<p>   </p> <p>Environmental toxicants such arsenic (As) and lead (Pb) are chemicals that enter the environment and can result in adverse health effects humans, especially during development. This dissertation work evaluated As and Pb to determine if developmental toxicity significantly changes at lethal and sub-lethal mixture concentrations using the zebrafish model. Joint action models were applied to survival data to determine the type of interaction. Metal exposures were from 1-120 hours post fertilization (hpf). As concentrations were 0-7,500 ppb. Pb concentrations were 0–100,000 ppb. The LC25, LC50, and LC75 values at 120 hpf from single metal exposures were used to select mixture concentrations for modeling. The survival data indicated an additive effect occurred at lethal concentrations. </p> <p>The impact of the mixture on behavior, morphology, and gene expression was then evaluated at sub-lethal concentrations of 10 and 100 ppb As and Pb individually or in mixtures. Data was analyzed with a repeated measures ANOVA (behavior) or an ANOVA (morphology and qPCR) with the least significant difference test (α=0.05). Zebrafish larvae exposed to 10 ppb As exhibited hyperactivity in all dark phases for the distance moved, time moving, and velocity, while those exposed to 10 ppb Pb only showed an increase in distance moved and velocity in the first dark phase. The 10 ppb mixture was found to have an intermediate impact with increased time moving in all dark phases and increased distance moved and velocity only in the first dark phase. In contrast, hyperactivity was observed only in the 100 ppb As and 100 ppb mixture treatment in the last two dark phases for time spent moving. No significant behavioral alterations occurred in the 100 ppb Pb treatment. A decrease in mean brain length and brain length ratio to the total length in the 10 ppb mixture was observed with no significant morphology changes observed for head length, head width, or total length. Alternatively, measurements of cerebral vasculature morphology in the mesencephalon (midbrain) and cerebellum (hindbrain) uncovered decreased total vascularization at 72 hpf (exposure 1-72 hpf) in both brain regions. This decrease occurred in all treatment groups in the mesencephalon and in all treatment groups, except the 100 ppb Pb and 10 ppb As treatment groups in the cerebellum. In addition, decreased sprouting and branching occurred in the mesencephalon, while only decreased branching was measured in the cerebellum. The 10 ppb Pb treatment group showed unique perturbations in several cerebral vasculature endpoints evaluated, which was also observed in a specific gene expression alteration pattern different from the other treatment groups. To identify molecular changes associated with these changes, expression of genes related to angiogenesis and vasculogenesis (i.e., <em>vegfaa, wnt7aa,</em> and<em> lrp1aa</em>) and genes associated with tight junctions (i.e., <em>cldn5a</em> and <em>cldn5b</em>) were assessed at 72 hpf. Increased <em>cldn5b</em> expression was detected in all treatment groups, while <em>cldn5a </em>was increased in only the 10 ppb Pb treatment group. In addition, <em>wnt7aa</em> was only decreased in the 10 ppb Pb treatment group. Alternatively, <em>vegfaa</em> was increased in the 100 ppb As and 100 ppb mixture treatment groups and no changes were detected for <em>lrp1aa</em>. In summary, cerebral vascular toxicity outcomes in the 10 ppb mixture treatment were primarily driven by changes in the 10 ppb Pb treatment group, while perturbations in the 100 ppb mixture treatment group aligned with the 100 ppb As alterations. In addition, the non-linear dose response for 10 and 100 ppb Pb treatment groups agree with observations in prior studies. qPCR results indicate that both metals together and separately alter cerebral vasculature development at environmental regulatory levels. </p> <p>Lastly, with the increase in the prevalence of neurodegenerative diseases increasing globally, there is a need to evaluate more therapeutics at a high through-put pace and to pinpoint the cause of the sporadic cases. CRISPR-Cas9 technology offers a relatively inexpensive, reliable, and precise advantages over its predecessors when it comes to producing mutant disease models of neurodegeneration. A method to create the expression vector needed for creation of a CRISPR Cas9 knock-in model is detailed in this dissertation. The methodology to insert a chimeric DNA sequence contain human DNA has been created, and the <em>in silico</em> assays used to produce the reactant for this methodology were successful. It has been determined that the efficiency of this knock-in method is limited to the success of producing the chimeric model which is limited itself by the number of molecules included into the chimeric sequence. Overall, the results show that the overlap primers designed in silico need to be re-designed to improve efficiency of the initial reactions required to produce the first plasmid containing the required machinery for a successful knock in of exogenous human DNA.</p>

