Xiaojing Wu

Over-expression of hepatocyte growth factor in smooth muscle cells regulates endothelial progenitor cells differentiation, migration and proliferation

BACKGROUND Endothelial repair is one of key events after vascular injury. The mechanisms by which hepatocyte growth factor (HGF) and endothelial progenitor cells (EPCs) may be responsible for re-endothelialization of injured blood vessel wall are poorly understood. METHODS Primary culture SMCs were transfected with pcDNA3.0-HGF followed by G418 selection, one of G418-resistant colonies in well was picked, propagated and used as donor cells for further experiments. HGF and VEGF expression in SMCs were detected with western blot and enzyme linked immunosorbent assays (ELISA). Rat EPCs were cultured in untreated, pcDNA3.0 and pcDNA3.0-HGF transfected SMCs conditioned medium with or without anti-VEGF or exogenous recombinant HGF addition. eNOS, KDR and CD31 expression in EPCs was determined by real-time quantitative polymerase chain reaction (RT-qPCR) or flow cytometry; EPCs migration and proliferation were measured by using a modified Boyden chambers and MTT assay respectively. RESULTS Abundant and stable expression of HGF was found in G418-resistant colony-derived SMCs. VEGF expression significantly increased in HGF transfected SMCs. Exogenous recombinant HGF (rHGF) markedly up-regulated eNOS mRNA expression in EPCs and promoted EPCs migration and proliferation, but no significant changes were found in KDR and CD31 mRNA expression. HGF transfection in SMCs was more effective than exogenous HGF for EPCs differentiation, proliferation and migration. CONCLUSIONS Over-expression of HGF in SMCs can be helpful for promoting EPCs differentiation, increasing EPCs migration and proliferation. It may be responsible for angiogenesis of arteriosclerosis lesions and useful for blood vessel tissue engineering.

Tailored antiplatelet therapy and clinical adverse outcomes

Objective The clinical evidence regarding the influence of tailored antiplatelet strategy on adverse outcomes has been controversial. The aim of the study was to evaluate the significance of tailored antiplatelet therapy with respect to clinical adverse events in antiplatelet-resistant patients. Methods Randomised studies that assess clinical relevance of personalised antiplatelet treatment in antiplatelet-resistant patients were identified through a literature search: PubMed, EMBASE, Web of Science and the Cochrane Library. The primary endpoint was the composite of death from any cause and stent thrombosis. All total clinical adverse events and bleeding complications were evaluated. Results Data were combined across seven randomised studies comprising 12 048 subjects, of whom 3738 (31.0%) were found to be antiplatelet-resistant. Antiplatelet-resistant patients provided with tailored antiplatelet therapy showed less risk of death or stent thrombosis than those assigned conventional antiplatelet treatment (0.5% vs 2.2%; OR (95% CI) 0.25 (0.13 to 0.49), p<0.0001). A significant benefit in terms of total adverse event risk reduction was observed during follow-up for tailored vs conventional antiplatelet therapy (5.5% vs 10.0%; OR (95% CI) 0.40 (0.20 to 0.77), p=0.006). No statistical difference in bleeding complications was observed between these two groups (p=0.08). Conclusions In the study, personalised antiplatelet treatment for antiplatelet resistance was found to be associated with less occurrence of death or stent thrombosis and the less risk of total clinical adverse events than conventional treatment, without increasing the risk of bleeding complications.

High altitude-induced borderline pulmonary hypertension impaired cardiorespiratory fitness in healthy young men

OBJECTIVE High altitude exposure has been suggested to cause borderline elevation of pulmonary artery pressure (PAP) in quite a few healthy individuals. This cohort study was to investigate the impact of altitude induced borderline pulmonary hypertension (PH) on cardiorespiratory fitness in healthy subjects. METHODS 299 healthy Chinese young men with normal PAP were consecutively studied between July 2011 and September 2013. Among these subjects 114 kept living at low altitude (450m), 91 ascended to high altitude (3700m) from low altitude within 24h (acute exposure), and 94 resided at 3700m for more than 1year (chronic exposure). Mean PAP and cardiac function were examined by echocardiography, and cardiorespiratory fitness was determined by predicted work capacity at a heart rate of 170beats per minute (PWC170). RESULTS Mean PAP remained within normal range (<20mmHg) in 113 of 114 participants (99%) at low altitude. In contrast, the incidence of borderline PH (mPAP between 20 and 25mmHg) was 29% and 37% for respective acute and chronic exposures. Compared to the subjects with normal mPAP within each of the exposure groups, the subjects with borderline PH had increased right ventricular Tei index (RV-Tei), which correlated with the decline of PWC170 (acute exposure: r=-0.296, p=0.004; chronic exposure: r=-0.247, p=0.016). However, these changes were relatively milder than those with confirmed PH (mPAP>25mmHg). CONCLUSION Borderline PH compromised cardiorespiratory fitness in healthy young men. The decline of cardiorespiratory fitness was related at least in part with the impaired right ventricular function, which was correlated with the elevated mPAP.

Aging reduces susceptibility of vascular smooth muscle cells to H2O2-induced apoptosis through the down-regulation of Jagged1 expression in endothelial cells

In addition to excessive proliferation, reduced apoptosis of vascular smooth muscle cells (VSMCs) plays a key role in aging-exaggerated neointima formation after vascular injury. Our previous studies have shown that impaired expression of Jagged1 in the endothelium may be a key event that leads to enhanced VSMC proliferation in the elderly. Here, we are the first to investigate whether the expression of Jagged1 in endothelial cells (ECs) may regulate apoptosis of VSMCs. We discovered that VSMCs co-cultured with senescent ECs exhibited decreased susceptibility to H₂O₂-induced apoptosis compared with those co-cultured with young ECs. Senescent ECs also displayed lower Jagged1 expression compared to young ECs, which was more evident after H₂O₂ stimulation. Overexpression of Jagged1 in senescent ECs significantly promoted H₂O₂-induced apoptosis in the co-cultured VSMCs, whereas silencing Jagged1 expression in young ECs reduced H2O2-induced apoptosis in the co-cultured VSMCs. Our studies also revealed that Jagged1 expressed in ECs exerted its pro-apoptotic activity by lowering expression of the anti-apoptotic protein Bcl-2. These results demonstrate that aging reduces the susceptibility of co-cultured VSMCs to H₂O₂-induced apoptosis through impaired Jagged1 expression in ECs.

Responsiveness to aspirin in patients with unstable angina pectoris by whole blood aggregometry.

Aims:  To evaluate aspirin responsiveness in patients with unstable angina pectoris (UAP) by whole blood aggregometry. Another goal was to differentiate aspirin‐resistant patients into pharmacokinetic or pharmacodynamic type.