Well-functioning endothelium is critical for a healthy graft after solid organ transplantation. In the context of transplantation, microvascular endothelial cells (ECs) are very susceptible to injury, including episodes of acute rejection (AR). These repetitive insults target the microvasculature and ultimately lead to the development of interstitial fibrosis and tubular atrophy (IFTA).Whether AR is associated with sustained systemic microvascular damage is unknown. Recently, Sidestream Darkfield (SDF) imaging has emerged as a non-invasive tool to visualize the human microcirculation. We assessed the systemic effects of AR on EC damage up to 1 year after rejection and correlated this with markers for endothelial dysfunction.
Capillary morphology was visualized using SDF imaging of the oral mucosa. Microvascular alterations in AR (n=16) and IFTA (n=15) patients were compared with stable KTx recipients (n=15). In addition, 11 AR patients were studied longitudinally during AR, 1 (M1), 6 (M6) and 12 (M12) months after AR. Circulating levels of growth factors that regulate microvascular structure, including Angiopoietin-1 (Ang-1) and Angiopoietin-2(Ang-2) were measured using ELISA and the Ang-2/Ang-1 ratio was calculated as a more optimal reflection of microvascular function.
Capillary tortuosity was significantly increased in AR patients (mean 1.74±0.5, SEM) and IFTA (1.95±0.3) compared with the stable group (1.40±0.2, p<0.05). Furthermore, the Ang-2/Ang-1 ratio was significantly increased in patients with AR (0.09±0.01) compared with stable patients (0.05±0.01, p<0.05). Interestingly, AR patients in the longitudinal study showed increased capillary tortuosity at 1 (1.76±0.1),6 (1.88±0.2) and 12 (1.73±0.1) months after AR compared to stable patients (all p<0.05) and a disturbed Ang-2/Ang-1 balance up to 1 year after AR (0.08±0.02).
Our study demonstrates that AR is associated with systemic microvascular destabilization up to 1 year after rejection. Since angiopoietins are considered important microvascular modulators, restoration of the Ang-2/Ang-1 balance might represent a potential therapeutic strategy for microvascular stabilization after rejection.
To cite this abstract in AMA style:Khairoun M, Ocak G, Rotmans J, Vries Ade, Berg Bvanden, Lievers E, Mallat M, Vries Dde, Zonneveld Avan, Fijter Jde, Rabelink T, Reinders M. Acute Rejection Is Associated with Increased Microvascular Tortuosity and a Dysbalance in Angiopoietins up to 1 Year after Rejection [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/acute-rejection-is-associated-with-increased-microvascular-tortuosity-and-a-dysbalance-in-angiopoietins-up-to-1-year-after-rejection/. Accessed May 6, 2021.
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