Acetylcholine and chronic vasculopathy in rat renal allografts.
Transplantation
; 91(3): 263-70, 2011 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-21233792
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Vasculares
/
Acetilcolina
/
Trasplante de Riñón
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Transplantation
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania