Tissue Eng Lecture_102413

Tissue Eng Lecture_102413

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Unformatted text preview: f the multiscale computational FIGURE 3. Summary of computational models of angiogenesis that 7 Angiogenesis steps: Angiogenic stimuli Angiogenesis is initiated outside the bloodstream with a distress signal from the tissue Tissues signal there is a need for new blood vessel growth • • Hypoxic, metabolic, or mechanical stimuli Signal is sensed by the endothelium Angiogenesis results in increased tissue blood flow and oxygenation 8 Angiogenesis steps: Angiogenic stimuli Important signaling pathways involved in stimulating angiogenesis • Hypoxia-inducible factors (HIFs) are involved in oxygen sensing and metabolism • HIF-1 promotes vascular endothelial growth factor (VEGF) • VEGF has been investigated in many systems biology studies 9 Angiogenesis steps: Angiogenic stimuli 10 Angiogenesis steps: Angiogenic stimuli Time scale of microvascular growth in exercising skeletal muscle Muscle activity via stimulation Pre-capillary arterioles Diameter Pressure Early adaptations 2–4 days Dilatation Later adaptations 7 days Dilatation Pressure/ stretch Density of arterioles Shear stress Shear stress Shear stress normalized eNOS, NO nNOS, NO VEGF VEGF VEGF-receptor 2 Capillaries Perfusion (red cell velocity, flux) VEGF-receptor 2 Capillary proliferation initiated Capillary proliferation continued No change in C:F ratio Tissue hypoxia ? Increase in C:F ratio Fig. 1. Schematic representation of the time course of changes in microcirculatory haemodynamics, growth 11 Angiogenesis steps: Angiogenic stimuli drawing by Florence Wu 12 Review Angiogenesis steps: Angiogenic stimuli O2 FA O2 Glc Glc Glc PHD HIF FA-CoA Pyr Lac OXPHOS cardiomyocyte aerobic metabolism Lac ROS O2 Flk Glc PHD Pyr Lac O2 Glc H+-ATPase Glc H+ HIF Pyr OXPHOS resting EC aerobic glycolysis Fraisl, Mazzone, Schmidt, and Carmeliet. Dev Cell. 2009 ure 2. Endothelial Metabolism Correlates with the Abundance of Oxygen navigating EC anaerobic glycolysis 13 Computational model of angiogenic stimuli Reglin, Secomb, and Pries. Am J Physiol Soc Heart Circ Physiol. 2009 14 ing time of 4 seconds, by using a digital image analysis system.20 The spatial shift between each of the line pairs was 10 CRBC /ml automatically determined by means 10aml O2/ml 0.52 of cross-correlation ml O2 then P 38 30 ration xperimental setup,17 O2 50 procedure and converted into v,. Periodic Torr Torr 30 changes of flow hering and scanning velocity coupled to heart rate and breathing were eliminated n 3 30 5 3 hematocrit determi- RBC by averaging velocities over the complete30 cm3 O2recorded. orr 1 sequence cm T 3.38 10 1 . 5Male Wistar rats p3 O2 cAveraged vcl values 3determined by spatialcm3 O2 cm were orr 1 cm l 1 correlation 3 T m 3 Torr 1 5 10 33 e5 anesthetizedComputational methods:blood velocity (vb). 3 model 1 with 3 O2then converted 1 mean b0 cm 33 cm For cm 1 s cm 3 Torr into8.3 10 1 iophysical 2 single-file Torr 1 K 33 tion (0.1 mg/kg IM pl flow conditions, v,, can be assumed to be identical O mean cell to 10 3 1 1 1 cm cm s Torr sodium). During the O2velocity (vc). The relation between v, 33 vb, in turn, is and Dt Hemodynamics calculations to 2predict flow resistance:...
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This note was uploaded on 01/20/2014 for the course BME 410 taught by Professor Han during the Spring '08 term at USC.

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