Immunosuppression With FTY720 Reverses Cardiac Dysfunction in Hypomorphic ApoE Mice Deficient in SR-BI Expression That Survive Myocardial Infarction Caused by Coronary Atherosclerosis

Journal of Cardiovascular Pharmacology
Fu Sang LukRobert L Raffai

Abstract

We recently reported that immunosuppression with FTY720 improves cardiac function and extends longevity in Hypomorphic ApoE mice deficient in scavenger receptor Type-BI expression, also known as the HypoE/SR-BI(–/–) mouse model of diet-induced coronary atherosclerosis and myocardial infarction (MI). In this study, we tested the impact of FTY720 on cardiac dysfunction in HypoE/SR-BI(–/–) mice that survive MI and subsequently develop chronic heart failure. HypoE/SR-BI(–/–) mice were bred to Mx1-Cre transgenic mice, and offspring were fed a high-fat diet (HFD) for 3.5 weeks to provoke hyperlipidemia, coronary atherosclerosis, and recurrent MIs. In contrast to our previous study, hyperlipidemia was rapidly reversed by inducible Cre-mediated gene repair of the HypoE allele and switching mice to a normal chow diet. Mice that survived the period of HFD were subsequently given oral FTY720 in drinking water or not, and left ventricular (LV) function was monitored using serial echocardiography for up to 15 weeks. In untreated mice, LV performance progressively deteriorated. Although FTY720 treatment did not initially prevent a decline of heart function among mice 6 weeks after Cre-mediated gene repair, it almost completely restored norma...Continue Reading

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Citations

Mar 24, 2017·American Journal of Physiology. Renal Physiology·Carla S CeronDavid H Lovett
May 24, 2018·Journal of Cardiovascular Development and Disease·Laura Bouchareychas, Robert L Raffai
Nov 14, 2017·Current Pharmacology Reports·Eric K KwongHuiping Zhou
Jul 6, 2019·Cardiology Research and Practice·Nan-Bo LiuXiao-Kang Li
Apr 30, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Sven HermannMichael Schäfers

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