Browsing by Author "Lu, Xiao"

Now showing 1 - 6 of 6
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    Distension-Induced Gastric Contraction is Attenuated in an Experimental Model of Gastric Restraint
    (Springer Verlag, 2010-08-13) Lu, Xiao; Guo, Xiaomei; Mattar, Samer G.; Navia, Jose A.; Kassab, Ghassan S.; Biomedical Engineering, School of Engineering and Technology
    Background Gastric distension has important implications for motility and satiety. The hypothesis of this study was that distension affects the amplitude and duration of gastric contraction and that these parameters are largely mediated by efferent vagus stimulation. Methods A novel isovolumic myograph was introduced to test these hypotheses. The isovolumic myograph isolates the stomach and records the pressure generated by the gastric contraction under isovolumic conditions. Accordingly, the phasic changes of gastric contractility can be documented. A group of 12 rats were used under in vivo conditions and isolated ex vivo conditions and with two different gastric restraints (small and large) to determine the effect of degree of restraint. Results The comparison of the in vivo and ex vivo contractility provided information on the efferent vagus mediation of gastric contraction, i.e., the in vivo amplitude and duration reached maximum of 12.6±2.7 mmHg and 19.8±5.6 s in contrast to maximum of 5.7±0.9 mmHg and 7.3±1.3 s in ex vivo amplitude and duration, respectively. The comparison of gastric restraint and control groups highlights the role of distension on in vivo gastric contractility. The limitation of gastric distension by restraint drastically reduced the maximal amplitude to below 2.9±0.2 mmHg. Conclusions The results show that distension-induced gastric contractility is regulated by both central nervous system and local mechanisms with the former being more substantial. Furthermore, the gastric restraint significantly attenuates gastric contractility (decreased amplitude and shortened duration of contraction) which is mediated by the efferent vagus activation. These findings have important implications for gastric motility and physiology and may improve our understanding of satiety.
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    Endothelial actin depolymerization mediates NADPH oxidase-superoxide production during flow reversal
    (American Physiological Society (APS), 2014-01-01) Choy, Jenny S.; Lu, Xiao; Yang, Junrong; Zhang, Zhen-Du; Kassab, Ghassan S.; Department of Biomedical Engineering, Purdue School of Engineering and Technology, IUPUI
    Slow moving blood flow and changes in flow direction, e.g., negative wall shear stress, can cause increased superoxide (O2·−) production in vascular endothelial cells. The mechanism by which shear stress increases O2·− production, however, is not well established. We tested the hypothesis that actin depolymerization, which occurs during flow reversal, mediates O2·− production in vascular endothelial cells via NADPH oxidase, and more specifically, the subunit p47phox. Using a swine model, we created complete blood flow reversal in one carotid artery, while the contralateral vessel maintained forward blood flow as control. We measured actin depolymerization, NADPH oxidase activity, and reactive oxygen species (ROS) production in the presence of various inhibitors. Flow reversal was found to induce actin depolymerization and a 3.9 ± 1.0-fold increase in ROS production as compared with forward flow. NADPH oxidase activity was 1.4 ± 0.2 times higher in vessel segments subjected to reversed blood flow when measured by a direct enzyme assay. The NADPH oxidase subunits gp91phox (Nox2) and p47phox content in the vessels remained unchanged after 4 h of flow reversal. In contrast, p47phox phosphorylation was increased in vessels with reversed flow. The response caused by reversed flow was reduced by in vivo treatment with jasplakinolide, an actin stabilizer (only a 1.7 ± 0.3-fold increase). Apocynin (an antioxidant) prevented reversed flow-induced ROS production when the animals were treated in vivo. Cytochalasin D mimicked actin depolymerization in vitro and caused a 5.2 ± 3.0-fold increase in ROS production. These findings suggest that actin filaments play an important role in negative shear stress-induced ROS production by potentiating NADPH oxidase activity, and more specifically, the p47phox subunit in vascular endothelium.
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    Endothelial barrier dysfunction in diabetic conduit arteries: a novel method to quantify filtration
    (American Physiological Society (APS), 2013-02-01) Lu, Xiao; Huxley, Virginia H.; Kassab, Ghassan S.; Department of Biomedical Engineering, Purdue School of Engineering and Technology, IUPUI
    The endothelial barrier plays an important role in atherosclerosis, hyperglycemia, and hypercholesterolemia. In the present study, an accurate, reproducible, and user-friendly method was used to further understand endothelial barrier function of conduit arteries. An isovolumic method was used to measure the hydraulic conductivity (Lp) of the intact vessel wall and medial-adventitial layer. Normal arterial segments with diameters from 0.2 to 5.5 mm were used to validate the method, and femoral arteries of diabetic rats were studied as an example of pathological specimens. Various arterial segments confirmed that the volume flux of water per unit surface area was linearly related to intraluminal pressure, as confirmed in microvessels. Lp of the intact wall varied from 3.5 to 22.1 × 10−7 cm·s−1·cmH2O−1 over the pressure range of 7–180 mmHg. Over the same pressure range, Lp of the endothelial barrier changed from 4.4 to 25.1 × 10−7 cm·s−1·cmH2O−1. During perfusion with albumin-free solution, Lp of rat femoral arteries increased from 6.1 to 13.2 × 10−7 cm·s−1·cmH2O−1 over the pressure range of 10–180 mmHg. Hyperglycemia increased Lp of the femoral artery in diabetic rats from 2.9 to 5.5 × 10−7 cm·s−1·cmH2O−1 over the pressure range of 20–135 mmHg. In conclusion, the Lp of a conduit artery can be accurately and reproducibly measured using a novel isovolumic method, which in diabetic rats is hyperpermeable. This is likely due to disruption of the endothelial glycocalyx.
