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Abstract: FR-OR078

Experimental Renovascular Disease Induces Endothelial Cell Mitochondrial Damage and Impairs Endothelium-Dependent Relaxation of Renal Artery Segments

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Aghajani Nargesi, Arash, Mayo Clinic, Rochester, Minnesota, United States
  • Jordan, Kyra L., Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Amir, Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic College of Medicine, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States
Background

Endothelial cell (EC) mitochondria produce energy, control redox status, and support EC function, but may be damaged during renal disease. We hypothesized that the ischemic and metabolic constituents of swine renovascular disease (RVD) induce mitochondrial damage and impair the function of renal artery EC.

Methods

Domestic pigs were studied after 16 weeks of diet-induced metabolic syndrome (MetS), renal artery stenosis (RAS), or coexisting MetS and RAS, and Lean pigs served as control (n=6 each). Mitochondrial morphology (electron microscopy), membrane potential (TMRE staining), and production of reactive oxygen species (MitoSOX) were measured in isolated primary renal artery EC. Vasoreactivity of renal artery segments was characterized in an organ bath.

Results

Lean-RAS and MetS-RAS developed significant stenosis and hypertension (Table), and showed increased mitochondrial area and decreased matrix density (Fig. A). Mitochondrial membrane potential similarly decreased in MetS, Lean+RAS, and MetS+RAS groups, whereas production of reactive oxygen species increased in MetS vs. Lean, but further increased in both RAS groups (Fig. B). Endothelial-dependent relaxation of renal artery segments was blunted in MetS vs. Lean, but further attenuated in Lean+RAS and MetS+RAS (Fig. C).

Conclusion

MetS and RAS damage mitochondria in pig renal artery EC, which may impair EC function. However, the coexistence of MetS and RAS did not aggravate EC mitochondrial injury and dysfunction in the short time of our in-vivo studies. These findings suggest that mitochondrial injury might be implicated in the pathogenesis of RVD-induced vascular damage.

Funding

  • NIDDK Support