Indiana University-Purdue University Indianapolis (IUPUI) / Although paclitaxel is a commonly used anti-neoplastic agent for the treatment of solid tumors, therapy often results in a number of side effects, the most debilitating of which is peripheral neuropathy. Peripheral neuropathy is defined as a pathology of peripheral nerves, and, depending on the type of nerves damaged, the neuropathy can be classified as sensory, motor, or autonomic neuropathy. In the case of peripheral neuropathy induced by paclitaxel, the symptoms are experienced in the extremities and are sensory in nature. Patients undergoing chemotherapy with paclitaxel often report sensory disturbances such as burning, tingling, numbness, a diminished sensation to pain and temperature, loss of vibration sense, loss of proprioception, and loss of deep tendon reflexes. Electrophysiological abnormalities including decreased sensory nerve action potential amplitude and conduction confirm damage to large myelinated fibers. However, the involvement of damage to small diameter sensory neurons in the etiology of paclitaxel – induced peripheral neuropathy is still controversial. Therefore, experiments were performed to determine if paclitaxel alters the function of small diameter sensory neurons and to examine the mechanisms responsible for the change in function. vi Sensory neuron mediated vasodilatation in paclitaxel – injected animals was examined as an indirect measure of calcitonin gene related peptide (CGRP) release and therefore of sensory neuron function. CGRP release was also directly measured from central terminals in the spinal cord. To examine mechanisms of paclitaxel – induced sensory neuron damage, CGRP release and neurite length was examined in paclitaxel – treated sensory neurons in culture. The results demonstrate that (1) paclitaxel decreases the ability of small diameter sensory neurons to produce an increase in blood flow in the skin; (2) paclitaxel alters the release of CGRP from the small diameter sensory neurons; (3) paclitaxel causes the neuronal processes of isolated sensory neurons to degenerate. This dissertation provides novel information showing that paclitaxel alters the function of small diameter sensory neurons and thus provides a better understanding of the mechanisms mediating the sensory disturbances characteristic of peripheral neuropathy resulting from chemotherapy with paclitaxel.

The retina is one of the most metabolically active tissues in the body and the high energetic demand is met by a well-organized vascular network. Aberrant vasculature is a prominent feature of many vision-threatening diseases, and although angiogenic pathways have been extensively studied the limited efficacy of therapies currently available for the treatment of these diseases suggests that there is more to be elucidated. The caspase family of proteases is best known for their roles in programmed cell death and inflammation, however members of this family have been found to have essential functions independent of cell death. Caspase-8, in particular, has been previously shown to be essential for embryonic vascular development, however, a requirement for caspase-8 in postnatal vascular development has not been established and it is unclear how caspase-8 exerts its function. In this study, we investigate the cell specific roles of caspase-8 in the development of the retinal vasculature using the postnatal mouse retina as our model and identified endothelial caspase-8 as a mediator of canonical Wnt signaling. Inducible endothelial cell-specific caspase-8 knockout (Casp8 iECKO) resulted in a delay in early angiogenesis and barrier establishment, and an increase in inflammation and premature vascular remodeling compared to littermate controls. Assessment of Lef1, a downstream effector of the Wnt pathway, confirmed that this phenotype was a result of inhibited Wnt signaling. We additionally show that caspase-8 mediates this pathway through degradation of its substrate HDAC7. HDAC7 has been shown previously to bind to β-catenin blocking its nuclear translocation. Caspase-8 mediated HDAC7 degradation restores β-catenin translocation and downstream Wnt signaling. We also explore the function of caspase-8 in myeloid cells – microglia and macrophages – during angiogenesis. We used an inducible myeloid-specific caspase-8 knockout (Casp8 imGKO) mouse and found that loss of caspase-8 in these cells did not affect angiogenesis. However, Casp8 imGKO resulted in a reduction in microglia number and a change in their morphology specifying a role for caspase-8 in mediating cell survival and activation in microglia. Altogether we show that caspase-8 exerts cell specific functions during retinal angiogenesis that are independent of cell death. We elucidate a novel role of caspase-8 in mediating Wnt/β-catenin signaling, and implicate caspase-8 as a potential therapeutic target in pathological angiogenesis.

