Detection of Atherosclerosis by Small RNA-Sequencing Analysis of Extracellular Vesicle Enriched Serum Samples

Atherosclerosis can occur throughout the arterial vascular system and lead to various diseases. Early diagnosis of atherosclerotic processes and of individual disease patterns would be more likely to be successful if targeted therapies were available. For this, it is important to find reliable biomarkers that are easily accessible and with little inconvenience for patients. There are many cell culture, animal model or tissue studies that found biomarkers at the microRNA (miRNA) and mRNA level describing atherosclerotic processes. However, little is known about their potential as circulating and liquid biopsy markers in patients. In this study, we examined serum-derived miRNA – profiles from 129 patients and 28 volunteers to identify potential biomarkers. The patients had four different atherosclerotic manifestations: abdominal aneurysm (n = 35), coronary heart disease (n = 34), carotid artery stenosis (n = 24) and peripheral arterial disease (n = 36). The samples were processed with an extracellular vesicle enrichment protocol, total-RNA extraction and small RNA-sequencing were performed. A differential expression analysis was performed bioinformatically to find potentially regulated miRNA biomarkers. Resulting miRNA candidates served as a starting point for an overrepresentation analysis in which relevant target mRNAs were identified. The Gene Ontology database revealed relevant biological functions in relation to atherosclerotic processes. In patients, expression of specific miRNAs changed significantly compared to healthy volunteers; 27 differentially expressed miRNAs were identified. We were able to detect a group-specific miRNA fingerprint: miR-122-5p, miR-2110 and miR-483-5p for abdominal aortic aneurysm, miR-370-3p and miR-409-3p for coronary heart disease, miR-335-3p, miR-381-3p, miR493-5p and miR654-3p for carotid artery stenosis, miR-199a-5p, miR-215-5p, miR-3168, miR-582-3p and miR-769-5p for peripheral arterial disease. The results of the study show that some of the identified miRNAs have already been associated with atherosclerosis in previous studies. Overrepresentation analysis on this data detected biological processes that are clearly relevant for atherosclerosis, its development and progression showing the potential of these miRNAs as biomarker candidates. In a next step, the relevance of these findings on the mRNA level is to be investigated and substantiated

First experience using intraoperative contrast-enhanced ultrasound during endovascular aneurysm repair for infrarenal aortic aneurysms

BackgroundEndovascular aortic repair (EVAR) has become an additional treatment option for patients with infrarenal aortic aneurysms and suitable aortic morphology. However, endoleaks are commonly encountered and represent a relevant risk for secondary treatment failure. In addition, impaired renal function or allergic reactions to intravascular iodine application might represent exclusion criteria for conventional infrarenal endovascular aortic repair using intraoperative angiography with iodine contrast media. Real-time contrast-enhanced ultrasound (CEUS) with a low mechanical index (MI) is a promising method recently introduced for follow up after endovascular infrarenal aortic repair.MethodsIn this study, intraoperative CEUS using SonoVue as ultrasound contrast agent was evaluated in 17 patients for localization of the proximal infrarenal landing zone, the distal iliac fixation area, and identification of endoleaks in patients suitable for endovascular aortic repair with an infrarenal aortic neck ≥10 mm and non-aneurysmal common iliac arteries. For comparison, 20 patients were treated by conventional EVAR using intraoperative fluoroscopy and iodine contrast media.ResultsIntraoperative application of contrast-enhanced ultrasound (iCEUS) for identification of the infrarenal landing zone and proximal stent graft release was achieved in 14 out of 17 patients (82.4%), as verified by intraoperative angiography or postinterventional imaging. Intraoperative CEUS-assisted visualization of the distal fixation area proximal to the level of the iliac bifurcation was achieved in 89.3% (25 out of 28 iliac arteries examined) in comparison to intraoperative angiography or postinterventional CEUS, computed tomography (CT), or magnetic resonance (MR) angiography. Three selected patients having contraindications for iodine-based contrast media were treated by iCEUS-assisted EVAR without the use of any iodine contrast during fluoroscopy. Time for exposure to intraoperative radiation, volume of contrast medium used, and the number of intraoperative angiographies and postinterventional CT or MR angiographies were significantly reduced in the iCEUS-assisted EVAR group in comparison to conventional endovascular aortic treatment (P < .002 or less for all parameters). Intraoperative application of CEUS detected more endoleaks than conventional EVAR (8/17 vs 4/20; P = .08) treated by proximal stent graft extension in one symptomatic patient with a type Ia endoleak.ConclusionsIntraoperative CEUS-assisted EVAR in patients with infrarenal aortic aneurysms represents a new option for intraoperative visualization of aortoiliac segments required as proximal or distal fixation zones and identification of endoleaks, especially in those patients with contraindications for usage of iodine-containing contrast agents, in association with a reduction of iodine contrast media used and radiation exposure during fluoroscopy

Type A aortic dissection model to improve endovascular research and technologies.

OBJECTIVE Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment. METHODS Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models. RESULTS Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.9 ± 1.4 cm proximally from the aortic annulus, with a length of 4.6 ± 0.9 cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.63 ± 0.163 cm in the ascending aorta. After stent implantation, this distance decreased to 0.26 ± 0.12 cm. CONCLUSION This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons