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Doctoral Thesis
DOI
10.11606/T.9.2017.tde-06092017-125743
Document
Author
Full name
Ricardo David Couto
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2005
Supervisor
Committee
Maranhao, Raul Cavalcante (President)
Bydlowski, Sergio Paulo
Chacra, Ana Paula Marte
Farsky, Sandra Helena Poliselli
Santos Filho, Raul Dias dos
Title in Portuguese
Deposição de colesterol de uma microemulsão lipídica em fragmentos vasculares removidos de pacientes durante a cirurgia de revascularização miocárdica: estudos in vivo e in vitro
Keywords in Portuguese
Arteriosclerose (Patogenicidade; Estudo)
Doenças cardiovasculares (Estudo clínico)
Hipercolesterolemia (Estudo clínico)
Lipoproteínas (Metabolismo; Estudo)
Lipoproteínas LDL (Metabolismo; Estudo)
Abstract in Portuguese
Como demonstrado em estudos prévios, quando injetada em indivíduos, a microemulsão lipídica rica em colesterol sem proteína (LDE) que mimetiza a composição da LDL adquire apoE no plasma e é captada por receptores de LDL. No presente estudo, a LDE marcada com colesterol-H3(CL) e oleato de colesterol-C14(OC) foi injetada em 20 pacientes com doença arterial coronária antes da cirurgia de revascularização miocárdica. Fragmentos de aorta, artéria radial, artéria torácica interna, veia safena e pericárdio descartados durante a cirurgia foram coletados e analisados para radioatividade juntos com amostras seriadas de plasma. A contagem radioativa de LDE-OC foi maior do que a de LDE-CL em todas amostras de plasma coletadas durante 24h, entretanto a captação de LDE-CL foi expressivamente maior do que a do OC em todos os fragmentos. A captação de LDE-CL pela aorta foi cinco vezes maior do que a de LDE-OC (p=0,0379), quatro vezes maior na artéria torácica interna (p=0,033), dez vezes maior na veia safena (p=0,006) e quatro vezes maior no pericárdio (p=0,010). Apenas na artéria radial a captação não obteve significância estatística (p=0,053). Os estudos in vitro de captação celular, bloqueio e das marcações imuno-histoquímicas confirmaram os achados in vivo. Concluindo, a expressiva captação vascular do CL comparada com à do OC sugere que o CL dissocia-se a partir das partículas da microemulsão e precipita-se nos vasos. Considerando a LDE como um modelo de microemulsão artificial para a LDL, os resultados sugerem que este tipo de deposição do CL na parede vascular pode constituir um novo mecanismo para a aterogênese.
Title in English
Deposition of cholesterol from a lipid .microemulsion in vascular fragments excised from patients during coronary by-pass surgery: in vivo and in vitro studies
Keywords in English
Arteriosclerosis (Pathogenicity; Study)
Cardiovascular diseases (Clinical study)
Hypercholesterolemia (Clinical study)
LDL lipoproteins (Metabolism; Study)
Lipoproteins (Metabolism; Study)
Abstract in English
As shown in previous studies, when injected into subjects, a protein-free cholesterol-rich microemulsion (LDE) that mimics LDL composition acquires apoE in the plasma and is taken-up by LDL receptors. In the current study, LDE labeled with H3-Cholesterol (FC) and C14-Cholesteryl Oleate(CO) was injected into 20 coronary artery disease patients 24h before myocardial revascularization surgery. Fragments of aortic, radial, internal thoracic arteries, safenous vein and pericardium discarded during surgery were collected and analyzed for radioactivity together with serial plasma samples. The radioactive counting of LDE-CO was greater than that of LDE-FC in all the plasma samples collected over 24h, but the uptake of LDE-FC was markedly greater than that of CO in all fragments. The uptake of LDE-FC by aorta was 5-fold greater than that of LDE-CO (p=0,0379), 4-fold greater in the internal thoracic artery (p=0,033), 10-fold greater in safenous vein (p=0,006) and 4-fold greater in pericardium (p=0,010). Only in the radial artery the uptake didn't attains statistical significance (p=0,053). The in vitro studies of cell uptake, blocking and immunohistochemistry marks confirm the in vivo finds. In conclusion, the remarkably greater vessel tissue uptake of FC compared with CO suggests that FC dissociate from the microemulsion particles and precipitate in the vessels. Considering LDE as an artificial microemulsion model for LDL, the results suggests that this type of FC deposition in the arterial wall, might constitute a novel atherogenic mechanism.
 
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Publishing Date
2017-09-06
 
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