Kidney Week

Abstract: FR-PO333

Peroxisome Proliferator-Activated Receptor α Attenuates Hypercholesterolemia-Induced Serum Sulfatide Abnormalities

Session Information

• Hypertension and CVD: Mechanisms - I
  October 26, 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

• Kamijo, Yuji, Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

Yuji Kamijo,

• Aomura, Daiki, Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

Daiki Aomura,

• Kurihara, Shigekazu, Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

Shigekazu Kurihara,

• Nimura, Takayuki, Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

Takayuki Nimura,

• Harada, Makoto, Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

Makoto Harada,

Background

As chronic kidney disease (CKD) patients often develop accompanying cardiovascular disease (CVD), an understanding of the developmental mechanisms of CVD is important for nephrologists. Our past studies have demonstrated that serum levels of sulfatides, which belong to glycosphingolipids regulated by peroxisome proliferator-acitvated receptor α (PPARα) and exert anti-platelet and anticoagulation activities, were decreased in end-stage CKD patients and that serum levels of sulfatides in CKD patients with CVD were lower than in those without. Thus, reduced serum sulfatides in CKD patients is potentially related to CVD development. It is also unknown whether hypercholesterolemia, an important CKD risk factor, affects serum levels of sulfatides with or without PPARα involvement.

Methods

We fed a high-cholesterol (HC) diet to wild-type (WT) and Ppara-null (KO) mice and examined the serum level changes of cholesterol and sulfatides, sulfatide metabolism, and oxidative stress, another important factor influencing serum sulfatide levels.

Results

The HC diet caused identical levels of hypercholesterolemia in WT and KO mice. Serum levels of sulfatides and the expression level of CST, a major sulfatide synthase, were significantly decreased in both groups due to cholesterol overload, with significantly lower levels in the KO group. On the other hand, oxidative stress was significantly increased in both groups by cholesterol overload, with significantly higher levels in KO mice.

Conclusion

Hypercholesterolemia via cholesterol overload induced a reduction of serum sulfatide levels, suppression of sulfatide synthase expression, and an increase in oxidative stress. PPARα attenuated serum sulfatide abnormalities by maintaining sulfatide synthesis and reducing oxidative stress. PPARα activation therapy may therefore be useful for preventing CVD in CKD patients with hypercholesterolemia.