Key result
Cilostazol significantly attenuated aortic intimal hyperplasia in a mouse model of chronic kidney disease, demonstrated by a 34% reduction in total intima area compared to placebo.
Why the study?
Does cilostazol attenuate intimal hyperplasia in a mouse model of chronic kidney disease?
Does cilostazol attenuate intimal hyperplasia in a mouse model of chronic kidney disease?
Effect estimate: 34% reduction
Absolute Event Rate: 99704% vs 150556%
p-value: p=<0.01
Cilostazol significantly attenuated aortic intimal hyperplasia and reduced pro-inflammatory mediators in a normotensive mouse model of chronic kidney disease, suggesting a potential primary prevention strategy for CKD-related vasculopathy.
Attenuates aortic IH in a CKD mouse model; leaves open translation to human prevention strategies.
Intimal hyperplasia (IH) is a common cause of vasculopathy due to direct endothelial damage (such as post-coronary revascularization) or indirect injury (such as chronic kidney disease, or CKD). Although the attenuation of coronary revascularization-induced IH (direct-vascular-injury-induced IH) by cilostazol, a phosphodiesterase III inhibitor, has been demonstrated, our understanding of the effect on CKD-induced IH (indirect-vascular-injury-induced IH) is limited. Herein, we tested if cilostazol attenuated CKD-induced IH in a mouse model of ischemic-reperfusion injury with unilateral nephrectomy (Chr I/R), a normotensive non-proteinuria CKD model. Cilostazol (50 mg/kg/day) or placebo was orally administered once daily from 1-week post-nephrectomy. At 20 weeks, cilostazol significantly attenuated aortic IH as demonstrated by a 34% reduction in the total intima area with 50% and 47% decreases in the ratios of tunica intima area/tunica media area and tunica intima area/(tunica intima + tunica media area), respectively. The diameters of aorta and renal function were unchanged by cilostazol. Interestingly, cilostazol decreased miR-221, but enhanced miR-143 and miR-145 in either in vitro or aortic tissue, as well as attenuated several pro-inflammatory mediators, including asymmetrical dimethylarginine, high-sensitivity C-reactive protein, vascular endothelial growth factor in aorta and serum pro-inflammatory cytokines (IL-6 and TNF-α). We demonstrated a proof of concept of the effectiveness of cilostazol in attenuating IH in a Chr I/R mouse model, a CKD model with predominantly indirect-vascular-injury-induced IH. These considerations warrant further investigation to develop a new primary prevention strategy for CKD-related IH.
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Chancharoenthana et al. (2017) studied Chronic kidney disease (ischemic-reperfusion injury with unilateral nephrectomy) (n=26). Cilostazol vs. Placebo was evaluated on Total intima area (μm²) (34% reduction, p=<0.01). Cilostazol significantly attenuated aortic intimal hyperplasia in a mouse model of chronic kidney disease, demonstrated by a 34% reduction in total intima area compared to placebo.
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