title: Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.
abstract: BACKGROUND
  Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome.
  
  
  METHODS
  Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD).
  
  
  RESULTS
  There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group.
  
  
  CONCLUSIONS
  Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Rabya
authors.initials: R
authors.lastname: Saraf
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Feroze
authors.initials: F
authors.lastname: Mahmood
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Khurram
authors.initials: K
authors.lastname: Owais
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Amit
authors.initials: A
authors.lastname: Bardia
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kamal R
authors.initials: KR
authors.lastname: Khabbaz
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Senthilnathan
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.|Department of Surgery, Rhode Island Hospital, Brown Alpert School of Medicine, Providence, Rhode Island, United States of America.
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Lassaletta
authors.affiliation: Department of Surgery, Rhode Island Hospital, Brown Alpert School of Medicine, Providence, Rhode Island, United States of America.
authors.forename: Frank
authors.initials: F
authors.lastname: Sellke
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Robina
authors.initials: R
authors.lastname: Matyal
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005355:Fibrosis; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051898:Smad1 Protein / Q000378:metabolism; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; D051898:Smad1 Protein; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3