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Renal Revascularization Attenuates Myocardial Mitochondrial Damage and Improves Diastolic Function in Pigs with Metabolic Syndrome and Renovascular Hypertension

Abstract

Percutaneous transluminal renal angioplasty (PTRA) may improve cardiac function in renovascular hypertension (RVH), but its effect on the biological mechanisms implicated in cardiac damage remains unknown. We hypothesized that restoration of kidney function by PTRA ameliorates myocardial mitochondrial damage and preserves cardiac function in pigs with metabolic syndrome (MetS) and RVH. Pigs were studied after 16 weeks of MetS+RVH, MetS+RVH treated 4 weeks earlier with PTRA, and Lean and MetS Sham controls (n=6 each). Cardiac function was assessed by multi-detector CT, whereas cardiac mitochondrial morphology and function, microvascular remodeling, and injury pathways were assessed ex vivo. PTRA attenuated myocardial mitochondrial damage, improved capillary and microvascular maturity, and ameliorated oxidative stress and fibrosis, in association with attenuation of left ventricular remodeling and diastolic dysfunction. Myocardial mitochondrial damage correlated with myocardial injury and renal dysfunction. Preservation of myocardial mitochondria with PTRA can enhance cardiac recovery, underscoring its therapeutic potential in experimental MetS+RVH.

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Abbreviations

RVH:

Renovascular hypertension

MetS:

Metabolic syndrome

PTRA:

Percutaneous transluminal renal angioplasty

ATP:

Adenosine triphosphate

ROS:

Reactive oxygen species

LV:

Left ventricular

PRA:

Plasma renin activity

MCP:

Monocyte chemoattractant protein

IL:

Interleukin

NT-proBNP:

N-terminal pro-brain natriuretic peptide

MDCT:

Multi-detector computed tomography

LVMM:

LV muscle mass

LA:

Left atrium

RBF:

Renal blood flow

GFR:

Glomerular filtration rate

H202 :

Hydrogen peroxide

COX-IV:

Cytochrome-c oxidase

DHE:

Dihydroethidium

WGA:

Wheat germ agglutinin

EDV:

End-diastolic volume

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Funding

This work was supported by the NIH grants: DK122137, DK104273, DK120292, HL095638, DK118120, and DK102325.

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Correspondence to Alfonso Eirin.

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This article does not contain any studies with human participants. All animal studies were approved by the Mayo Clinic Animal Care and Use Committee.

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Farahani, R.A., Yu, S., Ferguson, C.M. et al. Renal Revascularization Attenuates Myocardial Mitochondrial Damage and Improves Diastolic Function in Pigs with Metabolic Syndrome and Renovascular Hypertension. J. of Cardiovasc. Trans. Res. (2021). https://doi.org/10.1007/s12265-021-10155-3

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Keywords

  • Renovascular hypertension
  • Cardiac dysfunction
  • Metabolic syndrome
  • Mitochondria
  • Revascularization