Increased Remnant Lipoproteins in Apo E Deficient Mice Induce Coronary Atherosclerosis following Transverse Aortic Constriction and Aggravate the Development of Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Ilayaraja Muthuramu; Mudit Mishra; Bart De Geest

doi:10.3390/biomedicines10071592

Increased Remnant Lipoproteins in Apo E Deficient Mice Induce Coronary Atherosclerosis following Transverse Aortic Constriction and Aggravate the Development of Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Biomedicines. 2022 Jul 4;10(7):1592. doi: 10.3390/biomedicines10071592.

Authors

Ilayaraja Muthuramu^{1

2}, Mudit Mishra^{1

3

4}, Bart De Geest¹

Affiliations

¹ Centre for Molecular and Vascular Biology, Catholic University of Leuven, 3000 Leuven, Belgium.
² Gene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
³ Department of Cardiothoracic Surgery, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
⁴ Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, 3508 GA Utrecht, The Netherlands.

Abstract

Murine coronary arteries are very resistant to the development of atherosclerosis, which may be related to their intramyocardial course. Blood pressure promotes atherosclerotic plaque formation by acting as a physical force that potentiates the migration of pro-atherogenic lipoproteins across the endothelium. C57BL/6N apolipoprotein (apo) E deficient mice have increased remnant lipoproteins that are a risk factor for coronary atherosclerosis. In this study, our aim was to quantify coronary atherosclerosis and artery remodeling following transverse aortic constriction (TAC) in C57BL/6N apo E^-/- mice and to evaluate the impact of increased remnant lipoproteins on the development of pressure overload-induced cardiac hypertrophy and heart failure. Advanced atherosclerotic lesions were observed in the left coronary artery of C57BL/6N apo E^-/- TAC mice but not in C57BL/6N TAC mice. Pressure overload resulted in markedly increased cardiac hypertrophy and more pronounced heart failure in C57BL/6N apo E^-/- TAC mice in comparison to C57BL/6N TAC mice. Pathological hypertrophy, as evidenced by increased myocardial fibrosis and capillary rarefaction, was more prominent in C57BL/6N TAC apo E^-/- than in C57BL/6N TAC mice and led to more marked cardiac dysfunction. In conclusion, TAC in apo E deficient mice induces coronary atherosclerosis and aggravates the development of pathological cardiac hypertrophy and heart failure.

Keywords: apolipoprotein E; cardiac dysfunction; coronary atherosclerosis; heart failure; oxidative stress; pathological hypertrophy; pressure overload; remnant lipoproteins; transverse aortic constriction.

Abstract

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