Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 4 uppsatser. Även tryckt utgåva.

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. / 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.

A hipercolesterolemia familiar (HF) é caracterizada por concentrações elevadas de LDL-c e alta prevalência de doença arterial coronária (DAC) precoce. Entretanto, o curso da DAC nos portadores de HF é variável e pode ser influenciado por outros fatores de risco. O objetivo foi avaliar parâmetros clínicos e nutricionais de adultos portadores de HF heterozigótica por estudo do tipo transversal. Coletou-se do prontuário dos pacientes resultados de exames laboratoriais, medidas de pressão arterial e diagnósticos clínicos. Verificou-se a concordância ou não entre as categorias de risco pelos escores de Framingham (ERF) e pelos critérios estabelecidos para os portadores de HF. Antecedentes pessoais e familiares para DAC, tabagismo, atividade física, consumo alimentar de gorduras, fibras e bebidas alcoólicas foram obtidos por questionário e medidas antropométricas foram aferidas. Foram comparados os grupos com e sem Síndrome Metabólica (SM) e os grupos com e sem DAC por análise univariada. Após, foram verificados os fatores determinantes para o desenvolvimento da DAC mediante modelo de regressão multivariada. Foram entrevistados 110 pacientes (68 mulheres) com média de idade de 48,9 ± 16,2 anos. A presença de história familiar de DAC precoce foi relatada por 67 (61,5%) pacientes. A hipertensão foi encontrada em 59 (53,6%), SM em 38 (34,9%), DAC em 30 (27,3%), HDL-c baixo em 28 (25,5%), diabete melito em 17 (15,5%), 25 (22,7%) eram ex-fumantes e 12 (10,9%) tabagistas. Com a comparação das categorias de risco observou-se discrepância em 77,5% dos casos entre os ERF e os critérios estabelecidos para a população de HF. Quanto ao estado nutricional, 47 (42,7%) eram pré-obesos e 61 (55,4%) com circunferência da cintura alterada. O consumo de gorduras, fibras e bebidas alcoólicas foi considerado adequado. Encontrou-se grande número de sedentários (77%). O grupo dos pacientes com SM tinha idade mais avançada (55 vs 46 anos; p = 0,002), maior número de mulheres (76,3%; p = 0,02) e portadores de DAC (42,1%; p = 0,013). O grupo dos coronarianos tinha idade mais avançada (55 vs 47 anos; p = 0,004), mais pacientes do sexo masculino (60%; p = 0,004), maior presença de hipertensos (90%; p = 0,001), exfumantes (40%; p = 0,008), com SM (53,3%; p = 0,013), HDL-c baixo (53,3%; p = 0,001) e antecedente de infarto agudo do miocárdio (IAM) em irmãos (50%; p = 0,012). As medidas antropométricas, o consumo alimentar e a atividade física não foram diferentes entre os grupos. Após análise de regressão multivariada os fatores de risco determinantes para o desenvolvimento da DAC foram HDL-c baixo (OR 8,4; IC 95% 2,7-27,6), sexo masculino (OR 7,3; IC 95% 2,1-24,7), história de IAM em irmãos (OR 3,4; IC 95% 1,1-10,5) e idade avançada (OR 1,06; IC 95% 1,02-1,1). Em nossa população, HDL-c baixo, sexo masculino, história de IAM em irmãos e idade foram fatores independentes para o desenvolvimento da DAC. / Familial hypercholesterolaemia (FH) is characterized by raised concentrations of LDL-c and high prevalence of premature coronary artery disease (CAD). However, the course of the CAD in the FH is variable and can be influenced by other risk factors. The aim of the study was to assess clinical and nutritional parameters in adults with heterozigous FH by a cross sectional study. Laboratory exams, blood pressure measurement and clinical diagnosis were collected. Agreement or not between the categories of risk by Framingham scores and for established criteria for the FH subjects was verified. Personal and familial history for CAD, smoken habit, physical activity, fats, fibers and alcohol consumption were assessed by questionnaire and anthropometric measurement were verified. The groups with and without Metabolic Syndrome (MS) and groups with and without CAD were compared by univariated analysis. After, multivaried analysis (MVA) was used to assess the significance of differences in risk factors. The sample was composed by 110 patients (68 women) with average of age of 48.9 ± 16.2 years. The presence of familial history of premature CAD was detected in 67 (61.5%)subjects. Hypertension was found in 59 (53.6%), MS in 38 (34.9%), CAD in 30 (27.3%), low HDL-c in 28 (25.5%), diabetes in 17 (15.5%), 25 (22,7%) and 12 (10,9%) were respectively former and current smokers. In the comparison of the risk categories discrepancy was observed in 77.5% of the cases between the Framingham scores and the established criteria for the FH population. Analyzing the nutritional profile, 47 (42.7%) were overweight and 61 (55.4%) had increased waist circumference. The consumption of fats, fibers and alcohol were considered satisfactory. A great number of sedentary subjects was found (77%). The patients with MS were older (55 vs. 46 years; p = 0.002), had a greater number of women (76.3%; p = 0.02) and CAD (42.1%; p = 0.013). CAD subjects were older (55 vs. 47 years; p = 0.004), had a higher prevalence of males (60%; p = 0.004), hypertension (90%; p = 0.001), former smokers(40%; p = 0.008), MS (53.3%; p = 0.013), low HDL-c (53.3%; p = 0.001) and history of myocardial infarction in brothers (50%; p = 0.012). There were no differences between the groups regarding anthropometric measurements, consumption of fats, fiber and alcohol and physical activity. After MVA, independent risk factors for CAD were low HDL-c (OR 8.4; CI 95% 2.7-27.6), male gender (OR 7.3; CI 95% 2.1-24.7), history of myocardial infarction in brothers (OR 3.4; CI 95% 1.1-10.5) and advanced age (OR 1.06; CI 95% 1.02-1.1). In our population, low HDL-c, male gender, history of myocardial infarction in brothers and age were independently associated with the risk of CAD.

