title: The role of intrinsic apoptotic signaling in hemorrhagic shock-induced microvascular endothelial cell barrier dysfunction.
abstract: Hemorrhagic shock leads to endothelial cell barrier dysfunction resulting in microvascular hyperpermeability. Hemorrhagic shock-induced microvascular hyperpermeability is associated with worse clinical outcomes in patients with traumatic injuries. The results from our laboratory have illustrated a possible pathophysiological mechanism showing involvement of mitochondria-mediated "intrinsic" apoptotic signaling in regulating hemorrhagic shock-induced microvascular hyperpermeability. Hemorrhagic shock results in overexpression of Bcl-2 family of pro-apoptotic protein, BAK, in the microvascular endothelial cells. The increase in BAK initiates "intrinsic" apoptotic signaling cascade with the release of mitochondrial cytochrome c in the cytoplasm and activation of downstream effector caspase-3, leading to loss of endothelial cell barrier integrity. Thus, this review article offers a brief overview of important findings from our past and present research work along with new leads for future research. The summary of our research work will provide information leading to different avenues in developing novel strategies against microvascular hyperpermeability following hemorrhagic shock.
authors.affiliation: Department of Surgery, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA, 30310, USA.
authors.forename: Devendra A
authors.initials: DA
authors.lastname: Sawant
authors.forename: Binu
authors.initials: B
authors.lastname: Tharakan
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Hunter
authors.forename: Ed W
authors.initials: EW
authors.lastname: Childs
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002317:Cardiovascular Agents / Q000627:therapeutic use; D015195:Drug Design; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; D002317:Cardiovascular Agents