Tissue Engineering A Blood Vessel Mimic While Monitoring Contamination Through Sterility Assurance Testing Navid Djassemi Tissue engineering blood vessel mimics has been proposed as a method to analyze the endothelial cell response to intravascular devices that are used in today’s clinical settings for the treatment of cardiovascular disease. Thus, the development of in vitro blood vessel mimics (BVMs) in Cal Poly’s Tissue Engineering Lab has introduced the possibility of assessing the characteristics of cellular response to past, present, and future intravascular devices that aim at treating coronary artery disease. This thesis aimed at improving the methods and procedures utilized in the BVM model. Initial aspects of this project focused on using an expanded polytetrafluoroethylene (ePTFE) scaffold in conjunction with human endothelial cells to replicate the innermost intimal layer of a blood vessel. Human umbilical vein endothelial cells (HUVECs) were pressure sodded onto ePTFE scaffolds through cell sodding techniques in an attempt to effectively and consistently replicate and assess the intimal layer. Through each study ePTFE grafts were subjected to different culture times and steady flow rates to observe and compare the differences in the endothelial cell deposition. Results were inconsistent, although moderate cell adhesion was noted throughout each of the BVM setups. Each study exhibited a range of cell sodding density rates. In the second phase of the thesis, contamination assessment protocols were implemented in the BVM lab. The intent of this part of the project was to assess the relative sterility in the cell culture lab, a critical component involved with the success or hindrance of cell and tissue cultures. Using microbiological validated methods, microbiological tests were conducted to examine the levels of microbial growth in and around the tissue engineering lab. Results were tracked over a two month period in the lab with several observations of aerobic microorganism growth on various counter and lab surfaces. Higher growth trends were found on surfaces outside the cell culture lab, in the general TE lab area. These findings were used to provide overall suggestions on tracking microbes for long-term durations in ongoing BVM setups to directly improve the overall sterility assurance of the studies. As the project reached its conclusion a look back at all the BVM setups and contamination assessments lead to a few suggestions for improving aseptic techniques within the TE lab, such as monitoring microbial growth in the culture processes, creating limit specifications, and creating a standardized way to regulate quality control within the lab environment. Furthermore, as the development BVM evolves, the findings from this report can be used with related research for improving the culture conditions of various BVM studies.

Colonoscopy is essential for colorectal cancer screening and disease surveillance. It can remove pre-cancerous colon polyps to reduce a patient’s cancer risk. This thesis aims to improve colonoscopy’s localization using motion tracking and colonoscopy’s coverage using surface mapping. Chapter 4 describes an endoscope motion tracker that records the scope’s insertion length, rotation, and speed during a colonoscopy. The endoscope tracker’s motion record can be combined with the endoscope’s video to localize colon polyps or cancers. In the future, the device could record highly skilled manoeuvres performed by endoscopists to help train medical residents. It is difficult to image the colon’s mucosa because the colonoscope’s camera has a limited field of view. Chapter 3 uses a 180° fisheye camera to unwrap high resolution panoramas of a colon phantom. The panoramas are then combined into a mosaic map of the colon phantom’s surface. The colon’s surface is approximated as a cylinder. Follow up experiments could test our mapping algorithm using imagery from a wide-angle, high-definition colonoscope. Chapter 2 describes another technique to localize locations where polyps have been removed—blood vessel landmarks. Colonic blood vessels from a pig were imaged to determine if they could be used to fingerprint locations on the colon’s wall. Blood vessels are also useful image features for surface mapping. The proof-of-concept experiments successfully imaged large arteries but further work is needed to image the small capillaries in the colonic mucosa and to image the veins. In summary, we have visualized colonic blood vessels to test if they could be useful landmarks, tested using an extended field of view camera to create an unwrapped map of the colon wall, and designed an endoscope tracker to help localize abnormal tissue. Combining the endoscope tracker with the other two techniques should make is possible to accurately map the colon. / Thesis / Doctor of Philosophy (PhD) / Colonoscopy is a powerful tool for colon cancer screening. A colonoscopy can decrease the chance of developing advanced cancers by removing pre-cancerous polyps before they grow. This research works to improve colonoscopy’s localization using motion tracking and its coverage using surface mapping. We have developed an endoscope motion tracker that records the scope’s insertion length, rotation, and speed during a colonoscopy. It is In described in Chapter 4. The recorded motion can be combined with the endoscope’s video to improve colon cancer localization. Next, it is difficult to image the colon’s mucosa because the colonoscope’s camera has a limited field of view. Chapter 3 uses a 180° fisheye camera to unwrap high resolution panoramas of a colon phantom. The panoramas are then combined into a cylindrical surface map. Finally, Chapter 2 images the colon’s blood vessels to determine if they can fingerprint locations on the colon’s wall.

