One critical barrier to the success of vascular tissue engineering strategies is the need for appropriate endothelial cell sources. Adult stem and progenitor cells have emerged as a potentially promising cell source but very little is known about their functional potential. The endothelial cell (EC) resides on the vascular wall at the interface with flowing blood and is a key mediator of hemostasis and thrombosis. These studies investigated the use of endothelial progenitor cells (EPCs) derived from peripheral blood as a vascular lining on an engineered blood vessel substitute. Models were developed to investigate two aspects of the vascular environment, shear stress and substrate on EPC response at the gene, protein and functional levels. Isolation of EPC colonies from peripheral blood gave rise to cells which displayed an endothelial-like phenotype with expression of many EC specific markers and functions. Through the use of transcriptional profiling, results demonstrated that EPC gene expression was generally less sensitive to shear stress than ECs but shear stress preconditioning did result in upregulation of the EPC antioxidant defense system and promoted anticoagulant function. When co-cultured on a model of the vascular wall, EPCs altered their gene expression and favored a response more similar to mature vascular ECs. In a baboon arteriovenous shunt, shear stress preconditioned EPCs were able to resist platelet deposition and provided a non-thrombogenic lining on an engineered blood vessel substitute. Although significantly more research needs to be done, this work has provided an understanding of EPC function in the shear stress environment and provides evidence that EPCs are a viable endothelial cell source for vascular tissue engineering.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

An Investigation was undertaken to determine the effects of beta-hydroxy thujaplicin and gamma-thujaplicin, used as the sodium salts, on blood pressure and heart rate in the rat. Attempts were made to discover the sites and modes of action of these two compounds. Gamma-thujaplicin 30mg/kg. produced either a vasopressor or a vasodepressor response in anesthetized rats. The pressor response was usually more pronounced, than the vasodepressor response. Tachycardia occurred with either blood pressure response. To determine whether the central nervous system was necessary for the vasopressor and tachycardiac response, pithed rats were used. In these preparations gamma-thujaplicin produced only a fall in blood pressure and a decrease in heart rate. The effect of adrenergic blocking drugs on the response to gamma-thujaplicin was investigated. In the anesthetized rat the vasopressor response was reduced significantly by both phenoxybenzamine and pronethalol; however, the heart rate was unaffected. In the pithed rat the vasodepressor response produced by gamma-thujaplicin was not affected by pronethalol; however, gamma-thujaplicin produced a significantly greater decrease in heart rate after treatment with pronethalol. To determine whether gamma-thujaplicin had adrenergic alpha-receptor or beta-receptor blocking properties its effect on blood pressure responses to noradrenaline and isoproterenol was investigated. Gamma-thujaplicin was found to reduce the vasopressor effect of intravenous noradrenaline 0.5ug/kg. but had no effect on the vasopressor response produced by isoproterenol 0.25ug/kg. The pressor response to intravenous physostigmine salicylate 40ug/kg. was unaffected by gamma-thujaplicin. The increase in heart rate and blood pressure produced by gamma-thujaplicin, with injections repeated every fifteen minutes, was greatly reduced after the second dose. It is concluded that in the anesthetized rats the vasopressor and tachycardiac response produced by gamma-thujaplicin were of central origin while the vasodepressor effect was a result of direct action on vascular smooth muscle. The vasopressor response could involve the stimulation, via sympathetic nerves, of alpha-adrenergic receptors of vascular smooth muscle. Gamma-thujaplicin can produce alpha-adrenergic receptor, blockade to exogenous noradrenaline, but not to endogenously released noradrenaline since the response to intravenous physostigmine was not affected by the tropolone. Beta-hydroxy thujaplicin 10mg/kg. caused a vasopressor response in all anesthetized and pithed rats tested. The vasopressor response was abolished by phenoxybenzamine in both anesthetized and pithed rats. Beta-hydroxy thujaplicin did not alter isoproterenol induced tachycardia or the vasopressor response produced by physostigmine salicylate. It is concluded that beta-hydroxy thujaplicin caused its vasopressor effect in rats by acting directly on the alpha-adrenergic receptors of vascular smooth muscle. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