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    Influence of Peri-duodenal Non-constrictive Cuff on the Body Weight of Rats
    (Springer US, 2015-02) Lu, Xiao; Mattar, Samer G.; Kassab, Ghassan S.; Department of Biomedical Engineering, School of Engineering and Technology
    Background Weight loss has been found to improve or re- solve cardiovascular comorbidities. There is a significant need for reversible device approaches to weight loss. Methods Non-constrictive cuff (NCC) is made of implantable silicone rubber with an internal diameter greater than the duodenum. Ten or 11 NCC were individually mounted along the duodenum from the pyloric sphincter toward the distal duodenum to cover ~22 mm in the length. Twelve Wistar rats were implanted with NCC, and six served as sham, and both groups were observed over 4 months. Six rats with implant had their NCC removed and were observed for additional 4weeks. Results The food intake decreased from 40.1 to 28.1 g/day after 4 months of NCC implant. The body weight gain decreased from 1.76 to 0.46 g/day after 4 months of NCC implant. The fasting glucose decreased from 87.7 to 75.3 mg/ dl at terminal day. The duodenal muscle layer covered by the NCC increased from 0.133 to 0.334 mm. After 4 weeks of NCC removal, the food intake, body weight gain, and fasting glucose recovered to 36.2, 2.51 g/day, and 83.9 mg/dl. The duodenal muscle layer covered by the NCC decreased to 0.217 mm. Conclusion The NCC implant placed on the proximal duode- num is safe in rats for a 4-month period. The efficacy of the NCC implant is significant for decrease in food intake, body weight gain, and fasting glucose in a normal rat model. The removal of NCC implant confirmed a cause-effect relation with food intake and hence body weight.
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    Regulation of 130kDa smooth muscle myosin light chain kinase expression by an intronic CArG element
    (2013) Chen, Meng; Zhang, Wenwu; Lu, Xiao; Hoggatt, April M.; Gunst, Susan J.; Kassab, Ghassan S.; Tune, Johnathan D.; Herring, B. Paul; Department of Cellular & Integrative Physiology, IU School of Medicine
    The mylk1 gene encodes a 220-kDa nonmuscle myosin light chain kinase (MLCK), a 130-kDa smooth muscle MLCK (smMLCK), as well as the non-catalytic product telokin. Together, these proteins play critical roles in regulating smooth muscle contractility. Changes in their expression are associated with many pathological conditions; thus, it is important to understand the mechanisms regulating expression of mylk1 gene transcripts. Previously, we reported a highly conserved CArG box, which binds serum response factor, in intron 15 of mylk1. Because this CArG element is near the promoter that drives transcription of the 130-kDa smMLCK, we examined its role in regulating expression of this transcript. Results show that deletion of the intronic CArG region from a β-galactosidase reporter gene abolished transgene expression in mice in vivo. Deletion of the CArG region from the endogenous mylk1 gene, specifically in smooth muscle cells, decreased expression of the 130-kDa smMLCK by 40% without affecting expression of the 220-kDa MLCK or telokin. This reduction in 130-kDa smMLCK expression resulted in decreased phosphorylation of myosin light chains, attenuated smooth muscle contractility, and a 24% decrease in small intestine length that was associated with a significant reduction of Ki67-positive smooth muscle cells. Overall, these data show that the CArG element in intron 15 of the mylk1 gene is necessary for maximal expression of the 130-kDa smMLCK and that the 130-kDa smMLCK isoform is specifically required to regulate smooth muscle contractility and small intestine smooth muscle cell proliferation.
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    Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats
    (BMC, 2010-05-19) Lu, Xiao; Guo, Xiaomei; Karathanasis, Sotirios K.; Zimmerman, Karen M.; Onyia, Jude E .; Peterson, Richard G.; Kassab, Ghassan S.; Biomedical Engineering, School of Engineering and Technology
    Objectives Endothelial dysfunction precedes atherogenesis and clinical complications in type 2 diabetes. The vascular dysfunction in Zucker diabetic fatty (ZDF) rats was evaluated at different ages along with the effect of treatment with rosiglitazone (Rosi) on endothelial function and mechanical remodeling. Methods The Rosi treatment was given to ZDF rats for 3 weeks. The endothelium-dependent vasodilation and α-adrenoceptor-dependent vasoconstriction of femoral arteries were studied using an ex-vivo isovolumic myograph. The biomechanical passive property of the arteries was studied in Ca2+-free condition. The expressions of endothelial nitric oxide synthase (eNOS), α-adrenoceptor, matrix metalloproteinase 9 (MMP9), and elastase were evaluated. Results Endothelium-dependent vasorelaxation of the femoral artery was blunted at low doses in ZDF rats at 11 weeks of age and attenuated at all doses in ZDF rats at 19 weeks of age. The expression of eNOS was consistent with the endothelium-dependent vasorelaxation. The α-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of α-adrenoceptor, MMP9, and elastase were up regulated in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks restored endothelium-dependent vasorelaxation and the expression of eNOS and the adrenoceptor activation at the doses below 10-6 mole/L in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks did not, however, improve the mechanical properties of blood vessel, the expressions of α-adrenoceptor, MMP9, and elastase in ZDF rats. Conclusion The endothelial dysfunction and mechanical remodeling are observed as early as 19 weeks of age in ZDF rat. Rosi treatment for 3 weeks improves endothelial function but not mechanical properties.