II susceptibility genes and cytoskeletal components such as cytokeratins 8, 18 and 19. Other proteins include fibroblast growth factor receptor variants (FGFR-2&4) and T-lymphoma invasion and metastasis inducing protein 1 (TIAM1). In addition several nonreceptor protein kinases YES, FAK and JAK-1 and 3 were identified. Since the study was performed on a limited number of cells (approximately 10,000) it raises the possibility of such studies being performed on individual patient samples prepared by needle biopsy.