Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1959. / Includes bibliographical references (p. 94-96).

Thesis (Ph.D.) - University of Queensland, 2003. / Includes bibliography.

Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Rijksuniversiteit Limburg, Maastricht. / Met bibliogr., index, lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Orientador: Beatriz B. Matsubara / Resumo: Placa de aterosclerose em aorta torácica é uma importante causa de acidente vascular cerebral (AVC) e ataque isquêmico transitório (AIT). Sua gênese estaria relacionada com migração, para a circulação cerebral, de trombos e cristais de colesterol que se desprenderiam de placas complexas, localizadas na aorta torácica proximal. Existem várias semelhanças entre a fisiopatologia do desenvolvimento da placa de aterosclerose e a remodelação miocárdica. Por causa disso, formulou-se a hipótese de que a avaliação de pacientes com AVC e AIT, por meio do ecocardiograma transtorácico ((ETT), pode identificar características associadas com risco aumentado de placa de aterosclerose em aorta. Os objetivos desse estudo foram: 1) avaliar a incidência de placa de aterosclerose em aorta torácica de pacientes com história de AVC e AIT prévios, por meio do ecocardiograma transesofágico (ETE); 2) avaliar se existe associação entre a presença dessas placas e sinais de remodelação ventricular, observados por meio do ETT; e, finalmente, 3) analisar os níveis séricos de proteína C reativa de alta sensibilidade (PCRas), nesses pacientes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Atherosclerosis plaque in the thoracic aorta is an important cause of acute cerebrovascular events. It would be caused by migration of thrombi and cholesterol cristals released from complex plaques, located at the proximalis thoracic aorta, to the cerebral circulation. Because there are several similarities between the physiopathology of atherosclerosis plaque development and myocardial remodeling. We hypothesized that patients with cerebrovascular events, and atherosclerosis plaque have cardiac morpho-functional alterations. The objectives of the present study were: 1) to evaluate the incidence of thoracic aorta artherosclerosis plaques in patients with a previous cerebrovascular events history, by transesophageal echocardiogram (TEE); 2) to evaluate if there is an association between the presence of plaques and signs of ventricular remodeling, observed by means of transthoracic echocardiogram; and, 3) to analyze the high sensitivity C-reactive protein (hs-CRP) seric levels, in those patients. One hundred and sixteen patients (79 male) with a previous... (Complete abstract click electronic address below) / Doutor

Plasma triacylglycerols (TG) are elevated in diabetes, metabolic syndrome, obesity, and dyslipidemia. Very-low density lipoprotein (VLDL) is the main plasma carrier of TG and the direct metabolic precursor of low-density lipoprotein (LDL), the main carrier of plasma cholesterol and the major causative risk factor for atherosclerosis. Binding of LDL to heparan sulfate on the arterial wall initiates retention and modifications of LDL in the arterial intima, triggering atherosclerosis. Studies presented in this dissertation show that variations in TG levels and lipoprotein binding to heparin, a model for heparan sulfate, alter the structural and biochemical stability of VLDL and LDL, and increase their atherogenic potential. The molecular consequences of variations in the lipoprotein TG content and LDL-heparin binding were determined by combining heparin affinity chromatography with biochemical, spectroscopic and electron microscopic techniques. Remodeling of human VLDL and LDL by thermal denaturation was used to mimic key aspects of lipoprotein remodeling in vivo. Our studies revealed that increasing the TG content in VLDL promotes changes in the lipoprotein size and release of the exchangeable apolipoproteins. Similarly, increased TG content in LDL promotes lipoprotein remodeling and fusion. Additionally, an increase in TG content increases lipoprotein susceptibility to oxidation and lipolysis, thereby promoting the generation of free fatty acids that augment fusion. Consequently, TG-induced destabilization may be a general property of plasma lipoproteins. Our studies showed that binding to heparin initiates irreversible pro-atherogenic remodeling of human LDL. As a result of heparin binding, LDL showed decreased structural stability and increased susceptibility to hydrolysis and fusion. Further, phospholipid hydrolysis and/or glycation of LDL (as occurs in diabetes) increased the proteolytic susceptibility of apolipoprotein (apo)B (the major apolipoprotein of VLDL and LDL) and its heparin binding affinity. LDL derived from hyperglycemic patients with type-2 diabetes, became particularly destabilized following heparin binding causing apoB fragmentation and LDL fusion. In summary, binding to heparin alters apoB conformation and triggers pro-atherogenic LDL modifications including proteolysis, lipolysis and structural destabilization. Furthermore, phospholipid lipolysis and glycation of LDL in vitro strengthen its binding to heparin. Together, these findings help establish a mechanistic link between diabetes and atherosclerosis.