Systematic review and meta-analysis of type B aortic dissection involving the left subclavian artery with a Castor stent graft.

Objective: Despite the rapid development of thoracic endovascular aortic repair (TEVAR), it is still a challenge to maintain the blood flow of the branch arteries above the aortic arch in Stanford type B aortic dissection involving the left subclavian artery (LSA). The Castor stent graft is an integrated, customized, single-branch stent that enables reconstruction of the LSA. The purpose of this systematic review and meta-analysis was to assess the efficacy of the Castor stent graft for type B aortic dissection. Materials and methods: An extensive electronic literature search (PROSPERO registration number: CRD42022322146) was undertaken to identify all articles published up to August 2022 that described thoracic aortic repair with branch stents in the treatment of type B aortic dissection involving the LSA. The quality of the included studies was analyzed using the MINORS criteria. The primary outcome measures were the technical success rate, early mortality rate, endoleak rate, and 1-year survival rate. The secondary outcome measures were the stroke rate, left upper extremity ischemia rate, and target vessel patency rate. Results: Eleven studies involving 415 patients were eligible for this meta-analysis. The LSA was successfully preserved in all procedures. The technical success rate was 97.5% (95% CI: 0.953-0.991); the intraoperative endoleak rate was 0.1% (95% CI: 0.000-0.012); the intraoperative LSA patency rate was 99.52%; the intraoperative LSA stent deformation and stenosis rate was 0.15% (95% CI: 0.000-0.051); the early type I endoleak rate was 1.6% (95% CI: 0.003-0.035); the 30-day mortality rate was 0.96%; the early reintervention rate was 0.9% (95% CI: 0.000-0.040); and the perioperative stroke rate was 0% (95% CI: 0.000-0.005). The 1-year survival rate was 99.7% (95% CI: 0.976-1.000). The half-year LSA patency rate was 99.3%, the 1-year LSA patency rate was 97.58%, and the 2-year LSA patency rate was 95.23%. During the follow-up period, the leakage rate was 0.3% (95% CI: 0.000-0.017), the incidence of left upper extremity ischemia rate was 0.5% (95% CI: 0.000-0.035), and the deformation and stenosis rate of the LSA stent was 2.2% (95% CI: 0.06-0.046). Conclusion: This meta-analysis shows that endovascular repair of type B aortic dissection using the Castor stent-graft may be technically feasible and effective. However, this conclusion needs to be interpreted with caution, as the quality of evidence for all outcomes is between low and very low. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022322146].

CD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis.

Type 2 diabetes mellitus (T2D) contributes to sustained inflammation and myopathic changes in the heart although the precise interplay between the two remains largely unknown. This study evaluated the impact of deficiency in CD74, the cognate receptor for the regulatory cytokine macrophage migration inhibitory factor (MIF), in T2D-induced cardiac remodeling and functional responses, and cell death domains involved. WT and CD74-/- mice were fed a high fat diet (60% calorie from fat) for 8 weeks prior to injection of streptozotocin (STZ, 35 mg/kg, i.p., 3 consecutive days) and were maintained for another 8 weeks. KEGG analysis for differentially expressed genes (DEGs) reported gene ontology term related to ferroptosis in T2D mouse hearts. T2D patients displayed elevated plasma MIF levels. Murine T2D exerted overt global metabolic derangements, cardiac remodeling, contractile dysfunction, apoptosis, pyroptosis, ferroptosis and mitochondrial dysfunction, ablation of CD74 attenuated T2D-induced cardiac remodeling, contractile dysfunction, various forms of cell death and mitochondrial defects without affecting global metabolic defects. CD74 ablation rescued T2D-evoked NLRP3-Caspase1 activation and oxidative stress but not dampened autophagy. In vitro evidence depicted that high glucose/high fat (HGHF) compromised cardiomyocyte function and promoted lipid peroxidation, the effects were ablated by inhibitors of NLRP3, pyroptosis, and ferroptosis but not by the mitochondrial targeted antioxidant mitoQ. Recombinant MIF mimicked HGHF-induced lipid peroxidation, GSH depletion and ferroptosis, the effects of which were reversed by inhibitors of MIF, NLRP3 and pyroptosis. Taken together, these data suggest that CD74 ablation protects against T2D-induced cardiac remodeling and contractile dysfunction through NLRP3/pyroptosis-mediated regulation of ferroptosis.

Beclin1 haploinsufficiency rescues low ambient temperature-induced cardiac remodeling and contractile dysfunction through inhibition of ferroptosis and mitochondrial injury.

OBJECTIVE: Cold exposure provokes cardiac remodeling and cardiac dysfunction. Autophagy participates in cold stress-induced cardiovascular dysfunction. This study was designed to examine the impact of Beclin1 haploinsufficiency (BECN+/-) in cold stress-induced cardiac geometric and contractile responses. METHODS AND MATERIALS: Wild-type (WT) and BECN+/- mice were assigned to normal or cold exposure (4 °C) environment for 4 weeks prior to evaluation of cardiac geometry, contractile and mitochondrial properties. Autophagy, apoptosis and ferroptosis were evaluated. RESULTS: Our data revealed that cold stress triggered cardiac remodeling, compromised myocardial contractile capacity including ejection fraction, fractional shortening, peak shortening and maximal velocity of shortening/relengthening, duration of shortening and relengthening, intracellular Ca2+ release, intracellular Ca2+ decay, mitochondrial ultrastructural disarray, superoxide production, unchecked autophagy, apoptosis and ferroptosis, the effects of which were negated by Beclin1 haploinsufficiency. Circulating levels of corticosterone were elevated in both WT and BECN+/- mice. Treatment of corticosterone synthesis inhibitor metyrapone or ferroptosis inhibitor liproxstatins-1 rescued cold stress-induced cardiac dysfunction and mitochondrial injury. In vitro study noted that corticosterone challenge compromised cardiomyocyte function, provoked lipid peroxidation and mitochondrial injury, the effects of which were nullified by Beclin1 haploinsufficiency, inhibitors of lipoxygenase, ferroptosis and autophagy. In addition, ferroptosis inducer erastin abrogated Beclin1 deficiency-offered cardioprotection. CONCLUSION: These data suggest that Beclin1 haploinsufficiency protects against cold exposure-induced cardiac dysfunction possibly through corticosterone- and ferroptosis-mediated mechanisms.