RESUMO
BACKGROUND: Deep vein thrombosis (DVT) is a common vascular surgical disease caused by the coagulation of blood in the deep veins, and predominantly occur in the lower limbs. Endothelial progenitor cells (EPCs) are multi-functional stem cells, which are precursors of vascular endothelial cells. EPCs have gradually evolved into a promising treatment strategy for promoting deep vein thrombus dissolution and recanalization through the stimulation of various physical and chemical factors. METHODS: In this study, we utilized a mouse DVT model and performed several experiments including qRT-PCR, Western blot, tube formation, wound healing, Transwell assay, immunofluorescence, flow cytometry analysis, and immunoprecipitation to investigate the role of HOXD9 in the function of EPCs cells. The therapeutic effect of EPCs overexpressing HOXD9 on the DVT model and its mechanism were also explored. RESULTS: Overexpression of HOXD9 significantly enhanced the angiogenesis and migration abilities of EPCs, while inhibiting cell apoptosis. Additionally, results indicated that HOXD9 specifically targeted the HRD1 promoter region and regulated the downstream PINK1-mediated mitophagy. Interestingly, intravenous injection of EPCs overexpressing HOXD9 into mice promoted thrombus dissolution and recanalization, significantly decreasing venous thrombosis. CONCLUSIONS: The findings of this study reveal that HOXD9 plays a pivotal role in stimulating vascular formation in endothelial progenitor cells, indicating its potential as a therapeutic target for DVT management.
Assuntos
Modelos Animais de Doenças , Células Progenitoras Endoteliais , Proteínas de Homeodomínio , Mitofagia , Neovascularização Fisiológica , Trombose Venosa , Animais , Células Progenitoras Endoteliais/metabolismo , Camundongos , Trombose Venosa/metabolismo , Trombose Venosa/genética , Trombose Venosa/terapia , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Mitofagia/genética , Neovascularização Fisiológica/genética , Movimento Celular , Masculino , Apoptose , Humanos , AngiogêneseRESUMO
Objective To investigate the relationship of androgen receptor (AR) CAG repeat polymorphism and coronary artery disease (CAD) in elderly men and its potential mechanism.Methods Totally 296 elderly men undergoing coronary angiography were enrolled in this study.Serum total testosterone (TT) and free testosterone (FT) levels were measured.Androgen receptors (ARs) in peripheral lymphocytes were determined by flow cytometry.Genome DNA was extracted from peripheral leucocytes using standard techniques.Gene fragments containing AR CAG repeats were amplified by PCR with specific fluorescent labeled primers.PCR products were separated with agarose gels.CAG repeat number of each sample was obtained by genotyping.Results AR CAG repeats varied from 11 to 28 (P25-P75:18-22; median:20) in elderly male patients.They were divided into the long AR group (CAG repeats≥22,n=82) and the short AR group (CAG repeats＜22,n=214).Compared with the long AR group,serum FT level was much lower in the short AR group [(24.1±23.1) ×10-6mmol/L vs.(31.2±27.8)×10-6mmol/L,P＜0.05].The prevalence of coronary artery disease was higher in the short AR group than in the long AR group [84.1％ (180 cases) vs.69.5％(57 cases),P＜0.05].The FT level was lower in the short AR group combined with CAD than in the control group [(22.4±20.5) ×10-6mmol/L vs.(33.6±32.4)×10 6mmol/L,P＜0.01].There were no significant differences in serum TT and AR levels between the long and short AR groups.No significant correlations were found in the AR CAG repeats polymorphism with FT,TT or AR levels.Age was the main risk factor for FT and AR levels.Logistic regression analysis showed that FT level was negatively correlated with CAD (OR=0.98,95 ％ CI:0.973-0.998,P=0.01),and short AR increased the risk of CAD in elderly male patients (OR=3.44,95％CI:1.887-6.264,P＜0.01).Conclusions Serum FT level is correlated with age and is significantly decreased in elderly male patients with short AR repeats,which may increase the risk of CAD in elderly men.
RESUMO
Objective To investigate the effects of ageing on the expression of peroxisome proliferat or-activated receptor (PPAR)? and explore the relation with insulin resistance (IR).Methods Minimal model technique of Bergman was used to estimate the insulin sensitivity of young (10-12 weeks) and aged (24 months) SD rat. The PPAR?mRNA levels of omental fat were measured by reverse transcription-polymerase chain reaction(RT -PCR) and PPAR? protein level were determined by western blotting respectively . Results The level of IR in the aged group was significantly increased compared with tha t of the young group(IR: 11 49?6 92 vs 5 28?1 94,P