PROTEOMIC AND GENOMIC ANALYSIS OF CARDIOVASCULAR DISEASE
SECTION GENOMICS LARGE SCALE EXPRESSION PROFILING IN CARDIOVASCULAR DISEASE USING MICROARRAYS: PROSPECTS AND PITFALLS DNA MICROARRAY TECHNOLOGIES CDNA MICROARRAYS OR OLIGONUCLEOTIDE ARRAYS? DESIGNING MEANINGFUL EXPERIMENTS COMPUTATIONAL ANALYSIS OF MICROARRAY DATA RAW DATA ANALYSIS COMPARING EXPRESSION DATA CLUSTERING ALGORITHMS DATA SHARING POTENTIAL USE OF THIS TECHNOLOGY IN UNDERSTANDING COMPLEX HEART DISEASE ACKNOWLEDGEMENTS REFERENCES GLOBAL GENOMIC ANALYSES OF CARDIOVASCULAR DISEASE: A POTENTIAL MAP OR BLIND ALLEY? BLINDLY SEARCHING FOR STRUCTURE-FUNCTION THE STARTING LINE: GARBAGE IN – GARBAGE OUT? IS THE MOUSE A VALID MODEL FOR HUMAN-BASED DISEASE TRANSCRIPTOME STUDIESE? ARRAYS AND CARDIOVASCULAR DISEASE FILTERING THE TRANSCRIPTOME: ENHANCING THE VALUE CONCLUDING REMARKS CONTENTS HEART FAILURE: A GENOMICS APPROACH OVERVIEW OF HEART FAILURE PATHOPHYSIOLOGY OF HEART FAILURE GENOMIC APPROACH TO HEART FAILURE CONCLUSION PRINCIPLES OF CDNA MICROARRAYS AS APPLIED IN HEART FAILURE RESEARCH THE CLINICAL PROBLEM THE NEED FOR A NEW PARADIGM THE POTENTIAL ROLE OF THE MICROARRAY STRENGTHS OF MICROARRAY TECHNOLOGY CAVEATS OF USING THE MICROARRAY TECHNOLOGY EXPERIMENTAL DESIGN TISSUE PREPARATION AND PRESERVATION RNA ISOLATION RNA AMPLIFICATION PROBE LABELING DATA ANALYSIS AND BIOINFORMATICS APPLICATION: NEW CLASSIFICATION OF DISEASE APPLICATION: PATHOGENESIS OF DISEASE APPLICATION: EARLY DISEASE MARKERS AND PROGNOSIS APPLICATION: THERAPEUTIC INSIGHTS GENE PROFILING IN THE HEART BY SUBTRACTIVE HYBRIDIZATION STRATEGIES AND LIMITATIONS OF GENOME PROFILING THE BIOLOGICAL PROBLEM THE MODEL THE TECHNOLOGICAL APPROACH ANALYZING GENE EXPRESSION BY SUBTRACTIVE HYBRIDIZATION METHODOLOGY ADVANTAGES AND DISADVANTAGES GENOMICS OF MYOCARDIAL ISCHEMIA SUBTRACTIVE HYBRIDIZATION OF MYOCARDIAL ISCHEMIA MYOCARDIAL STUNNING GENOMIC PROFILE OF MYOCARDIAL STUNNING CHASING NOVEL GENES SUMMARY DNA MICROARRAY GENE PROFILING: A TOOL FOR THE ELUCIDATION OF CARDIOPROTECTIVE GENES INTRODUCTION CANDIDATES FOR CARDIOPROTECTIVE GENES AND POSSIBLE MECHANISM(S) OF PROTECTION CANDIDATE GENES INVOLVED IN CARDIOPROTECTION POTENTIAL MECHANISMS OF CARDIOPROTECTION IS THERE A COMMON SET OF CARDIOPROTECTIVE GENES? EFFECTS OF LONG-TERM ACTIVATION AND DOSAGE OF CARDIOPROTECTIVE GENES APPROACHES TO IDENTIFY GENES INVOLVED IN CARDIOPROTECTION PRECONDITIONING TRANSGENIC MODELS OF PROTECTION CARDIOPROTECTION IN FEMALES HUMAN STUDIES PRACTICAL CONSIDERATIONS IN MICROARRAY TECHNOLOGY SAMPLE SELECTION VARIABILITY IN HYBRIDIZATION CROSS-HYBRIDIZATION OF SEQUENCES IMPORTANCE OF REPLICATE HYBRIDIZATIONS AND VALIDATION OF SIGNIFICANTLY CHANGED GENES CHANGES IN GENE EXPRESSION VERSUS PROTEIN OR ACTIVITY BIOINFORMATICS OR HOW TO TELL THE FOREST FROM THE TREES PITFALLS ASSOCIATED WITH CDNA MICROARRAYS – A CAUTIONARY TALE PHASE 1: THE ORIGINAL EXPERIMENTAL DESIGN PHASE 