The sympathetic nervous system is crucial for controlling multiple cardiac functions and its overactivity is associated with many cardiovascular diseases (CVD). Chronic intermittent hypoxia (CIH) is a current model for sleep apnea, which constitutes a major risk factor for CVD through sympathetic overactivity. However, a comprehensive neuroanatomical map of the sympathetic innervation of the heart is unavailable which impedes our understanding of the remodeling of this map in pathological conditions. First, we used a combination of state-of-the-art techniques, including flat-mount tissue processing, immunohistochemistry for tyrosine hydroxylase (TH, a sympathetic marker), confocal microscopy and Neurolucida 360 software to trace, digitize, and quantitatively map the topographical sympathetic innervation in the whole heart of mice. Then we integrated our tracing data onto a 3D heart scaffold. Second, we determined the remodeling of sympathetic innervation in CIH, by exposing mice to either room air or CIH for 8-10 weeks. We found that (1) 4–5 extrinsic TH-IR nerve bundles entered the right atrium from the superior vena cava and the left atrium from the left precaval vein. Although these bundles projected to different areas of the atria, their projection fields partially overlapped. (2) TH-IR axon and terminal density varied considerably between different sites of the heart with the greatest density of innervation near the sinoatrial node region (P < 0.05, n = 6). (3) TH-IR axons also innervated blood vessels and adipocytes. (4) In ventricles: TH-IR axons formed dense terminal networks in the epicardium, myocardium, and vasculature. (5) TH-IR axons were traced and integrated into 3D heart scaffolds. (6) CIH significantly increased TH-IR innervation and complexity in the heart. Collectively, this work provided detailed mapping of catecholaminergic axons and terminal structures in the whole heart at single-cell/axon/varicosity scale in normal and CIH conditions. This work may provide a foundation for the functional study of sympathetic control of the heart and valuable neuromodulation strategies to treat CVD.

Cardiovascular disease remains one of the leading causes of mortality globally. Innovative techniques are required to tackle its anticipated rise due to rising obesity, diabetes and an ageing population. Personalised electronic coaching (eb coaching) using the Internet and emails may help motivate healthier living and be of clinical benefit in complementing current programmes for cardiovascular risk reduction. I investigated whether personalised ebcoaching on top of SOC was more clinically effective than SOC alone, in reducing cardiovascular risk in asymptomatic individuals with high cardiovascular risk. I lead a randomised controlled trial of 402 participants using robust surrogate markers to identify change over 6 months. I assessed the feasibility of using cardiovascular magnetic resonance surrogate markers to guide their use in future studies of lifestyle interventions. I performed systematic reviews to identify 1) similarities and differences among leading primary prevention guidelines that address cardiovascular screening and risk assessment and 2) guideline recommendations on lifestyle advice and interventions to identify how ebcoaching could be used and what advice to incorporate in ebcoaching platforms. I found modest but statistically significant improvements in both ebcoaching and SOC groups to a similar level. Personalised ebcoaching did not show additional benefit in a highbrisk primary prevention cohort. It is feasible to use cardiovascular surrogate markers derived from cardiovascular magnetic resonance in lifestyle interventions studies. However, further studies correlating change in these markers with longbterm outcomes are required. Considerable discrepancies exist in the guidelines on risk on cardiovascular screening and risk assessment, with no consensus on optimum screening strategies or classification of high risk thus affecting treatment threshold. Guidelines did highlight the importance of lifestyle interventions in primary prevention and generally provided similar advice. Ebcoaching should not be incorporated into current prevention programmes for high risk populations unless the tools are improved and effectiveness is proven.

Thesis (M.P.H.)--University of Hong Kong, 2007.

