Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis, leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies, and surgical specimens of abdominal aortic aneurysms (AAAs) from patients with EH were used. Cell-based assays, NETs/human aortic endothelial cell cocultures, and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly diagnosed patients with EH. Stimulation of control neutrophils with plasma from patients with untreated EH generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via an ROS/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced substantially in patients with EH starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAAs. These data reveal the important pathogenic role of an Ang II/ROS/NET/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.
18 June 2014 in CardioVascular and Interventional Radiology
Purpose: Thoracic endovascular aortic aneurysm repair (TEVAR) has emerged as an attractive alternative option in the treatment of thoracoabdominal aortic aneurysm (TAAA) diseases, reporting lower morbidity and mortality rates compared with open or hybrid repair. A challenging situation arises when the aneurysm involves the celiac artery (CA), precluding a safe distal landing zone. We investigated the safety and efficacy of CA coverage in the treatment of complex TAAA diseases during endovascular management. Materials and Methods: A review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The electronic bibliographic sources searched were MEDLINE and SCOPUS databases. Primary outcomes of interest were perioperative and 30-day mortality. Any type of endoleak, mesenteric ischemia, perioperative spinal cord ischemia, and reintervention rates were secondary end points. A random-effects meta-analysis was performed. Summary statistics of event risks were expressed as proportions and 95% confidence interval (CI). Results: Ten observational cohort studies published between 2009 and 2020, reporting a total of 175 patients, were eligible for quantitative synthesis. Indications for TEVAR were primary TAAAs in 82% of patients, aortic dissection in 14% of patients, type Ib endoleak after previous endograft deployment in 3% of patients, and penetrating aortic ulcer in 1 patient. Reintervention rate was 9% (95% CI, 4%–20%) and spinal cord ischemia was 7% (95% CI, 4%–-12%). Type II endoleak was the predominant type of endoleak in 10% of patients (95% CI, 4%–22%), followed by type I endoleak in 5% of patients (95% CI, 2%–12%) and type III endoleak in 1% (95% CI, 0%–16%) of patients. Mesenteric ischemia occurred in 6% of patients (95% CI, 3%–10%). Thirty-day mortality was 5% (95% CI, 2%–13%) and the pooled estimate for overall mortality was 21% (95% CI, 14%–31%). Conclusions: Celiac artery coverage during TEVAR is a challenging but feasible option for the treatment of TAAA diseases, providing acceptable morbidity and mortality rates. Demonstration of adequate visceral collateral pathways before definitive CA coverage is the sine quo non for the success of the technique.