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近年来，血管类疾病已经成为人类健康的第一杀手。每年有成百上千万人死于血管疾病。血管介入术是一种非常有前景的血管类疾病的治疗手段。血管介入术是一种微创手术，它已经被广泛的用于治疗中风，血管狭窄，血管瘤等疾病。相对于传统的开放式手术，它具有风险低，恢复快，住院时间短等优点。该疗法通常在透视影像的引导下由导管和导线在血管内协同完成手术过程。因为介入术的复杂性和特殊性，作为介入手术医生的必要技能，掌握手术中手眼协同，各种手术器具的使用和复杂细致的手术流程无疑是一个巨大的挑战。因此，迫切地需要一种高效、安全的训练系统。相对于传统的训练方法，基于虚拟现实技术的训练系统是一种非常好的训练手段。 / 为了建立一套高仿真的介入手术训练模拟器，首先，我们要为病人的血管网重建三维模型。我们提出了一种自动的提取中心线的方法，用来从分割好的CTA/MRA体数据中获取病人血管网的中心线。基于改进的平行传递算法，沿着这些中心线，生成了一系列连续的标架。根据这些标架，我们构造了血管的横截面，并在此基础上生成了光滑连续的三维血管模型。 / 其次，作为血管介入术中最基础和最重要的手术器械，我们为导管和导线建立了物理模型。我们提出了一种基于最小势能原理的可变形的模型用于模拟导管和导线对于受力的反应。我们还提出了一个快速并且稳定的多网格算法来保证模拟的真实性和严格的实时交互要求。另外，我们做了几组实验。通过这些实验，验证了多网格算法在稳定性、实时性、模拟的真实性等方面满足了我们对于训练用模拟系统的要求。 / 再次，为了模拟血管栓塞术的手术过程，我们提出了一种模拟线圈填充血管瘤的过程的新方法。通过加总线圈弯曲变形的弹性势能、血管瘤变形的弹性势能以及外力做的功，我们建立了在血管栓塞术的环境下的总势能模型。为了求解这个模型，我们提出了一个基于有限元方法的求解器。从而模拟了线圈在介入医生的操作下慢慢的进入血管瘤，并缠绕起来的过程。 / 另外，我们提出了一个分层圆柱网格模型（LCGM）用于模拟在血管网中血流的运动。这一模型在几何上和拓扑结构上都非常适合我们的应用。我们将血液在血管中的流动近似为一维的层流，并用一组线性等式描述了血管网中流速与血压的关系。通过求解这一线性系统，得到了在分层圆柱网格模型下血流的速度场。依据这个血流的速度场，我们采用平流-扩散模型来模拟造影剂在血管中的传播的过程。 / Vascular diseases have been becoming the number one cause of death worldwide in recent years. Millions of people were killed by vascular diseases each year. An increasingly promising therapy for treating vascular diseases is Vascular Interventional Radiology (VIR). VIR is a minimally invasive surgery (MIS) procedure, which has been widely used to cure stroke, angiostenosis, aneurysm and etc. A low risk, an accelerated recovery and a shorter stay in hospital are important advantages over the traditional vascular surgery. This therapy is performed by a guidewire-catheter combination inside the blood vessels under the guidance of the fluoroscopic imaging. Because of the complexity and particularity of these procedures, it is a great challenge to master hand-eye coordination, instrument manipulation and procedure protocols for each radiologist mandatory. An efficient and safe training system is needed urgently. In contrast to these traditional training methods, virtual reality (VR) based simulation systems is a pretty good surrogate. / In order to build a high fidelity interventional simulator for physician training, firstly, we reconstructed the three dimensional (3D) model for the vascular network of the patients. An method of automatic skeleton extraction was proposed to acquire the centerline of the vascular network from the segmented volume data from CTA/MRA. A series of continuing frames were generated along with the centerline based on improved parallel transporting method. According to these frames we built the crossections of the vessels and further the 3D vascular model with the smooth meshes. / Secondly, as the most basic and important instruments in the VIR procedure, the catheter and guidewire were modeled and simulated physically. We developed a deformable model to simulate complicated behaviors of guidewires and catheters based on the principle of minimum total potential energy. A fast and stable multigrid solver was proposed to ensure both realistic simulation and real time interaction. A series of experiments were conducted to evaluate our multigrid solver in terms of stability, time performance, the capability of simulating catheter behaviors and the realism of catheter deformation. / Thirdly, to simulate the procedure of embolization, we proposed a novel method to simulate the motion of coil and their interactions with the aneurysm. We formulated the total potential energy in the embolization circumstance by summing up the elastic energy deriving from the bending of coils, the potential energy due to the deformation of the aneurysm and the work by the external forces. A novel FEM-based approach was proposed to simulate the deformation of coils. And the motion of coils and their responses to every input from the interventional radiologist can be calculated globally. / Fourthly, we proposed our Layered Cylindrical Gird Model (LCGM) for simulating blood flow in vascular network, which is pretty suitable for sampling the vascular network geometrically and topologically. The