Made available in DSpace on 2014-06-11T19:25:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T20:53:03Z : No. of bitstreams: 1 morais_mgt_me_botfm.pdf: 1390196 bytes, checksum: 479c99fbe7320445854c3f31cf0ad4ee (MD5) / Universidade Estadual Paulista (UNESP) / Apresentamos nesta dissertação, uma revisão dos estudos epidemiológicos e econômicos mostrando a doença cardiovascular como a grande pandemia do século XXI, tanto dos países desenvolvidos como naqueles em desenvolvimento. Colocamos em foco a necessidade de estudar-se a epidemiologia cardiovascular, que consiste na busca das causas de mudança da condição de saúde ou doença, nos seus fatores de risco e nos esforços para a preservação da saúde. Além das perspectivas epidemiológicas, há de se comentar as econômicas e sociais que seguem as primeiras uma vez que pessoas cada vez mais jovens adoecem causando um déficit na população economicamente ativa. Hoje a doença cardiovascular consome muitos recursos, saber quanto custa ao serviço público, com dados claros e fidedignos é a única forma de evitar um caos nos sistemas de saúde de todo o mundo. A grande maioria dos dados disponíveis hoje necessita de aperfeiçoamento para serem utilizados com êxito. No Brasil a criação do Sistema Único de Saúde SUS em 1988 norteada com os princípios da universalidade e da equidade, juntamente com os avanços tecnológicos e escassez de recursos, exige uma otimização dos recursos disponíveis sem, entretanto alterar a qualidade da assistência á saúde. Quando analisamos os gastos do SUS em saúde, observamos um incremento anual crescente, especialmente quando falamos das doenças cardiovasculares. Em 2007 foram registradas 1.157.509 internações por DCV no Sistema Único de Saúde (SUS) que custaram aos cofres públicos R$ 1.468.441.279,46. Em novembro de 2009 ocorreram 91.970 internações por DCV, resultando em um custo de R$ 165.461.644,33 (DATASUS). Os gastos continuam aumentando ano após ano de forma desastrosa. Sendo assim caracterizamos o gasto com as DCV especificamente... / We presented in this dissertation, a review of epidemiologic and economic studies showing the cardiovascular disease as the great pandemic of the XXI century much of the developed countries as in developing countries. We focuses the need to study the cardiovascular epidemiology, which consists in finding the causes of change in health condition or disease, in its risk factors and efforts to preserve health. Apart from the epidemiological perspective, we should also comment on the economic and social that follows the first since more and more young people become ill, causing a deficit in the economically active population. Today, cardiovascular disease consumes too many resources, how much it costs to public service, with clear and reliable data is the only way to avoid chaos in health systems around the world. The vast majority of data available today need improvement to be used successfully. In Brazil, the creation of the Sistema Único de Saúde in 1988 SUS guided with the principles of universality and equity, along with technological advances and dwindling resources, requires an optimization of available resources without however changing the quality of healthcare. When we analyze SUS expenses on health, we observe a growing annual increase, especially when it comes to cardiovascular diseases. In 2007 we registered 1,157,509 admissions for CVD in the Sistema Único de Saúde (SUS) that cost the public treasury R$ 1,468,441,279.46. In November 2009 there were 91,970 admissions for CVD, resulting in a cost of R$ 165,461,644.33 (DATASUS). Expenses continue to increase year after year in a disastrous way. Therefore we characterize the CVD expenses specifically heart disease by the government through a retrospective study, with descriptive purpose, developed within the specialty of cardiology where numerical data... (Complete abstract click electronic access below)

Cardiovascular disease is a worldwide problem for both men and women and accounts for nearly 17.9 million deaths every year. Cardiovascular disease affects men and women differently and has resulted in more deaths in women since the 1980’s. Estrogen status decreases with age and as women go through menopause, it increases the burden of CVD events. Clinical studies have shown that estrogen can have cardioprotective effects via its receptors. These receptors binding causes pleotropic affects in signaling to maintain cardiovascular homeostasis. There are limited studies on estrogen loss in the aging heart over a continuous span. We therefore examined the effects of estrogen loss and its role in cardiac structure and function over time in female mice. This research was a collaborative project by 25 undergraduate students. Studies have shown undergraduate research to be extremely useful in improving undergraduate students’ analytical, communication, statistical knowledge, and other scientific and laboratory skills (Tan et al., 2022). During this lab, students performed various histological staining methods, analysis of echocardiograms, and animal research. Female mice were ovariectomized at 2.5 months of age or underwent a SHAM (mock) surgery. Echocardiography was preformed to examine the cardiac structure and function at 1, 3, 5, 12, and 18 months post ovariectomy. Hearts were removed at each time point and sectioned at 4µm thick. Cardiac hypotrophy was then assessed by histological staining using Wheat Germ Agglutin and myocyte cross-sectional area was measured of the stained images. There was a significant increase in cardiac hypertrophy in the 1-month versus 18-month SHAM and OVX groups. Also, there was a significant increase in cardiac hypertrophy between the SHAM and OVX groups at 1-month, 3-month, and 5-month OVX. Echocardiography results revealed significant increases in the diastolic (DD) and systolic diameter (SD) for the SHAM and OVX group at 1-month versus 18-month. Percent Fractional (%FS), and Ejection Fraction (EF) were significantly higher in the OVX group versus SHAM at 1, 5, and 18-month time points. This work highlights the impact of prolonged estrogen loss on changes in cardiac structure and function in the aging female heart.

