title: Differential modulation of AMPK/PPARα/UCP2 axis in relation to hypertension and aging in the brain, kidneys and heart of two closely related spontaneously hypertensive rat strains.
abstract: OBJECTIVE
  We examined expression protein of AMPK/SIRT1/PGC1α/PhoxO3a/PPARα/UCP2 pathway in brain, kidneys and heart of stroke-prone spontaneously hypertensive rat (SHRSP) vs stroke-resistant SHR (SHRSR) at different weeks of age, up to one year, in order to test the hypothesis that abnormalities within this pathway could associate with higher susceptibility of SHRSP to develop hypertension-related vascular damage.
  
  
  BACKGROUND
  SHRSP develops severe hypertension and related target organ damage. Marked reduction of uncoupling protein 2 (UCP2) expression upon high salt-low potassium diet associates with increased renal injury in SHRSP. UCP2 may represent a key mitochondrial protein involved in cardiovascular damage.
  
  
  RESULTS
  At 2 months of age a significant down-regulation of UCP2 expression at both mRNA and protein levels was found, along with reduced protein expression of all components of UCP2 regulatory pathway, in tissues of SHRSP but not of SHRSR, that progressed with hypertension development and aging. A significant increase of both oxidative stress and inflammation was detected in tissues of SHRSP as a function of age. SBP levels were significantly higher in SHRSP than SHRSR at 3 months of age and thereafter. At one year of age, higher degree of renal damage, with proteinuria and severe glomerular and tubulo-interstitial fibrosis, of cerebral damage, with significant vessel extravasation and stroke occurrence, and of myocardial damage was detected in SHRSP than SHRSR.
  
  
  CONCLUSIONS
  The early significant reduced expression of the antioxidant AMPK/PPARα/UCP2 pathway that progressed throughout lifetime may contribute to explain higher predisposition of SHRSP to oxidative stress dependent target organ damage in the context of severe hypertension.
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S. Andrea, Rome, Italy.|Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Bianchi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Carla Letizia
authors.initials: CL
authors.lastname: Busceti
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cotugno
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Stanzione
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Marchitti
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Di Castro
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Madonna
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.|Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S. Andrea, Rome, Italy.|Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, Pozzilli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D015398:Signal Transduction; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D055372:AMP-Activated Protein Kinases
keywords: Gerotarget; SHRSP; aging; hypertension; target organ damage; uncoupling protein 2