blood flow in vessels was regarded as 1D laminar flow and formulated into a set of linear equations based on the Poiseuille law to describe the relationship between the speed of flow and the pressure. Solving those equations, we got the velocity fields in the blood flow. In terms of the velocity fields, an advection-diffusion model was adopted to simulate the propagation of contrast agent with the blood flow. / Finally, all above techniques and procedures were implemented and integrated into a simulation system for training the medical students to acquire the endovascular skill, and an empirical study was also designed based on a typical selective catheteriza- tion procedure to assess the feasibility and effectiveness of the proposed system. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / 最后，我们将所有以上提到的技术和方法集成到模拟系统中用于训练医学院的学生，并使他们获得血管介入术的技能。并且，我们基于一个典型的导管插入术过程，使用经验分析的方法对模拟系统的可用性和效率进行了评估。 / Li, Shun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 105-116). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in also Chinese. / Abstract --- p.i / Acknowledgement --- p.vi / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Vascular Modeling --- p.14 / Chapter 2.1 --- Introduction and Related Work --- p.14 / Chapter 2.2 --- Vascular Skeleton Graph Construction --- p.15 / Chapter 2.2.1 --- Chamfer distance transform and Dijkstra's shortest-path algorithm --- p.17 / Chapter 2.2.2 --- End vertices retrieval --- p.19 / Chapter 2.2.3 --- The algorithm of vascular skeleton extraction --- p.21 / Chapter 2.3 --- Vascular Modeling --- p.21 / Chapter 2.3.1 --- Tubular Model --- p.21 / Chapter 2.3.2 --- Bifurcation Model --- p.23 / Chapter 3 --- Catheter Simulation --- p.28 / Chapter 3.1 --- Introduction and Related Works --- p.28 / Chapter 3.2 --- Catheter Simulation --- p.31 / Chapter 3.2.1 --- Kirchhoff Theory of Elastic Rod --- p.32 / Chapter 3.2.2 --- Problem Formulation --- p.34 / Chapter 3.2.3 --- The Multigrid Iterative Solver --- p.38 / Chapter 3.3 --- Collision detection --- p.45 / Chapter 3.4 --- Validation of the Catheter Simulation Method --- p.47 / Chapter 3.4.1 --- Stability --- p.49 / Chapter 3.4.2 --- Time Performance --- p.50 / Chapter 3.4.3 --- Preservation of Curved Tip --- p.51 / Chapter 3.4.4 --- The realism of catheter deformation --- p.53 / Chapter 4 --- Coil Embolization Simulation --- p.59 / Chapter 4.1 --- Introduction and Related Work --- p.59 / Chapter 4.2 --- Methodology --- p.61 / Chapter 4.2.1 --- Total potential energy of a coil --- p.61 / Chapter 4.2.2 --- The FEM-based numeric solver for interactive coil simulation --- p.61 / Chapter 5 --- Angiography Simulation --- p.70 / Chapter 5.1 --- Introduction and related works --- p.70 / Chapter 5.2 --- The Equations of Fluid --- p.72 / Chapter 5.3 --- Layered Cylindrical Gird Model --- p.73 / Chapter 5.4 --- Numerical Method --- p.76 / Chapter 5.4.1 --- Evaluation of the velocity field of blood flow --- p.76 / Chapter 5.4.2 --- Evaluation of the density field --- p.78 / Chapter 5.5 --- Results --- p.81 / Chapter 6 --- System Implementation and Evaluation --- p.84 / Chapter 6.1 --- Introduction and Related Work --- p.84 / Chapter 6.2 --- System Construction --- p.85 / Chapter 6.3 --- Empirical Study of the Training System --- p.89 / Chapter 7 --- Conclusion and Discussion --- p.98 / Chapter 7.1 --- Geometric Modeling of Vasculature --- p.99 / Chapter 7.2 --- Catheterization Simulation --- p.99 / Chapter 7.3 --- Embolization Simulation --- p.100 / Chapter 7.4 --- Angiography Simulation --- p.101 / Chapter 7.5 --- System and Evaluation --- p.102 / Publication List --- p.103 / Bibliography --- p.105