Thesis--University of Mississippi. / Vita. Photocopy of typescript. Ann Arbor, Mich.: University Microfilms International, 1977. -- 21 cm. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 138-146).

The introduction of antiretroviral drugs has dramatically increased the lifespan of human immunodeficiency virus (HIV)-infected patients, shifting the major concern towards long-term morbidity and mortality, particularly an increased risk of cardiovascular complications. Antiretroviral therapy has been proposed to be one of the contributing factors. However, existing evidence for the role of antiretroviral therapy in the development of cardiovascular diseases is controversial. Therefore, in the present thesis, the effects of several antiretroviral drugs on the vascular system were investigated. In view of the contribution of vascular inflammation in the development of cardiovascular diseases, the first study examined the effects of acute treatment of efavirenz, indinavir, saquinavir, lopinavir and ritonavir on the release of major inflammatory markers, interleukin (IL)-8, soluble intercellular adhesion molecule 1 (ICAM-1) and monocyte adhesion molecule 1 (MCP-1) in human umbilical vein endothelial cells in the absence or presence of lipopolysaccharide, a pro-inflammatory stimulus. The results demonstrated that efavirenz and the combination of lopinavir and ritonavir, at concentrations present in human plasma, reduced the IL-8 release, but not that of soluble ICAM-1 and MCP-1 in endothelial cells exposed to lipopolysaccharide. The data, therefore, suggest that efavirenz and lopinavir plus ritonavir may possibly have anti-inflammatory effects. Since these findings seems to contradict with the increased incidence of cardiovascular diseases associated with antiretroviral therapy, in vivo experiments were performed to further characterized the effects of antiretroviral drugs on the cardiovascular system. In the second study, the atherogenic effects of long-term treatment (eight weeks) with efavirenz, abacavir and lamivudine, alone or in combination (as used clinically), were investigated in apolipoprotein E deficient (Apo-E-/-) mice (hyperlipidemic/atherosclerotic model) and the corresponding wild-type mice of both genders. All drug treatments had no effects on the lipid profile, nitrotyrosine expression in the liver (an indication of oxidative stress) and the degree of atherosclerotic lesions in all mice. Efavirenz and lamivudine did not have any significant effects on acetylcholine- and sodium nitroprusside-induced relaxations in all mice. Abacavir and the combination of the three drugs did not have any effects on acetylcholine-induced relaxation in aortae of wild-type mice, but impaired acetylcholine-induced relaxation in those of male Apo-E-/- mice without affecting sodium nitroprusside-induced relaxation. The reduction in relaxation was likely mediated by the cyclooxygenase pathway since indomethacin restored the reduction in relaxation. In male Apo-E-/- mice, IL-6 levels were increased by abacavir and the combined treatment, whereas serum amyloid P component (SAP) levels remained unchanged. Although no differences in the development of atherosclerotic lesions were observed, female Apo-E-/- mice receiving abacavir had better lipid profiles, no impairment in acetylcholine-induced relaxation and decreased serum IL-6 and SAP levels compared to male Apo-E-/- mice, revealing a vasculoprotective role of the female gender. In conclusion, the data suggest that certain, but not all, antiretroviral drugs may increase the risk of cardiovascular diseases, and that this risk may be exacerbated in hyperlipidemia but reduced in females. Antiretroviral drugs should be cautiously prescribed to HIV-infected patients to minimize cardiovascular adverse effects. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Philosophy