Apolipoprotein E deficient rats generated via zinc-finger nucleases exhibit pronounced in-stent restenosis

• Published in: Scientific reports 2019-12, Vol.9 (1), p.18153-11, Article 18153
• Main Authors: Cornelissen, Anne, Simsekyilmaz, Sakine, Liehn, Elisa, Rusu, Mihaela, Schaaps, Nicole, Afify, Mamdouh, Florescu, Roberta, Almalla, Mohammad, Borinski, Mauricio, Vogt, Felix
• Format: Article
• Language: English
• Subjects: 692/4019/592/75/593/2728; 692/699/75/2099; Abdomen; Animal models; Animals; Aorta; Aorta, Abdominal - metabolism; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - deficiency; Apolipoproteins E - metabolism; Arteriosclerosis; Atherosclerosis; Atherosclerosis - metabolism; Cholesterol; Cholesterol, HDL - metabolism; Cholesterol, LDL - metabolism; Coronary Restenosis - metabolism; Coronary vessels; Diet; Disease Models, Animal; Drug-Eluting Stents; High density lipoprotein; Humanities and Social Sciences; Implants; Low density lipoprotein; Male; multidisciplinary; Neointima - metabolism; Nuclease; Phenotypes; Rats; Rats, Sprague-Dawley; Restenosis; Risk Factors; Rodents; Science; Science (multidisciplinary); Stents; Zinc Finger Nucleases - metabolism; Zinc finger proteins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-54541-z

The long-term success of coronary stent implantation is limited by in-stent restenosis (ISR). In spite of a broad variety of animal models available, an ideal high-throughput model of ISR has been lacking. Apolipoprotein E ( apoE ) deficient rats enable the evaluation of human-sized coronary stents while at the same time providing an atherogenic phenotype. Whereas apoE deficient rats have been proposed as animal model of atherosclerosis, to date it is unknown whether they also develop pronounced ISR. We sought to assess ISR after abdominal aorta stent implantation in apoE deficient rats. A total of 42 rats (16 wildtype, 13 homozygous apoE −/− and 13 heterozygous apoE +/− rats) underwent abdominal aorta stent implantation. After 28 days blood samples were analyzed to characterize lipid profiles. ISR was assessed by histomorphometric means. Homozygous apoE −/− rats exhibited significantly higher total cholesterol and low-density cholesterol levels than wildtype apoE +/+ and heterozygous apoE +/− rats. ISR was significantly pronounced in homozygous apoE −/− rats as compared to wildtype apoE +/+ (p =