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, Durban, South Africa, 2015. / Background: When a soft tissue injury occurs the blood vessels and surrounding tissue are damaged leading to haemorrhaging and inflammation. Cryotherapy (cold therapy) is generally acknowledged as the preferable treatment by manual therapists during this immediate post-traumatic period of an injury. Cryotherapy has been shown to result in vasoconstriction decreasing the rate of blood flow which has a favourable effect on inflammation and pain. The commercially available cooling cuff is a relatively new cryotherapy modality offering a mechanism of cooling that does not require freezing and is easy to use. The polymer granules within the cooling cuff are activated by emersion in water therefore freezing is not required making the cooling cuff readily available compared to more traditional forms of cryotherapy. Aim: The aim of this study was to determine the effect of a moist ice pack and a commercially available cooling cuff radial artery blood flow (cm.s-1) and radial artery lumen diameter (mm) after 15 minutes of application. Method: This study was a pre-test post-test design utilising 43 asymptomatic participants that were randomly allocated to one of two groups. Each group either received a standard moist ice pack or a commercially available cooling cuff, placed on the ventral surface of the participants forearm, over the radial artery, for a duration of 15 minutes. Measurements were taken with a Doppler ultrasound to determine radial artery blood flow and lumen diameter, prior to the intervention and 15 minutes after the cryotherapy application. Data analysis was performed using IBM SPSS VERSION 20 (IBM Corp. Released 2010.IBM SPSS Statistics for Windows, Version 19.0. Armonk, New York: IBM Corp.). Statistical significance was set at a p< 0.05 level. Intra-group and inter-group comparisons were measured using repeated measures ANOVA testing. Results: Both the moist ice pack and commercially available cooling cuff resulted in a significant decrease in radial artery blood flow (p< 0.001) after 15 minutes of application with no significant changes being observed in radial artery diameter Conclusions: The commercially available cooling cuff resulted in a similar effect on radial artery blood flow and lumen diameter as moist ice, indicating that the commercially available cooling cuff may be utilised in the acute phase of an injury to alter blood flow. / M

Neste estudo avaliou-se a ação da Angiotensina II (Ang II) e do bloqueio dos seus receptores AT1 e AT2 no remodelamento da matriz extracelular (MEC) e traçamos o perfil da sinalização intracelular envolvida no processo. O estudo foi feito in vivo em camundongos isogênicos C57Bl/6J submetidos a tratamento durante 7 e 14 dias com doses subpressoras de Ang II, bloqueador do receptor AT1 (Losartan) e uma combinação destes. Os animais foram sacrificados e procedeu-se a coleta de tecidos de artérias (aorta, carótida e femoral), coração, rins e pulmão para análise da síntese e degradação de componentes da MEC. Foram feitas avaliações hemodinâmicas, morfológicas em microscopia de luz, morfométricas, imunohistoquímicas para os componentes da matriz extracelular: colágeno (tipos I, III, IV e VI), fibronectina, tenascina-C, elastina, metaloproteinases (tipos 2 e 9), e quantificação de algumas proteínas ligadas à sinalização intracelular da via das Proteínas quinases ativadas por mitógenos (MAPK - Mitogen-activated protein kinases) usando-se Western Blotting. / In this study we evaluated the action of Angiotensin II (Ang II) and the blockade of AT1 and AT2 receptors in the remodeling of extracellular matrix (ECM) and outlines the process involved in intracellular signaling. The study was done in vivo in C57Bl/6J inbred mice undergoing treatment for 7 and 14 days subpressor doses of Ang II, AT1 receptor blocker (Losartan) and a combination thereof. The animals were sacrificed and proceeded to collect tissues of arteries (aorta, carotid and femoral arteries), heart, kidneys and lungs for analysis of the synthesis and degradation of ECM components. We assessed hemodynamic, morphological light microscopy, morphometry, immunohistochemistry for extracellular matrix components: collagen (types I, III, IV and VI), fibronectin, tenascin-C, elastin, metalloproteinases (types 2 and 9) and quantification of some proteins related to intracellular signaling pathways of the mitogen-activated protein kinase (MAPK) using Western Blotting.