title: HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits.
abstract: OBJECTIVE
  High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis in rabbits but their effect on ventricular function remains unknown. We aimed to evaluate the effects of the HDL mimetic peptide CER-522 on left ventricular diastolic dysfunction (LVDD).
  
  
  METHODS
  Rabbits were fed with a cholesterol- and vitamin D2-enriched diet until mild aortic valve stenosis and hypercholesterolemia-induced LV hypertrophy and LVDD developed. Animals then received saline or 10 or 30mg/kg CER-522 infusions 6 times over 2weeks. We performed serial echocardiograms and LV histology to evaluate the effects of CER-522 therapy on LVDD.
  
  
  RESULTS
  LVDD was reduced by CER-522 as shown by multiple parameters including early filling mitral deceleration time, deceleration rate, Em/Am ratio, E/Em ratio, pulmonary venous velocities, and LVDD score. These findings were associated with reduced macrophages (RAM-11 positive cells) in the pericoronary area and LV, and decreased levels of apoptotic cardiomyocytes in CER-522-treated rabbits. CER-522 treatment also resulted in decreased atheromatous plaques and internal elastic lamina area in coronary arteries.
  
  
  CONCLUSIONS
  CER-522 improves LVDD in rabbits, with reductions of LV macrophage accumulation, cardiomyocyte apoptosis, coronary atherosclerosis and remodelling.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Merlet
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Busseuil
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Teodora
authors.initials: T
authors.lastname: Mihalache-Avram
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Mecteau
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Walid
authors.initials: W
authors.lastname: Nachar
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Brand
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Mathieu R
authors.initials: MR
authors.lastname: Brodeur
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Charpentier
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Rhainds
authors.affiliation: Cerenis Therapeutics, Inc., Ann Arbor, Michigan, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Sy
authors.affiliation: Cerenis Therapeutics, Inc., Ann Arbor, Michigan, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Schwendeman
authors.affiliation: Cerenis Therapeutics, Inc., Ann Arbor, Michigan, USA.
authors.forename: Narendra
authors.initials: N
authors.lastname: Lalwani
authors.affiliation: Cerenis Therapeutics, Inc., Ann Arbor, Michigan, USA.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dasseux
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Rhéaume
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada. Electronic address: jean-claude.tardif@icm-mhi.org.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000139:chemically induced / Q000503:physiopathology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D008075:Lipoproteins, HDL / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D057786:Peptidomimetics / Q000008:administration & dosage* / Q000494:pharmacology; D011817:Rabbits; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D008075:Lipoproteins, HDL; D057786:Peptidomimetics; D002784:Cholesterol
keywords: Echocardiography-Doppler; High-density lipoprotein; Inflammation; Left ventricular diastolic dysfunction