Perturbation of intracellular ion homeostasis is a major cellular stress signal for activation of NLRP3 inflammasome signaling that results in caspase-1 mediated production of IL-1β and pyroptosis. However, the relative contributions of decreased cytosolic [K+] versus increased cytosolic [Ca2+] remain disputed and incompletely defined. We investigated roles for elevated cytosolic [Ca2+] in NLRP3 activation and downstream inflammasome signaling responses in primary murine dendritic cells and macrophages in response to two canonical NLRP3 agonists (ATP and nigericin) that facilitate primary K+ efflux by mechanistically distinct pathways or the lysosome-destabilizing agonist Leu-Leu-O-methyl ester (LLME). The study provides three major findings relevant to this unresolved area of NLRP3 regulation. First, increased cytosolic [Ca2+] was neither a necessary nor sufficient signal for the NLRP3 inflammasome cascade during activation by endogenous ATP-gated P2X7 receptor channels, the exogenous bacterial ionophore nigericin, or the lysosomotropic agent LLME. Second, agonists for three Ca2+-mobilizing G protein-coupled receptors (formyl peptide receptor/FPR; P2Y2 purinergic receptor/P2Y2R; calcium-sensing receptor/CaSR) expressed in murine dendritic cells were ineffective as activators of rapidly induced NLRP3 signaling when directly compared to the K+ efflux agonists. Third, the intracellular Ca2+ buffer, BAPTA, and the channel blocker, 2-aminoethoxydiphenyl borate (2-APB), widely used reagents for disruption of Ca2+-dependent signaling pathways, strongly suppressed nigericin-induced NLRP3 inflammasome signaling via mechanisms dissociated from their canonical or expected effects on Ca2+ homeostasis. The results indicate that the ability of K+ efflux agonists to activate NLRP3 inflammasome signaling can be dissociated from changes in cytosolic [Ca2+] as a necessary or sufficient signal.

Pseudoaneurysm development after carotid endarterectomy is a rare occurrence. Even rarer is pseudoaneurysm formation associated with a distal carotid artery stenosis. We report the case of stent grafting of a carotid artery pseudoaneurysm and tandem high-grade distal stenosis through a transcarotid approach with active flow reversal. No reported cases of a transcarotid artery approach to address a carotid artery aneurysm with tandem stenosis were found in the literature. We show that it may be a safe alternative to a transfemoral artery approach or open surgery. (J Vasc Surg Cases and Innovative Techniques 2020;6:136-9.)

Venous stenting was introduced in the 1990s and has continued to evolve to become the first-line therapy for symptomatic iliofemoral venous outflow pathology. There are several dedicated venous stents available in addition to Boston Scientific’s Wallstent and Cook’s Z-Stent. Numerous studies from tertiary referral centres, as well as industry-sponsored trials, have demonstrated the safety and efficacy of these endovascular devices for non-thrombotic iliac vein (NIVL) and post-thrombotic syndrome (PTS) lesions. Patients presenting with acute deep venous thrombosis (aDVT) may also undergo stenting following thrombus removal. The standard of care for NIVL, PTS and aDVT patients has become venography and intravascular ultrasound, and if an underlying iliofemoral stenosis is identified, a stent is placed. There is a concern that inflammation may affect the results of stenting in the aDVT population. Although endovascular stenting for acute venous diseases appears promising and safe, there is a paucity of data on efficacy in aDVT patients. There are only two industry-sponsored trials and a few publications and presentations at academic society meetings to examine. This review assesses the available results for endovascular stenting for aDVT and PTS patients, but not for NIVL.

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