Coexisting renal artery stenosis and metabolic syndrome magnifies mitochondrial damage, aggravating poststenotic kidney injury in pigs

Arash Aghajani Nargesi, Lihong Zhang, Hui Tang, Kyra L. Jordan, Ishran M. Saadiq, Stephen C. Textor, Lilach O. Lerman, Alfonso Eirin

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Objective:Renovascular disease (RVD) produces chronic underperfusion of the renal parenchyma and progressive ischemic injury. Metabolic abnormalities often accompany renal ischemia, and are linked to poorer renal outcomes. However, the mechanisms of injury in kidneys exposed to the ischemic and metabolic components of RVD are incompletely understood. We hypothesized that coexisting renal artery stenosis (RAS) and metabolic syndrome (MetS) would exacerbate mitochondrial damage, aggravating poststenotic kidney injury in swine.Methods:Domestic pigs were studied after 16 weeks of either standard diet (Lean) or high-fat/high-fructose (MetS) with or without superimposed RAS (n=6 each). Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in vivo with multidetector-CT, and renal tubular mitochondrial structure, homeostasis and function and renal injury ex vivo.Results:Both RAS groups achieved significant stenosis. Single-kidney RBF and GFR were higher in MetS compared with Lean, but decreased in Lean+RAS and MetS+RAS vs.Their respective controls. MetS and RAS further induced changes in mitochondrial structure, dynamics, and function, and their interaction (diet×ischemia) decreased matrix density, mitophagy, and ATP production, and lead to greater renal fibrosis.Conclusion:Coexisting RAS and MetS synergistically aggravate mitochondrial structural damage and dysfunction, which may contribute to structural injury and dysfunction in the poststenotic kidney. These observations suggest that mitochondrial damage precedes loss of renal function in experimental RVD, and position mitochondria as novel therapeutic targets in these patients.

Original languageEnglish (US)
Pages (from-to)2061-2073
Number of pages13
JournalJournal of hypertension
Volume37
Issue number10
DOIs
StatePublished - Oct 1 2019

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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