Kidney Week

Abstract: FR-PO197

Atherosclerosis Is Associated with a Reduction in the Density of Renal Microcirculation

Session Information

• Vascular Biology and Dysfunction
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

• 1103 Vascular Biology and Dysfunction

Authors

• Hueso, Miguel, Hospital Universitari de Bellvitge, Barcelona, Spain

Miguel Hueso,

• Casas Parra, Angela Isabel, Hospital Universitari de Bellvitge, Barcelona, Spain

Angela Isabel Casas Parra,

• Navarro, Estanislao, IDIBELL, L'Hospitalet, Spain

Estanislao Navarro,

• Bolanos, Nuria, IDIBELL, L'Hospitalet, Spain

Nuria Bolanos,

• Varela, Cristian, IDIBELL, L'Hospitalet, Spain

Cristian Varela,

• Ripoll, Elia, Laboratory of Experimental Nephrology, IDIBELL. Hospital Universitari de Bellvitge, Barcelona, Spain

Elia Ripoll,

• Grinyo, J., Hospital Universitari de Bellvitge, Barcelona, Spain

J. Grinyo,

• Cruzado, Josep M., Hospital Universitari de Bellvitge, Barcelona, Spain

Josep M. Cruzado,

• Torras, Juan, Hospital Universitari de Bellvitge, Barcelona, Spain

Juan Torras,

Background

Cardiovascular disease is increased in renal diseases but the role of renal microcirculation in the development of atherosclerosis is unknown. CD40/CD40L signaling has a critical role in atherosclerosis and CD40 silencing reduces their progression. In addition, CD40/CD40L signaling may lead to blood vessel dysfunction and occlusion. Thus, we used the CD40-silenced ApoE^-/- model of atherosclerosis to study the interplay between atherosclerosis and renal microcirculation.

Methods

CD40 was silenced with a specific siRNA in the ApoE^-/- mouse model during 16 weeks. We administrated scrambled siRNA (SC) or PBS (vehicle) as controls. Endothelium was identified by immunohistochemistry using PECAM-1 antibody (platelet endothelial cell adhesion molecule-1). Kidneys were isolated from 24 weeks-old mice. The density of peritubular capillaries was quantified using ImageJ v1.48 and expressed as a proportion. The extension of atherosclerotic lesions was quantified in HE staining from ascending aortas.

Results

SiRNA-CD40 treated ApoE^-/- mice reduced the extension of atherosclerotic lesions in ApoE^-/- mice. Furthermore, a decrease of renal microcirculation density was observed in this experimental model of atherosclerosis (siRNA-CD40, n=9, 4.5±2.2%; SC, n=4, 2.1±0.8 %; Vehicle, n=9, 2.0±1.4%, p<0.0001). No differences in serum creatinine was detected (siRNA-CD40: 0.6±0.18 mg/dL; SC: 0.54±0.2 mg/dL; Vehicle: 0.51±0.3 mg/dL, p=ns).

Conclusion

A reduction in peritubular capillaries was associated with severe atherosclerosis lesions. This data provide structural basis of renal disease in patients with atherosclerosis.