title: Mitochondrial targeted peptides attenuate residual myocardial damage after reversal of experimental renovascular hypertension.
abstract: BACKGROUND
  Renovascular hypertension (RVHT) increases cardiovascular morbidity and mortality. Renal revascularization with percutaneous transluminal renal angioplasty and stenting (PTRS) may reverse RVHT but may not fully regress cardiac remodeling and damage, possibly due to persistent myocardial insults. Bendavia is a mitochondrial targeted peptide that reduces ischemic cardiomyopathy by improving mitochondrial function. However, its potential for attenuating residual myocardial damage after reversal of RVHT has not been explored. We hypothesized that treatment with Bendavia as an adjunct to PTRS would improve cardiac function and oxygenation, and decrease myocardial injury in swine RVHT.
  
  
  RESULTS
  After 6 weeks of RVHT (unilateral renal artery stenosis) or control, pigs underwent PTRS (or sham), with adjunct continuous infusion of Bendavia (0.05  mg/kg intravenously, 30  min before to 3.5  h after PTRS) or vehicle (n = 7 each). Four weeks later, systolic and diastolic function were assessed by multidetector computed tomography, myocardial oxygenation by blood oxygen level-dependent MRI, and myocardial morphology, apoptosis, mitochondrial biogenesis, and fibrosis evaluated ex vivo. PTRS restored blood pressure in both groups, yet E/A ratio remained decreased. Myocardial oxygenation and mitochondrial biogenesis improved, and myocardial inflammation, oxidative stress, and fibrosis normalized in association with improvement in diastolic function in RVHT + PTRS + Bendavia animals.
  
  
  CONCLUSIONS
  Adjunct Bendavia during PTRS in swine RVHT improved diastolic function and oxygenation and reversed myocardial tissue damage. This approach may allow a novel strategy for preservation of cardiac function and structure in RVHT.
authors.affiliation: aDivision of Nephrology and Hypertension, Department of Internal Medicine bDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Williams
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: John A
authors.initials: JA
authors.lastname: Crane
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D017130:Angioplasty; D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006334:Heart Function Tests; D006978:Hypertension, Renovascular / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D007677:Kidney Function Tests; D055806:Microvessels / Q000648:ultrastructure; D008929:Mitochondria, Heart / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D013552:Swine
chemical_list: D010455:Peptides; D003094:Collagen; D010100:Oxygen
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