Journal article

Publication year: 2011

Pages: 263-270

Journal: Transplantation

Volume number: 91

Issue number: 3

ISSN: 0041-1337

eISSN: 1534-6080

Open access status: Bronze

DOI Link: https://doi.org/10.1097/TP.0b013e3182038654

Publisher: Lippincott, Williams & Wilkins

Abstract: 

Background. Chronic allograft vasculopathy (CAV) is an important aspect of chronic allograft injury, which limits the long-term success of renal transplantation. The pathogenesis of CAV is ill defined, and no effective therapies exist. Acute rejection episodes are a major risk factor for CAV. Recently, we demonstrated that leukocytes, which strongly accumulate in allograft blood vessels during fatal acute rejection, produce acetylcholine (ACh), which has the potential to provoke CAV. Herein, we test the hypothesis that ACh is also produced by leukocytes during the development of CAV.

Methods. Kidneys were transplanted in the Fischer 344 to Lewis rat strain combination, an established experimental model for CAV. Isografts were performed in Lewis rats. The capacity of intravascular graft leukocytes to synthesize ACh was investigated during reversible acute rejection on day 9 posttransplantation and during the process of vascular remodeling on day 42. Furthermore, allograft recipients were treated with rivastigmine, which blocks enzymatic degradation of ACh.

Results. The protein expression of the high-affinity choline transporter-1 and choline acetyltransferase was increased in leukocytes from allografts on day 9 and 42 posttransplantation. In addition, leukocytes accumulating in the lumina of allograft blood vessels were by far more numerous compared with isografts. In line with our hypothesis, ACh itself was detected by high-pressure liquid chromatography in graft leukocytes but not in leukocytes from untreated kidneys. Treatment with rivastigmine drastically exacerbated CAV compared with placebo.

Conclusion. We suggest that endogenous ACh contributes to the pathogenesis of CAV and may be a promising target for novel therapies preventing CAV.

Harvard Citation style: Wilczynska, J., Pfeil, U., Zakrzewicz, A., Dietrich, H., Koerner, C., Hecker, A., et al. (2011) Acetylcholine and Chronic Vasculopathy in Rat Renal Allografts, Transplantation, 91(3), pp. 263-270. https://doi.org/10.1097/TP.0b013e3182038654

APA Citation style: Wilczynska, J., Pfeil, U., Zakrzewicz, A., Dietrich, H., Koerner, C., Hecker, A., Wessler, I., Padberg, W., Kummer, W., & Grau, V. (2011). Acetylcholine and Chronic Vasculopathy in Rat Renal Allografts. Transplantation. 91(3), 263-270. https://doi.org/10.1097/TP.0b013e3182038654