implantation-human-sized-coronary-stents-into-rat-abdominal-aorta

Implantation of Human-Sized Coronary Stents into Rat Abdominal Aorta Using a Trans-Femoral Access

Percutaneous coronary intervention (PCI), combined with the deployment of a coronary stent, represents the gold standard in interventional treatment of ...

University Hospital RWTH Aachen

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 = <0.0001) and heterozygous apoE rats (p = 0.0102) on western diet. Abdominal aorta stenting of apoE rats is a reliable model to investigate ISR after stent implantation and thus can be used for the evaluation of novel stent concepts. Apolipoprotein E (apoE) deficient rats have been proposed as animal model of atherosclerosis. We investigated the development of restenosis 28 days after stent implantation into the abdominal aorta of wildtype apoE, homozygous apoE and heterozygous apoE rats, respectively. Homozygous apoE rats exhibited significantly higher LDL and significantly lower HDL cholesterol levels compared to wildtype apoE and heterozygous apoE rats. Restenosis after stent implantation was significantly pronounced in western-diet-fed homozygous apoE rats, accompanied by a significantly increased neointimal thickness. Thus, apoE knockout rats exhibit elevated restenosis and might provide a novel tool for testing of innovative stent concepts.

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

In patients with cardiovascular events, such as myocardial infarction or aortic dissection without known risk factors for cardiovascular disease, neoplastic disease should be considered as a differential diagnosis. In this report, we present a case of a 51-year old man with previously undiagnosed non-small lung cancer leading to fatal cardiovascular complications due to hemovascular spread, diagnosed post-mortem. This case illustrates the value of autopsy in unexpected deaths.

An unusual case of aortic metastasis from lung cancer.

We propose in vitro endothelialization of drug-eluting stents (DES) to overcome late stent thrombosis by directly introducing late-outgrowth human endothelial progenitor cells (EPCs) at the target site utilizing abluminal DES. Isolated EPCs were confirmed as late-outgrowth EPCs by flow cytometric analysis. Abluminally paclitaxel-loaded stents were seeded with different cell concentrations and durations to determine optimal seeding conditions, in both uncrimped and crimped configurations. The seeding yield was determined by evaluating the percent coverage of the stent struts' area. The EPC-seeded DES were exposed to arterial shear stress to evaluate the effect of high shear stress on EPCs. To investigate how much paclitaxel elutes during the seeding procedure, a pharmacokinetic analysis was performed. Finally, to validate the proof of concept, EPC-seeded DES were placed on a fibrin matrix with and without smooth muscle cells (SMCs) and cultured for 3 days under perfusion. The seeding procedure resulted in 47% and 26% coverage of the stent surface in uncrimped and crimped conditions, respectively. After the optimal seeding, almost 99% of drug was still available. When EPC-seeded DES were placed on a fibrin matrix and cultured for 3 days, the EPCs confluently covered the stent surface and spread to the surrounding fibrin gel. When EPC-seeded DES were placed on SMC-containing fibrin layers, cells in contact with the struts died. EPCs can be successfully seeded onto DES without losing drug-eluting capability, and EPCs exhibit sufficient proliferative ability. EPC-seeded DES may combine early re-endothelialization ability with the antirestenotic effectiveness of DES.

Article	Year
Apolipoprotein E deficient rats generated via zinc-finger nucleases exhibit pronounced in-stent restenosis. Scientific reports\| PubMed ID: 31796798	2019
An unusual case of aortic metastasis from lung cancer. Discoveries (Craiova, Romania)\| PubMed ID: 32309623	2020
Development of in vitro endothelialized drug-eluting stent using human peripheral blood-derived endothelial progenitor cells. Journal of tissue engineering and regenerative medicine\| PubMed ID: 32668066	2020

Nicole Schaaps

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