Abstract: SA-PO979
Mechanisms Linking CKD and Atherosclerosis: CD34+ Cell in the Atherosclerosis Plaque
Session Information
- Hypertension and CVD: Mechanisms - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Hueso, Miguel, Hospital of Bellvitge, L'Hospitalet de Llobregat (Barcelona), Spain
- Navarro, Estanislao, IDIBELL, Hospitalet de Llobregat, Spain
- Bolanos, Nuria, IDIBELL, Hospitalet de Llobregat, Spain
- Varela, Cristian, IDIBELL, Hospitalet de Llobregat, Spain
- Casas Parra, Angela Isabel, Laboratory Experimental Nephrology, IDIBELL. Hospital Universitari de Bellvitge, Barcelona, Spain
- Guiteras, Jordi, IDIBELL, Hospitalet de Llobregat, Spain
- Torras, Joan, Laboratory Experimental Nephrology, IDIBELL. Hospital Universitari de Bellvitge, Barcelona, Spain
Background
Chronic kidney disease (CKD) is associated with a higher incidence of atherosclerotic vascular disease (ASVD) but its pathogenic mechanism is not well known. CKD is associated with lower circulating CD34+ Endothelial Progenitor Cells (EPCs) and atherosclerotic lesions have a focal distribution suggesting an impaired vascular repair mechanism. The aim of this study was to localize stems and CD34+ EPCs in the vascular wall from humans and in a mouse model of atherosclerosis.
Methods
We assessed CD34 + hematopoietic stem cells in the atherosclerotic plaque by IHQ in the abdominal aorta obtained from 10 human necropsies (5 patients with CKD). CD34 levels were quantified by qPCR. Furthermore, we analyzed CD34+ by IHQ in 10 APOE-/- mice with a CD40 blockade using a specific siRNA (siCD40) and in 10 APOE-/- controls (5 mice treated with scrambled siRNA (SC) and 5 mice treated with vehicle (veh)) at 24 weeks .
Results
We included 18 samples (9 atherosclerotic plaques and 9 samples from normal abdominal aorta without injury) from 9 patients (5 patients with CKD). Atherosclerotic plaque was associated with increased inflammation in the intima (14 ± 15% in the sample without injury, n=9 vs 54 ± 25% in the plaque, n=8, p=0.004). CD34+ cells were increased in the atherosclerotic plaque (-4.7 ± 0.76 cycles, n=6 in normal aorta vs -3.2±1 cycles, n=4 in plaque, p=0.028). Furthermore, we have identified niches of CD34+ cells in the neointima and in the adventitia of human arteries. Then, we analyzed mRNA levels of CD34+ patients in normal vascular walls with CKD and we observed a trend to display lower number of CD34 cells (-4.5±0.7 cycles in non-CKD patients, n=4, -5.3±0.75 cycles in CKD patients, n=2; p=0.3). Finally CD34+ cells were identified especially in the perivascular adipose tissue (PVAT) of mice treated with siCD40 (9±1% in 5 mice treated with veh, 3±2% in 5 mice treated with SC, vs 13±6% in 10 mice treated with siCD40, p<0.0001).
Conclusion
Atherosclerotic plaque is associated with increased inflammation and an increase number of cells hematopoietic stem cells (HSCs)/endothelial progenitor cells (EPCs) CD34+cells. HSCs/EPCs could participate in vascular remodeling (regeneration), but also in the neovascularization that may contribute to plaque growth and its destabilization.
Funding
- Government Support - Non-U.S.