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Abstract: FR-PO341

Mitochondrial NADP+ Dependent Isocitrate Dehydrogenase (IDH2) Deficiency Aggravates High Fat Diet-Induced Hypertension

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Noh, Mi Ra, School of Medicine, Kyungpook National University, Daegu, Korea (the Republic of)
  • Kong, Min Jung, Kyungpook Nationcal University, Daegu, DaeJeon, Korea (the Republic of)
  • Kim, Jee in, Keimyung University, Daegu, Korea (the Republic of)
  • Park, Kwon Moo, Kyungpook National University, Daegu, Korea (the Republic of)
Background

Obesity is a major risk factor for essential hypertension. Oxidative stress is an important pathogenic mechanism of obesity-induced hypertension. Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) plays as a major antioxidant system by production of NADPH, which is an essential player in the glutathione (GSH) and thioredoxin systems for peroxide detoxification antioxidant system. Here, we investigated the role of IDH2 in high fat diet (HFD)-induced hypertension using Idh2 gene-deleted (Idh2–/–) mice and wild-type (Idh2+/+) littermates.

Methods

Eight-week-old Idh2–/–and Idh2+/+ mice were fed a normal diet (ND) or a HFD for 12 weeks.

Results

HFD accelerated the increase in body weight and mean blood pressure (MBP) compared to those in the ND group in both mice. MBP was higher in Idh2–/– mice than in Idh2+/+. Also, the level of cholesterol was greater in Idh2–/– mice than in Idh2+/+ mice. Whereas, the lipid accumulation in the kidney was greater in Idh2+/+ HFD mice than in Idh2–/– HFD mice. mRNA levels of renin, angiotensinogen, angiotensin converting enzyme, and angiotensin II receptor type I increased in the HFD mouse kidneys and these increases were higher in Idh2–/– mouse kidneys than in Idh2+/+ mouse kidneys. However, there were no differences in this renin angiotensin system between ND groups. Mitochondrial damage was observed after HFD feeding in both mice and this damage was more severe in the Idh2–/– mice than Idh2+/+ mice.

Conclusion

These results indicate that HFD-induced hypertension is worsened by IDH2 gene deletion with greater oxidative stress in the kidneys, suggesting that mitochondrial redox balance is associated with obesity-induced hypertension.