title: Autophagy Portends the Level of Cardiac Hypertrophy in Experimental Hypertensive Swine Model.
abstract: BACKGROUND
  Left ventricular (LV) hypertrophy (LVH) plays an important role in hypertensive heart disease, and may be accompanied by myocardial autophagy. However, the pattern of autophagy during evolution of LVH is unclear. We hypothesized that autophagy activation indicates advancing cardiac LVH with tissue remodeling.
  
  
  METHODS
  Ten domestic pigs with a 10-week unilateral renovascular hypertension (HTN) were classified as mild or moderate HTN (n = 5 each group) based on the degree of renal artery stenosis (above or below 75%). Seven normal pigs served as controls. Left ventricular remodeling, function, and microvascular density were assessed using multi-detector- and micro-computed tomography and histology. Markers of myocardial autophagic and endoplasmic reticulum (ER) stress-related unfolded protein response (UPR), apoptosis, and fibrosis were examined ex vivo.
  
  
  RESULTS
  Both HTN groups had increased myocyte cross-sectional area, but it was greater in moderate HTN, accompanied by elevated LV muscle-mass. Moderate, but not mild HTN, also showed impaired microvascular density and impaired myocardial perfusion. Autophagy mediators were unaltered in mild HTN but UPR markers were increased, while in moderate HTN they were all upregulated, whereas UPR markers were suppressed. Myocardial apoptosis and fibrosis were also greater in moderate HTN. Autophagic proteins were correlated with LVH and fibrosis.
  
  
  CONCLUSIONS
  Autophagic activity is stimulated during the exacerbation of LVH, following a transient early increase in ER stress, and may be involved in the progression of cardiac remodeling in renovascular hypertensive heart disease.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Gibson
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;
authors.forename: Zi-Lun
authors.initials: ZL
authors.lastname: Li
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA. lerman.lilach@mayo.edu.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D001343:Autophagy; D006332:Cardiomegaly / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D002452:Cell Count; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D061330:Multidetector Computed Tomography; D032383:Myocytes, Cardiac / Q000000981:diagnostic imaging / Q000473:pathology*; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology*; D055114:X-Ray Microtomography
keywords: autophagy; blood pressure; hypertension; left ventricular hypertrophy; renal artery stenosis; renin-angiotensin-aldosterone system; unfolded protein response.