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Int J Cardiol. 2016 Jul 15;215:364-71. doi: 10.1016/j.ijcard.2016.04.029. Epub 2016 Apr 12.

HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits.

Author information

1
Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada.
2
Montreal Heart Institute, Université de Montréal, Montreal, Canada.
3
Cerenis Therapeutics, Inc., Ann Arbor, Michigan, USA.
4
Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada. Electronic address: jean-claude.tardif@icm-mhi.org.

Abstract

OBJECTIVES:

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.

KEYWORDS:

Echocardiography-Doppler; High-density lipoprotein; Inflammation; Left ventricular diastolic dysfunction

PMID:
27128563
DOI:
10.1016/j.ijcard.2016.04.029
[Indexed for MEDLINE]

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