Estudamos 62 pacientes, que com teste ergométrico positivo, manifestaram angina estável e estavam sob controle farmacológico. Todos apresentavam cinecoronariografia mostrando obstrução >70% em pelo menos uma das principais artérias coronárias. Objetivamos avaliar parâmetros eletrocardiográficos e de pressão arterial, durante procedimento odontológico restaurador sob anestesia local com e sem vasoconstritor em presença de doença arterial coronária. As idades variaram de 39 a 80, média de 58,7±8,8 anos, sendo 51 (82,3%) homens. Trinta pacientes foram randomizados para receber anestesia local com solução de lidocaína a 2% com adrenalina 1:100.000 e os demais para lidocaína a 2% sem vasoconstritor. Todos os pacientes foram submetidos à monitorização ambulatorial da pressão arterial (MAPA) e eletrocardiografia dinâmica por 24 horas, iniciados 2 horas antes do procedimento odontológico. Consideramos 3 períodos de registro: (1) basal - os 60 minutos que antecederam ao procedimento odontológico; (2) procedimento - desde o início da anestesia até o final do procedimento odontológico restaurador; (3) subseqüente completar das 24 horas. A análise de variância com medidas repetidas mostrou que houve elevação significativa da pressão arterial sistólica e diastólica do período basal para o procedimento nos dois grupos estudados (aproximadamente 14mmHg e 5 a 7mmHg) respectivamente, quando analisados separadamente e quando confrontados não apresentaram diferença de comportamento entre si. A freqüência cardíaca não se alterou nos dois grupos estudados. Depressão do segmento ST >1mm ocorreu em 10 (17,9%) pacientes; todos os eventos ocorreram no mínimo 2 horas após o término do procedimento odontológico. Extra - sístoles supra-ventriculares e/ou extra-sístoles ventriculares em número maior do que 10/hora estiveram presentes em 17 (30,4%) pacientes durante as 24 horas e durante o período do procedimento em 7 (12,5%), sendo 4 (13,8%) do grupo que recebeu anestesia sem adrenalina e 3 (11,1%) do grupo que recebeu anestesia com adrenalina e o teste Exato de Fisher não mostrou diferença entre os grupos. Concluímos que não houve diferença em relação ao comportamento de pressão arterial, freqüência cardíaca, evidência de isquemia e arritmias entre os grupos. O uso associado de vasoconstritor mostrou-se, portanto, seguro dentro dos limites do estudo. / We enrolled 62 patients with positive exercise stress test who presented with stable angina and were receiving drug therapy. All had a coronary angiography screening showing >70% obstruction in at least one of the main coronary arteries. The study aimed to compare electrocardiographic and blood pressure parameters during restorative dentistry procedure under local anesthesia, both with and without vasoconstrictor, in the presence of coronary artery disease. Ages ranged from 39 to 80, (mean ± SD) 58.7±8.8 years, 51 (82.3%) of them were male. Thirty patients were randomly assigned to receive 2% lidocaine local anesthesia with 1:100,000 epinephrine, the others receiving 2% lidocaine without vasoconstrictor. All the patients underwent ambulatory blood pressure and 24-hour Holter monitoring, beginning two hours ahead of the dental procedure. Recording were made during (1) baseline - 60-minute period before dental procedure began; (2) procedure - from beginning of anesthesia until the end of the procedure; and (3) subsequent 24-hour period. Analysis of variance with