title: Graft microvascular disease in solid organ transplantation.
abstract: Alloimmune inflammation damages the microvasculature of solid organ transplants during acute rejection. Although immunosuppressive drugs diminish the inflammatory response, they do not directly promote vascular repair. Repetitive microvascular injury with insufficient regeneration results in prolonged tissue hypoxia and fibrotic remodeling. While clinical studies show that a loss of the microvascular circulation precedes and may act as an initiating factor for the development of chronic rejection, preclinical studies demonstrate that improved microvascular perfusion during acute rejection delays and attenuates tissue fibrosis. Therefore, preservation of a functional microvasculature may represent an effective therapeutic strategy for preventing chronic rejection. Here, we review recent advances in our understanding of the role of the microvasculature in the long-term survival of transplanted solid organs. We also highlight microvessel-centered therapeutic strategies for prolonging the survival of solid organ transplants.
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA, xinguoj@stanford.edu.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Yon K
authors.initials: YK
authors.lastname: Sung
authors.forename: Wen
authors.initials: W
authors.lastname: Tian
authors.forename: Jin
authors.initials: J
authors.lastname: Qian
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
authors.forename: Mark R
authors.initials: MR
authors.lastname: Nicolls
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006801:Humans; D055806:Microvessels / Q000276:immunology / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000276:immunology; D018919:Neovascularization, Physiologic; D016377:Organ Transplantation / Q000009:adverse effects*; D013927:Thrombosis; D014652:Vascular Diseases / Q000209:etiology*; D066253:Vascular Remodeling / Q000276:immunology