Biomedical subjects

Zhen W Zhuang

Publications and source records attributed to Zhen W Zhuang.

4 recordsLinked to original sources

PubMed2006

Selective regulation of arterial branching morphogenesis by synectin.

Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched, stunted, and thin intersomitic vessels due to impaired migration and proliferation of angioblasts and arterial endothelial cells while not affecting venous development. Synectin(-/-) mice demonstrated decreased body and organ size, reduced numbers of arteries, and an altered pattern of arterial branching in multiple vascular beds while the venous system remained normal. Murine synectin(-/-) primary arterial, but not venous, endothelial cells showed decreased in vitro tube formation, migration, and proliferation and impaired polarization due to abnormal localization of activated Rac1. We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Arteriogenesis: noninvasive quantification with multi-detector row CT angiography and three-dimensional volume rendering in rodents.

PURPOSE: To evaluate two-dimensional (2D) multi-detector row computed tomographic (CT) angiography and three-dimensional (3D) volume rendering for depiction of patterns of arterial growth and quantification of blood vessel density and volume. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. The right femoral artery and its branches were ligated and excised in 16 inbred Lewis rats; animals were randomly assigned to receive 70 microL Dulbecco's modified Eagle's medium (DMEM) or 1.5 x 10(7) bone marrow-derived mononuclear cells (BMC) from isogenic donor rats in 70 microL DMEM. At 2 weeks, CT angiography was performed with injection of 0.45 mL barium sulfate suspension at 0.7 mL/min, followed by silver staining. Number of blood vessels, area, mean area, volume, and blood vessel size distribution derived from digitally subtracted 2D CT angiographic sections were quantified; 3D images were reconstructed. Two-way analysis of variance and paired and unpaired Student t tests were performed. RESULTS: CT angiography showed two patterns of arterial growth: collateral arterial formation and branching arteriogenesis. Two-way analysis of variance indicated that differences within subjects (ischemic vs nonischemic legs) and between subjects (BMC vs DMEM treatment) were significant for total blood vessel area, total blood vessel volume, and mean of blood vessel area (P < .001). In the BMC group, there were significantly more arteries (mean, 241.6 +/- 77.0 [standard deviation] vs 196.4 +/- 75.2, P = .028), but mean cross-sectional area of these arteries was smaller in ischemic versus nonischemic legs (5.4 mm(2) +/- 1.2 vs 6.8 mm(2) +/- 1.3, P = .006). Total arterial area and volume did not differ significantly between ischemic and nonischemic legs. CONCLUSION: BMC injection had a substantial effect on arteriogenesis, with normalization of total arterial area and volume in the BMC group; this effect was successfully depicted.

Angiography↗

PubMed2005

Delayed arteriogenesis in hypercholesterolemic mice.

BACKGROUND: Hypercholesterolemia has been reported to inhibit ischemia-induced angiogenesis. To address its effects on arteriogenesis, we investigated arterial growth in hypercholesterolemic low-density lipoprotein receptor(-/-)/ApoB-48(-/-) (HCE) mice. METHODS AND RESULTS: The extent and the time course of arteriogenesis after femoral artery ligation was evaluated in HCE and strain-matched control mice. Distal limb perfusion was measured by laser Doppler imaging, whereas MRI was used to visualize arterial flow and micro-computed tomography to assess vascular growth. After femoral artery ligation, serial laser Doppler imaging demonstrated significantly delayed restoration of perfusion in untreated HCE compared with control mice (day 3, 0.09 versus 0.19, P<0.05). Treatment with Ad-PR39 in control mice led to a significant restoration of arterial blood flow and tissue perfusion at day 3, whereas in HCE mice, hindlimb perfusion began increasing only by day 7. Micro-CT analysis confirmed increased growth of smaller arterioles (16 to 63 microm in diameter) in the Ad-PR39-treated control compared with HCE mice. The delay in arteriogenesis in HCE mice correlated with delayed tissue appearance of F4/80+ cells. Analysis of gene expression after Ad-PR39 treatment demonstrated that HCE mice had significantly reduced expression of FGF receptor 1, hypoxia-inducible factor-1alpha, vascular cell adhesion molecule-1, macrophage scavenger receptor-1, and cyclophilin A compared with controls 3 days after arterial ligation that equalized by day 7, mimicking relative changes in arteriogenesis and tissue perfusion. CONCLUSIONS: Hypercholesterolemia results in delayed native arteriogenesis because of reduced early monocyte/macrophage influx and delayed and impaired arterial growth response to growth factor therapy.

Animals↗

PubMed2002

Long-term results and quality of life in patients treated with transjugular intrahepatic portosystemic shunts.

OBJECTIVE: The purpose of our study was to determine long-term survival, shunt patency, and quality of life in patients after creation of a transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: We followed up 103 patients who underwent TIPS for a mean of 20.10 +/- 25.58 months (range, 1 day-92 months). Various statistical methods were used to analyze long-term survival, shunt patency, and correlation with Child-Pugh classification and indications for TIPS. The Rand 36-Item Health Survey 1.0 was used to assess quality of life over time. RESULTS: The cumulative survival rate was 68%, 60%, 50%, 41%, and 41% at years 1-5, respectively. The cumulative survival rate was significantly higher for patients classified as Child-Pugh class A or B versus those classified as class C (p < 0.01), as well as for patients with the original indication of variceal bleeding versus refractory ascites or hydrothorax (p < 0.01). No significant difference in survival rates was found between patients with Child-Pugh A and those with Child-Pugh B. The cumulative primary patency rate was 50%, 34%, 21%, 13%, and 13% at years 1-5, respectively, with assisted patency rate of 80%, 61%, 46%, 42%, and 36%. Cumulative secondary patency rate was 85%, 64%, 55%, 55%, and 55% at years 1-5. Mean follow-up time in 33 patients who completed quality-of-life questionnaires with one follow-up was 17.46 months. Scores after TIPS in all nine of the health categories were higher than those preprocedure with statistically significant improvement in four categories. The second follow-up was completed by 21 patients at a mean of 30.58 months after TIPS creation. Both scores after TIPS were higher than those before TIPS, and scores in five categories were further improved at the second surveillance (p < 0.0, only for health change), whereas in four categories, the scores were slightly worse. CONCLUSION: TIPS has positive efficacy both for controlling bleeding or ascites and for improving the quality of life. The precise impact of TIPS on long-term survival, however, requires further clarification.

Adult↗