repeat measures showed significant diastolic and systolic blood pressure increases from baseline to the period of the procedure, in the two study groups (approximately 14 mm Hg, and 5 to 7 mm Hg, respectively); both in a separate analysis and in a comparative analysis no significant difference between them could be confirmed. Heart rate did not change in neither of the two groups. ST-segment >1 mm depression was detected in 10 (17.9%) patients; all these events occurred at least two hours after the end of the dentistry procedure. Premature supraventricular systoles and/or premature ventricular systoles in a greater number than 10/hour were seen in 17 (30.4%) patients in the 24-hours period after the procedure; during the procedure they occurred in 7 (12.5%) patients, of whom 4 (13.8%) were in the group without, and 3 (11.1%) in the group with vasoconstrictor. The Fisher\'s exact test revealed no difference between the groups. We concluded that there was no difference of blood pressure, heart rate, evidence of ischemia or arrhythmia episodes between the groups. Thus, the associated use of vasoconstrictor proved to be safe within the limits of this study

Objective: To quantify and compare histopathological differences regarding atherosclerosis and granular media calcinosis (GMC) of ascending aortic aneurysms (AAA), which are associated with aortic stenosis (AS) or aortic regurgitation (AR). Additionally, a subanalysis of patients with bicuspid or tricuspid aortic valve (BAV or TAV), which were contained within the AS and AR group, was conducted. Patients and Methods: From 01/2012 till 12/2015 84 ascending aortic tissue samples were obtained and divided into their convex and concave half during aortic surgery. Aortic surgery was indicated due to AAA in association to AS (AS-AAA group: n = 43) or AR (AR-AAA group: n = 41). Both groups contained 19 patients with TAV. Convex and concave halves of all samples were stained with three different histologic dyes: hematoxylin-eosin (HE) was used as general stain for atherosclerosis, von-Kossa (vKossa) stain and alizarin-red (Ared) stain were used as calcinosis specific dyes. HE stained samples were analyzed using a semi-quantitative score, while calcinosis quantification was carried out by a binary, pixel guided contrast analysis via computer software. Results: In the AR-AAA group, atherosclerosis was two and a half times more often detectable in the concave halves of the tissue samples as in the AS-AAA group (AR-AAA concave: 15 (36%) vs. AS-AAA concave: 6 (13%), p ≤ 0,01). Regarding GMC, tissue samples from AS-AAAs showed a 4,2-4,5% higher mean GMC deposit than their AR-AAA counterparts (p ≤ 0,001). Furthermore, BAV patients within the AS-AAA group showed a 2,1-2,4% higher mean deposit of GMC than their TAV peers (p ≤ 0,002). These finding of higher GMC deposition was consistent for BAV patients contained in the AAA-AR group. Conclusion: AR-AAA are, in comparison with AS-AAA, more prone to develop atherosclerosis. Atherosclerosis will most likely present at the concave curvature of the ascending aorta. AS-AAAs present significant higher mean GMC deposits than AR-AAAs. Combined with a bicuspid morphology of the aortic valve, GMC deposition in AAAs is elevated in comparison to AAAs with TAV morphology. Therefore AS-AAAs with BAV have the highest tendency to develop heavy GMC deposition, compromising the biomechanical structure of the aortic wall.

