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

Arash Aghajani Nargesi, Xiang Yang Zhu, Ishran M. Saadiq, Kyra L. Jordan, Amir Lerman, Lilach O. Lerman, Alfonso Eirin

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Mitochondria modulate endothelial cell (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 ECs. METHODS: Pigs were studied after 16 weeks of metabolic syndrome (MetS), renal artery stenosis (RAS), or MetS + RAS, and Lean pigs served as control (n = 6 each). Mitochondrial morphology, homeostasis, and function were measured in isolated primary stenotic-kidney artery ECs. EC functions were assessed in vitro, whereas vasoreactivity of renal artery segments was characterized in organ baths. RESULTS: Lean + RAS and MetS + RAS ECs showed increased mitochondrial area and decreased matrix density. Mitochondrial biogenesis was impaired in MetS and MetS + RAS compared with their respective controls. 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. EC tube formation was impaired in MetS, RAS, and MetS + RAS vs. Lean, but EC proliferation and endothelial-dependent relaxation of renal artery segments were blunted in MetS vs. Lean, but further attenuated in Lean + RAS and MetS + RAS. CONCLUSIONS: MetS and RAS damage mitochondria in pig renal artery ECs, which may impair EC function. Coexisting MetS and RAS did not aggravate EC mitochondrial damage in the short time of our in vivo studies, suggesting that mitochondrial injury is associated with impaired renal artery EC function.

Original languageEnglish (US)
Pages (from-to)765-774
Number of pages10
JournalAmerican journal of hypertension
Volume33
Issue number8
DOIs
StatePublished - Aug 4 2020

Keywords

  • blood pressure
  • hypertension
  • metabolic syndrome
  • mitochondria
  • renal artery stenosis
  • renovascular disease

ASJC Scopus subject areas

  • Internal Medicine

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