Endothelial Dysfunction and Inflammation (Progress in Inflammation Research)

Endothelial Dysfunction and Inflammation (Progress in Inflammation Research)......Page 1
Front-matter......Page 2
Endothelial Dysfunction and Inflammation......Page 4
Copyright......Page 5
Contents......Page 6
List of contributors......Page 8
Preface......Page 12
The sepsis continuum......Page 14
Activation and dysfunction......Page 15
Acknowledgements......Page 0
Hemostasis......Page 16
Permeability......Page 18
Leukocyte adhesion......Page 19
Apoptosis......Page 20
Conclusion......Page 21
References......Page 22
Introduction......Page 27
Endothelial engagement in inflammation......Page 28
Microvascular endothelial heterogeneity in normal conditions......Page 31
Endothelial origin affects response to an inflammatory stimulus......Page 34
In vivo microvascular heterogeneity in reaction to inflammatory stress......Page 36
Studying the molecular basis of endothelial heterogeneity – Some technological considerations......Page 39
Concluding remarks......Page 40
References......Page 41
Abstract......Page 48
Reactive oxygen species......Page 49
Reactive nitrogen species......Page 51
Elevated ROS production in vascular disease leads to the formation of powerful oxidising species......Page 53
ROS-mediated damage to cellular macromolecules......Page 54
Impaired NO signalling......Page 56
Activation of pro-inflammatory signalling cascades......Page 57
NADPH oxidases are primary sources of ROS in the vessel wall......Page 58
Xanthine oxidoreductase......Page 65
Mitochondrial respiratory chain......Page 66
Conclusion......Page 68
References......Page 69
Abstract......Page 76
Influence of cellular localization on eNOS activity......Page 77
Modulation of eNOS activity by regulatory proteins......Page 78
Protein-protein interactions in inflammation......Page 80
Regulation of eNOS activity by phosphorylation......Page 81
Phosphorylation of eNOS in inflammation......Page 83
Conclusion......Page 84
References......Page 85
Pulmonary arterial hypertension......Page 92
Endothelium and endothelial dysfunction in PAH......Page 93
Nitric oxide......Page 94
Prostacyclin......Page 95
Thromboxane A2......Page 96
Current PAH therapies and endothelial dysfunction......Page 97
Endothelial dysfunction and inflammation in PAH......Page 99
EC apoptosis and the genetics of PAH......Page 100
Bone morphogenetic protein receptor 2 mutations......Page 101
Mutations in Alk-1 and other members of the TGF-β superfamily......Page 102
Ang1-Tie2 pathway......Page 103
Mechanistic link between EC apoptosis and PAH......Page 104
References......Page 106
General considerations......Page 114
Blood pressure regulation and endothelial dysfunction......Page 115
NO bioavailability and inactivation......Page 116
Prostacyclin......Page 117
ED vs hypertension: Which comes first? A mechanistic evaluation......Page 118
Hitting two birds with one stone: Improving endothelial function and blood pressure control......Page 119
Tetrahydrobiopterin (BH4) supplementation......Page 121
Conclusion......Page 122
Sphingosine-1-phosphate: Sources, metabolism and carriers......Page 129
S1P and its receptors......Page 130
S1P in endothelial cell migration, angiogenesis and morphogenesis......Page 131
S1P and the maintenance of the endothelial barrier......Page 133
S1P and adhesion of inflammatory cells to activated endothelium......Page 134
Interplay of S1P with HDL as its major carrier, buffer and distributor......Page 136
S1P agonists and antagonists as possible therapeutics in endothelial inflammation......Page 137
References......Page 138
Introduction......Page 146
Components in TNFR1 signaling......Page 147
Divergence of TNF-TNFR1-mediated NF-kB and JNK signaling pathways......Page 149
Endocytosis and TNF-R1 signaling......Page 150
ASK1 activation by TNF......Page 151
ASK1 activation by oxidative stress......Page 153
Anti-inflammation strategies......Page 154
Inhibiting ASK1-JNK signaling may be a better anti-inflammatory strategy......Page 155
Role of TNF-R2 in inflammation......Page 156
Function of TNFR2 signaling in inflammatory angiogenesis......Page 158
Acknowledgements......Page 159
References......Page 160
Endothelial dysfunction in diabetes and advanced glycation end products......Page 169
AGE binding proteins......Page 170
Vascular AGE-RAGE signalling......Page 172
Diabetes-associated atherosclerosis and RAGE blockade......Page 173
Conclusion......Page 174
References......Page 175
Introduction......Page 183
Endothelial cell phenotype in arterial regions predisposed to atherosclerosis......Page 185
Abundance of resident intimal DC correlates with regional and genetic susceptibility to atherosclerosis......Page 186
Cellular and molecular mechanisms underlying the accumulation of RIDC in the atherosclerosis-prone areas of the aorta......Page 187
Potential functions of RIDC in the normal aorta......Page 189
RIDC participate in the initiation of atherosclerosis......Page 190
Significance......Page 191
References......Page 192
Introduction......Page 197
Nitric oxide......Page 198
Endothelium-dependent hyperpolarizations......Page 200
Endothelium-depending contracting factors......Page 201
Oxidative stress and inflammation in aged animals......Page 202
Regenerated endothelium......Page 203
References......Page 204
Introduction......Page 209
Invasive assessment of endothelial function......Page 210
Clinical evaluation of FMD......Page 211
Assessment of diameter change......Page 213
Assessment of flow......Page 214
Assessment of endothelium-independent vasodilatation......Page 216
Pulse wave velocity......Page 217
Peripheral waveform analysis......Page 218
Practical application of endothelial function testing for assessment of the vascular effects of inflammation......Page 219
References......Page 221
Microcirculatory failure mediates organ dysfunction in inflammatory disorders such as sepsis......Page 226
Measures of success in reversing endothelial dysfunction......Page 227
Specific therapies......Page 229
Therapies targeting inflammatory cytokines and their receptors......Page 230
Modulation of the coagulation-inflammatory pathway......Page 231
Therapies targeting intracellular inflammatory signaling......Page 232
Future directions in the treatment of endothelial dysfunction......Page 233
References......Page 234
Index......Page 238