2: VALIDATION AND TROUBLESHOOTING PHASE 3: “POSTMORTEM” ANALYSIS AT RESGEN PHASE 4: FUTURE DIRECTIOINS CAVEAT EMPTOR: SUGGESTIONS FOR NEW ARRAY USERS FINAL THOUGHTS APPLICATION OF BIOLOGIC SKEPTICISM TO ANALYSIS OF EXPRESSION PHENOTYPES WHAT IS AN ARRAY? APPLICATIONS OF ARRAY ANALYSIS CATALOGS BY FUNCTION FUNCTIONAL GENOMICS PHENOTYPIC DEFINITIONS METHODOLOGICAL BIASES IN ARRAY INTERPRETATION USEFULNESS OF CLUSTERED GENES FALSE ASSOCIATIONS HYPOTHESES BASED ON EXPRESSION PHENOTYPES MULTIPLE VENN DIAGRAMS: DECREASING THE SIZE OF THE CATALOG ANALYSIS OF MEASUREMENT ERRORS STANDARDS AND STATISTICAL VALIDATION GENES INVOLVED IN ATHEROSCLEROSIS AND PLAQUE FORMATION GENES INFLUENCING ATHEROGENESIS DNA ARRAYS: THE PRINCIPLE DNA ARRAYS IN THE RESEARCH OF ATHEROSCLEROSIS PROTEOMICS GENE EXPRESSION PROFILING IN PULMONARY AND SYSTEMIC VASCULAR CELLS EXPOSED TO BIOMECHANICAL STIMULI PRINCIPLES OF ARRAY, SAGE AND MINI SAGE TECHNOLOGIES ANALYSIS OF GENE EXPRESSION PROFILING IN VASCULAR CELLS ENDOTHELIAL CELLS SMOOTH MUSCLE CELLS FIBROBLASTS MONOCYTES/MACROPHAGES FUTURE PERSPECTIVES PROTEOMICS, A STEP BEYOND GENOMICS: APPLICATIONS TO CARDIOVASCULAR DISEASE PROTEIN SOLUBILIZATION PROTEIN SEPARATION PROTEIN DETECTION/VISUALISATION PROTEIN IDENTIFICATION BIOINFORMATICS CARDIOVASCULAR PROTEOMICS HEART 2DE PROTEIN DATABASES DILATED CARDIOMYOPATHY ANIMAL MODELS OF HEART DISEASE PROTEOMIC CHARACTERIZATION OF CARDIAC ANTIGENS IN HEART DISEASE AND TRANSPLANTATION MASS SPECTROMETRY – A POWERFUL ANALYTICAL TOOL IONISATION PROCESSES MASS ANALYSERS STRATEGIES FOR PROTEIN AND CHARACTERISATION PROTEIN IDENTIFICATION BY MALDI-TOF PROTEIN IDENTIFICATION BY TANDEM MX/MS DATABASE SEARCHING POST TRANSLATIONAL MODIFICATIONS DIFFERENTIAL EXPRESSION PROTEOMIC ANALYSIS USING ISOTOPE CODED AFFINITY TAGS TRADITIONAL METHODOLOGIES FOR MEASURING PROTEIN ABUNDANCE ISOTOPIC METHODOLOGIES TO QUANTITATIVE PROTEOMICS ISOTOPE-CODED AFFINITY TAGS (ICATTM) FOR QUANTITATIVE PROTEOME ANALYSIS BIOLOGICAL APPLICATIONS OF THE ICAT METHOD CONCLUSIONS AND FUTURE DIRECTIONS PROTEIN CHIP TECHNOLOGY IN PROTEOMICS ANALYSIS TWO-DIMENSIONAL GEL ELECTROPHORESIS ALTERNATIVE APPROACHES TO PROTEIN SEPARATION PROTEIN ARRAYS PROTEIN RECOGNITION MOLECULES IMMOBILISATION OF PRMS ARRAYING OF PROTEINACEOUS PRMS ARRAYING OF NUCLEIC ACID PRMS ARRAYING OF SYNTHETIC PRMS DETECTION METHODS CONCLUSIONS RECENT APPLICATIONS OF FUNCTIONAL PROTEOMICS: INVESTIGATIONS IN SMOOTH MUSCLE CELL PHYSIOLOGY INTRODUCTION TO FUNCTIONAL PROTEOMICS EXPRESSION PROTEOMICS (CATALOGUE) FUNCTIONAL PROTEOMICS (APPLIED) STRUCTURAL PROTEOMICS PROTEOMIC TOOLS FOR SMOOTH MUSCLE PHYSIOLOGISTS PROTEIN SEPARATION: THE 2DE TECHNOLOGY MASS SPECTROMETERS PROTEIN IDENTIFICATION BY DATABASE SEARCHING DEFINING SIGNAL TRANSDUCTION MODULES IN SMOOTH MUSCLE PROTEOME MINING OF THE SMOOTH MUSCLE CELL IDENTIFICATION OF TARGETS OF PHOSPHORYLATION IN HEART MITOCHONDRIA EXPERIMENTAL APPROACH AND PITFALLS PERSPECTIVE AND COMMENTS ANALYSIS OF POST-TRANSLATIONAL MODIFICATIONS DETECTION OF PHOSPHOPROTEINS BY COMPARISON OF TWO CONDITIONS CAN BE A TOOL TO SELECT PROTEINS OF POTENTIAL INTEREST FOR PROTEOMIC ANALYSIS SELECTION OF AN ORGANELLE SIMPLIFIES THE ANALYSIS FURTHER SIMPLIFICATION OF THE MIXTURE OF PROTEINS TO BE ANALYZED IS DESIRABLE SELECTION OF A PROTEIN SEPARATION STRATEGY IS ESSENTIAL SPECIFIC METHODS EMPLOYED ISOLATED PERFUSED HEART ISOLATION OF CYTOSOL AND MITOCHONDRIA IN VITRO PHOSPHORYLATION REACTIONS SUBMITOCHONDRIAL FRACTIONATION PREPARATION OF SAMPLES FOR 2D PAGE AND MS MALDI ANALYSIS PEPTIDE SEQUENCING BY MS/MS ANALYSIS PROTEOMIC CHARACTERIZATION OF PROTEIN KINASE C SIGNALING TASKS IN THE HEART PROTEIN KINASE C SIGNALING COMPLEXES METABOLISM-TARGETED PROTEOMICS TRANSCRIPTION-TARGETED PROTEOMICS SUBPROTEOMIC ANALYSIS OF PKC SIGNALING FUNCTIONAL PROTEOMIC PLATFORM METABOLIC AND TRANSCRIPTION/TRANSLATION FUNCTIONS OF THE PKC COMPLEX IDENTIFICATION OF SECRETED OXIDATIVE STRESS-INDUCED FACTORS (SOXF) AND ASSOCIATED PROTEINS: PROTEOMICS IN VASCULAR BIOLOGY IDENTIFICATION OF SOXF BY TANDEM MS SECRETED FACTORS ARE INVOLVED IN REGULATION OF ERK1/2 ACTIVATION BY OXIDATIVE STRESS PURIFICATION OF SOXF AND IDENTIFICATION OF SOXF CANDIDATE PROTEINS BY MASS SPECTROMETRY LY83583 STIMULATES RELEASE OF HSP90- SPECIFICALLY FROM VSMC HUMAN RECOMBINANT CYCLOPHILIN A STIMULATES VSMC GROWTH AND PROTECTS VSMC AGAINST APOPTOSIS IDENTIFICATION OF SOXF-ASSOCIATED PROTEINS BY MALDI-TOF MS CONFIRMATION OF 43-KD CYPA-BINDING PROTEIN AS A -ACTIN MYOFILAMENT PROTEOMICS: UNDERSTANDING CONTRACTILE DYSFUNCTION IN CARDIORESPIRATORY DISEASE REGULATION OF MUSCLE CONTRACTION DISEASE STATES AND THE MYOFILAMENT PROTEINS MYOFILAMENT PROTEIN MUTATIONS CAUSE DISEASE MYOFILAMENT PROTEIN ISOFORM ALTERATIONS IN DISEASE MYOFILAMENT PROTEIN POST-TRANSLATIONAL MODIFICATIONS IN DISEASE PROTEOMIC ANALYSIS OF THE MYOFILAMENT PROTEINS CREATING A MYOFILAMENT PROTEOME PROTEIN SEPARATION – 2-DE DETECTION, QUANTIFICATION AND IDENTIFICATION ALTERNATIVE METHODS OF PROTEIN SEPARATION THE NEXT STEP – CLINICAL APPLICATIONS OF PROTEOMICS: THE DEVELOPMENT OF BIOMARKERS GENOMICS PERSPECTIVE FOR DRUG DISCOVERY HUMAN GENOME GENOMICS AND THE PROCESS OF DRUG DISCOVERY GENOMICS AND TARGET IDENTIFICATION GENOMICS AND TARGET VALIDATION GENOMICS AND LEAD IDENTIFICATION AND REFINEMENT GENOMICS AND LEAD VALIDATION GENOMICS AND INDIVIDUALIZATION OF DRUG THERAPY PROTEOMICS: A POST-GENOMIC PLATFORM FOR DRUG DISCOVERY AND DEVELOPMENT PERSPECTIVES ON THE DRUG DISCOVERY AND DEVELOPMENT PROCESS EMERGING PROTEOMIC TECHNOLOGIES IN R & D TARGET IDENTIFICATION CARDIOVASCULAR DISEASES CANCER INFECTIOUS DISEASES INFLAMMATION AND IMMUNE FUNCTION TARGET/DRUG VALIDATION TOXICOPROTEOMICS BIOMARKER DISCOVERY NEUROLOGICAL DISEASES INFLAMMATORY DISEASES MISCELLANEOUS DISEASES THE CHANGING PHARMACEUTICAL R & D LANDSCAPE