Inappropriate Activation of TLR4/NF-κB is a Cause of Heart Failure

Significance: Heart failure, a disease with extremely high incidence, is closely associated with inflammation and oxidative stress. The Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway plays an important role in the occurrence and development of heart failure. Recent advances: Previous studies have shown that TLR4/NF-κB causes heart failure by inducing oxidative stress and inflammation; damaging the endothelia; promoting fibrosis; and inducing myocardial hypertrophy, apoptosis, pyroptosis, and autophagy. Critical issues: Understanding the pathogenesis of heart failure is essential for the treatment of this disease. In this review, we outline the mechanisms underlying TLR4/NF-κB pathway-mediated heart failure and discuss drugs that alleviate heart failure by regulating the TLR4/NF-κB pathway. Future directions: During TLR4/NF-κB overactivation, interventions targeting specific receptor antagonists may effectively alleviate heart failure, thus providing a basis for the development of new anti-heart failure drugs

Controllable Assembly of Vanadium-Containing Polyoxoniobate-Based Three-Dimensional Organic–Inorganic Hybrid Compounds and Their Photocatalytic Properties

The controllable synthesis of two vanadium-containing polyoxoniobate-based three-dimensional organic–inorganic hybrid compounds, [Co­(pn)₂]₄[HPNb₁₀V^IV₂O₄₀(V^IVO)₄]·17H₂O (<b>1</b>) and [Co­(pn)₂]₅[PNb₁₂O₄₀(V^IVO)₆]­(OH)₇·15H₂O (<b>2</b>), where pn = 1,2-diaminopropane, is realized by changing the hydrothermal temperature or adding <i>N</i>-(aminoethyl)­piperazine as an additive. Both compounds <b>1</b> and <b>2</b> are structurally characterized by single-crystal/powder X-ray diffraction and IR and X-ray photoelectron spectroscopy. Compound <b>1</b> features a new divanadium-substituted Keggin polyoxoniobate capped by four vanadyl groups, and the polyanion in <b>2</b> exhibits the highest coordination number (10-connected) in polyoxoniobate chemistry. Moreover, the photocatalytic activities of <b>1</b> and <b>2</b> for hydrogen evolution are preliminarily assessed

Table_1_Repair effect of the poly (D,L-lactic acid) nanoparticle containing tauroursodeoxycholic acid-eluting stents on endothelial injury after stent implantation.docx

BackgroundChronic endoplasmic reticulum stress (ERS) plays a crucial role in cardiovascular diseases. Thus, it can be considered a therapeutic target for these diseases. In this study, poly (D,L-lactic acid) (PDLLA) nanoparticle-eluting stents loaded with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, was fabricated to assess their ability to reduce endothelial cell apoptosis and promote re-endothelialization after stent implantation.Materials and methodsPDLLA nanoparticles loaded with TUDCA were prepared via the emulsification-solvent evaporation method. The cumulative release rates of TUDCA were measured in vitro via high-performance liquid chromatography. The carotid arteries of rabbits were subsequently implanted with stents in vivo. The rabbits were then sacrificed after 4 weeks for scanning electron microscopy. Meanwhile, TUDCA concentration in the homogenate of the peripheral blood and distal vascular tissue after stent implantation was measured. The effect of TUDCA on ERS, apoptosis, and human umbilical vein endothelial cell (HUVEC) function was investigated in vitro by performing cell migration assay, wound healing assay, cell proliferation assays, endoplasmic reticulum (ER)-specific fluorescence staining, immunofluorescence, and western blotting.ResultsTUDCA nanoparticles were released slowly over 28 days. In addition, TUDCA-eluting stents enhanced re-endothelialization and accelerated the recovery of endotheliocytes in vivo. ERS and apoptosis significantly increased in H2O2-treated HUVECs in vitro. Meanwhile, TUDCA reduced apoptosis and improved function by inhibiting ERS in H2O2-treated HUVECs. Decreased rates of apoptosis and ERS were observed after silencing XBP-1s in H2O2-treated HUVECs.ConclusionTUDCA can inhibit apoptosis and promote re-endothelialization after stent implantation by inhibiting IRE/XBP1s-related ERS. These results indicate the potential therapeutic application of TUDCA as a drug-coated stent.</p