Endovascular procedures cause transient endothelial injury but do not disrupt mature neointima in Drug Eluting Stents

Extensive application of coronary intravascular procedures has led to the increased need of understanding the injury inflicted to the coronary arterial wall. We aimed to investigate acute and prolonged coronary endothelial injury as a result of guidewire use, repeated intravascular imaging and stenting. These interventions were performed in swine (N = 37) and injury was assessed per coronary segment (n = 81) using an Evans Blue dye-exclusion-test. Scanning electron microscopy and light microscopy were then used to visualize the extent and nature of acute (<4 hours) and prolonged (5 days) endothelial injury. Guidewire and imaging injury was mainly associated with denudation and returned to control levels at 5 days. IVUS and OCT combined (Evans Blue staining 28 ± 16%) did not lead to more acute injury than IVUS alone (33 ± 15%). Stent placement caused most injury (85 ± 4%) and despite early stent re-endothelialization at 5 days, the endothelium proved highly permeable (97 ± 4% at 5 days; p < 0.001 vs acute). Imaging of in-stent neointima at 28 days after stent placement did not lead to neointimal rupture. Guidewire, IVUS and OCT induce acute endothelial cell damage, which does not increase during repeated imaging, and heals within 5 days. Interestingly, endothelial permeability increases 5 days post stenting despite near complete re-endothelialization

In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review

__Background__ Multiple inducers of in vitro Neutrophil Extracellular Trap (NET) formation (NETosis) have been described. Since there is much variation in study design and results, our aim was to create a systematic review of NETosis inducers and perform a standardized in vitro study of NETosis inducers important in (cardiac) wound healing. __Methods__ In vitro NETosis was studied by incubating neutrophils with PMA, living and dead bacteria (S. aureus and E. coli), LPS, (activated) platelets (supernatant), glucose and calcium ionophore Ionomycin using 3-hour periods of time-lapse confocal imaging. __Results__ PMA is a consistent and potent inducer of NETosis. Ionomycin also consistently resulted in extrusion of DNA, albeit with a process that differs from the NETosis process induced by PMA. In our standardized experiments, living bacteria were also potent inducers of NETosis, but dead bacteria, LPS, (activated) platelets (supernatant) and glucose did not induce NETosis. __Conclusion__ Our systematic review confirms that there is much variation in study design and results of NETosis induction. Our experimental results confirm that under standardized conditions, PMA, living bacteria and Ionomycin all strongly induce NETosis, but real-time confocal imaging reveal different courses of events

Angiographic and Optical Coherence Tomography Insights into Bioresorbable Scaffold Thrombosis: Single-Center Experience

Background - As bioresorbable vascular scaffolds (BVSs) are being increasingly used in complex real-world lesions and populations, BVS thrombosis cases have been repo

High-Resolution Imaging of Interaction Between Thrombus and Stent-Retriever in Patients With Acute Ischemic Stroke

BACKGROUND: Currently, acute ischemic stroke is still a leading cause of mortality and morbidity. Approximately 2 years ago, mechanical thrombectomy was proven beneficial as a revolutionary new therapy for stroke in the MR-CLEAN trial (A Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). However, the mechanisms by which the thrombectomy device, or stent-retriever, interacts with the thrombus are largely unknown. A better understanding could lead to improved efficacy of mechanical thrombectomy devices. METHODS AND RESULTS: Seven stent-retrievers with thrombi still entrapped were collected directly after thrombectomy. The stent-retrievers were studied using micro computed tomography, followed by scanning electron microscopy and light microscopy. Two independent observers rated interaction type and thrombus surface structure (porous filamentous or dense) at the interaction sites.A total of 79 interaction sites between thrombus and stent-retriever were categorized. Thrombus-stent-retriever interaction was found to be adhesive (n=44; 56%) or mechanical (n=35; 44%). Adhesive interaction was most frequently observed at interaction sites with a dense surface, compared with interaction sites with a porous filamentous fibrin surface (38/58; 66% versus 6/21; 29%, P=0.011). CONCLUSIONS: The interaction between thrombus and stent-retriever was predominantly adhesive, not mechanical. Adhesive interaction was strongly associated with the presence of a dense thrombus surface without a porous filamentous fibrin network

Association between plaque vulnerability and neutrophil extracellular traps (NETs) levels: The Plaque At RISK study

Carotid atherosclerotic plaque rupture and its sequelae are among the leading causes of acute ischemic stroke. The risk of rupture and subsequent thrombosis is, among others, determined by vulnerable plaque characteristics and linked to activation of the immune system, in which neutrophil extracellular traps (NETs) potentially play a role. The aim of this study was to investigate how plaque vulnerability is associated with NETs levels. We included 182 patients from the Plaque At RISK (PARISK) study in whom carotid imaging was performed to measure plaque ulceration, fibrous cap integrity, intraplaque hemorrhage, lipid-rich necrotic core, calcifications and plaque volume. Principal component analysis generated a 'vulnerability index' comprising all plaque characteristics. Levels of the NETs marker myeloperoxidase-DNA complex were measured in patient plasma. The association between the vulnerability index and low or high NETs levels (dependent variable) was assessed by logistic regression. No significant association between the vulnerability index and NETs levels was detected in the total population (odds ratio 1.28, 95% confidence interval 0.90-1.83, p = 0.18). However, in the subgroup of patients naive to statins or antithrombotic medication prior to the index event, this association was statistically significant (odds ratio 2.08, 95% confidence interval 1.04-4.17, p = 0.04). Further analyses revealed that this positive association was mainly driven by intraplaque hemorrhage, lipid-rich necrotic core and ulceration. In conclusion, plaque vulnerability is positively associated with plasma levels of NETs, but only in patients naive to statins or antithrombotic medication prior to the index event