Background: Thromboangiitis obliterans (TAO), also called Buerger's disease, is a chronic peripheral vascular occlusive disease. It is an obliterative vasculitis characterized by arterial thrombosis and strongly associated with tobacco exposure. The pathogenesis and etiology of TAO are not well understood, but genetic factors may be important in its development. A case-control study was undertaken to identify genetic factors potentially involved in the pathogenesis of TAO in a Xinjiang Uyghur population of China, where TAO is common. Methods: We ascertained 177 TAO patients by clinical screening and 86 healthy individuals from the HAPMAP database. The genotypes of single-nucleotide polymorphisms (SNPs) of the participants were identified using the Affymetrix Genome-Wide Human SNP Array 6.0 to perform a genome wide association study (GWAS). The association between the SNPs and incidence of TAO was quantified using race stratification exposure. Results: Through a case-control GWAS study 26 SNPs were significantly associated with incidence of TAO following a Bonferroni correction. However, after genomic control correction for population stratification only three of these SNPS were highly significantly associated with TAO: rs376511 in IL17RC (OR = 24.4, 95% CI:8.68 -68.62, p < 0.0001), rs7632505 in SEMA5B (OR = 29.47, 95% CI:7.16 -121.3, p < 0.0001), and rs10178082 (OR = 18.09, 95% CI: 6.56 -49.92, p < 0.0001) showed a significant risk of TAO in the Uyghur population. Conclusions: This study shows an association between these 3 SNPs and susceptibility to TAO in the Uyghur population, suggesting that polymorphisms in the IL-17RC and Sema 5B genes may pre-dispose individuals in this population to development of TAO. These findings require replication.

Massive hemorrhage caused by the uncontrolled release of thrombolysis drugs is a key issue of thrombolysis therapy in clinical practice. In this study, we report a near-infrared (NIR) light-triggered drug delivery system, i.e., CuS@mSiO2-PEG (CSP) nanoparticles, for the loading of a thrombolytic drug (urokinase plasminogen activators, uPA). CSP nanoparticles with the CuS nanoparticles as photothermal agents and mesoporous SiO2 for the loading of uPA were synthesized using a facile hydrothermal method. The CSP core-shell nanoparticles were demonstrated to possess excellent photothermal performance, exhibiting a photothermal conversion efficiency of up to 52.8%. Due to the mesoporous SiO2 coating, the CSP core-shell nanoparticles exhibited appropriate pore size, high pore volume, and large surface area; thus, they showed great potential to be used as drug carriers. Importantly, the release of uPA from CuS@mSiO2-PEG/uPA (CSPA) carriers can be promoted by the NIR laser irradiation. The drug loading content of uPA for the as-prepared NIR-triggered drug delivery system was calculated to be 8.2%, and the loading efficiency can be determined to be as high as 89.6%. Due to the excellent photothermal effect of CSP nanocarriers, the NIR-triggered drug delivery system can be used for infrared thermal imaging in vivo. The in vivo thrombolysis assessment demonstrated that the NIR-triggered drug delivery system showed excellent thrombolytic ability under the irradiation of an 808 nm laser, showing the combined therapy for thrombolysis. As far as we know, the CSPA core-shell nanoparticles used as NIR-triggered drug delivery systems for thrombolysis have not been reported.

No abstract

Lower extremity deep vein thrombosis (DVT) is a common peripheral vascular disease, in which inflammation plays an important role. The aim of the present study was to investigate the expression and role of inflammatory factors in DVT. A rat model of venous thrombosis of the lower extremities was established through venous ligation surgery. The rats were examined at 2, 8, 24, 48 and 72 h after the induction of inferior venous stenosis and compared with control and sham surgery groups. The serum levels of interleukin-1β (IL-1β), tissue factor (TF) and xanthine oxidase (XOD) were measured using ELISAs. The morphology of the DVT tissue was observed by hematoxylin and eosin staining. Circulating endothelial cells (CECs) in peripheral blood were counted by flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to detect mRNA and protein expression, respectively. The serum levels of IL-1β, TF and XOD exhibited no significant differences between the control and sham surgery groups. However, those in the rat model of DVT presented an upward trend from 2 to 24 h and peaked at 24 h, with a significant difference from the respective levels in the control and sham surgery groups. The histopathological analysis revealed the presence of red and mixed thrombi in the rats 2-48 h following the induction of inferior venous stenosis group with inflammatory cell infiltration in the vascular wall. Thrombus formation was evident after 72 h. While significant difference was observed in the number of CECs in the peripheral blood between the control and sham surgery groups, the number of peripheral blood CECs in the rats with inferior venous stenosis group increased from 8 to 72 h, with significant differences among these groups. The mRNA levels of IL-1β, TF, XOD and NF-κB in the tissues peaked at 24 h, with significant differences compared with those in the control and sham surgery groups. In addition, the protein expression level of NF-κB increased from 2 to 72 h. In conclusion, these results suggest that the high expression of IL-1β, TF, XOD and NF-κB may promote thrombus formation.