Enligt Socialstyrelsen år 2019 var hjärt-och kärlsjukdomar den vanligaste dödsanledningen i Sverige och svarade för 31 % av alla dödsfall i landet. Akut kranskärlssjukdom tillhör hjärt- och kärlsjukdomar och är en folksjukdom som drabbar både kvinnor och män i hela västvärlden med högst mortalitet till följd. Kliniska studier har visat att den västerländska kosten med för högt animaliskt proteinintag, för högt intag av raffinerat socker och fett är den primära bakomliggande orsaken till dödsfall i hjärt-kärlsjukdom. Största riskfaktorn för kranskärl-och andra hjärtsjukdomar är arterioskleros (åderförkalkning). En växtbaserad 10 % lågfetthaltig Whole Food Plant Based-diet (WFPB) har visat sig ha en positiv effekt på arteriosklerosprocessen och vidare på hjärt-kärlsjukdomars utveckling. Syftet med detta projekt var att genom en systematisk litteraturstudie undersöka om hjärtsjukdomar, framförallt kranskärlsjukdomar (CAD) kan stagneras och/eller reverseras med hjälp av en lågfetthaltig WFPB-diet. Studien är baserad på 10 vetenskapliga artiklar framtagna ur databaserna CINAHL, PubMed, Google Scholar samt från referenslistan på två av de redan utvalda artiklarna. Samtliga tio artiklar som inkluderats i litteraturstudien valdes genom datainsamling, relevansbedömning och kvalitetsgranskning. För att säkerställa artiklarnas kvalité kvalitetsgranskades de relevanta artiklarna utifrån frågor skapade från en mall från Statens beredning för medicinsk och social utvärdering, SBU. De analyserade mätparametrarna i artiklarna var bl. a. angiografiparametrar, lipidbiomarkörer, anginasymtom, Flödesmedierat vasodilatationstest (FMD) samt Positronemissions tomografi (PET). De flesta granskade studierna visade reversering av CAD, två artiklar visade både reversering och stagnering och en artikel kunde inte bedömas. Stagnering eller reversering av kranskärlsjukdomar kan åstadkommas antingen genom en kombination av dietintervention och andra livstilförändringar som komplement till lipidsänkande medicinsk behandling eller genom endast diet-och andra livstilförändringar. / According to the National Board of Health and Welfare in 2019, cardiovascular disease was the most common cause of death in Sweden and accounted for 31% of all deaths in the country. Acute coronary heart disease belongs to cardiovascular disease and is a common disease that affects both women and men throughout the Western world with the highest mortality as a result. Clinical studies have shown that the Western diet with too high animal protein intake, too high intake of refined sugar and fat is the primary underlying cause of death in cardiovascular disease. The biggest risk factor for coronary heart disease and other heart diseases is arteriosclerosis (atherosclerosis). A plant-based 10% low-fat Whole Food Plant Based Diet (WFPB) has been shown to have a positive effect on the arteriosclerosis process and further on the development of cardiovascular disease. The purpose of this project was to investigate through a systematic literature study whether heart disease, especially coronary heart disease (CAD) can be stagnated and / or reversed with the help of a low-fat WFPB diet. The study is based on 10 scientific articles produced from the databases CINAHL, PubMed, Google Scholar and from the reference list of two of the already selected articles. All ten articles included in the literature study were selected through data collection, relevance assessment and quality review. To ensure the quality of the articles, the relevant articles were quality examined on the basis of questions created from a template from the Swedish Agency for Medical and Social Evaluation, SBU. The analyzed measurement parameters in the articles were for example angiography parameters, lipid biomarkers, angina symptoms, Flow-mediated vasodilation test (FMD) and Positron emission tomography (PET). Most of the studies examined showed reversal of CAD, two articles showed both reversal and stagnation and one article could not be assessed. Stagnation or reversal of coronary heart disease can be achieved either through a combination of dietary intervention and other lifestyle changes in addition to lipid-lowering medical treatment or through dietary and other lifestyle changes only.

<p>Boljom prevencijom aterosklerotskih bolesti i uvođenjem invazivnih procedura endoluminalnim pristupom u lečenju koronarne bolesti i karotidne bolesti, hirur&scaron;ke procedure u poslednje dve decenije postaju sve kompleksnije i teže. Profil pacijenata podvrgnutih revaskularizaciji miokarda postaje sve rizičniji i procentualno se povećava broj polivaskularnih pacijenata za koje je neophodno uraditi dodatne procedure na karotidnim arterijama, bilo da su one urađene simultano, u dva ili tri akta. To su pacijenati koji imaju značajne aterosklerotske lezije na jednoj ili obe karotidne arterije zajedno sa značajnim suženjima koronarnih arterija. Algoritmi koji se nude u projektovanju operativne taktike ni danas nisu strogo definisani i vrlo često zavise od individualne procene i stava hirurga koji izvode ove procedure. Ishod operativnog lečenja ovih pacijenata često zavisi od hirur&scaron;ke taktike i ustanove u kojoj se oni operativno leče. Prediktori ishoda operativnog lečenja bi mogli biti važan faktor u selekcioniranju pacijenata u preporuci taktike operativnog lečenja. U tezi su analizirani klinički aspekti preoperativno i postoperativno, postoperativni mortalitet - 30 dana posle operacije i jednu godinu posle operacije. Analiziran je uticaj faktora: starost, pol, neurolo&scaron;ka disfunkcija, infarkt miokarda do 90 dana pre operacije, nestabilna angina, diabetes mellitus, bilateralna stenoza karotidnih arterija kod 94 pacijenta koji su operisani u Klinici za kardiohirurgiju Instituta za kardiovaskularne bolesti Vojvodine u Sremskoj Kamenici u periodu 2007-2012g. Kod svih je, preoperativno, nađeno da imaju značajne promene na koronarnim i karotidnim arterijama. Pacijenti su podeljeni u dve grupe po tipu izvr&scaron;ene operacije. Prvu grupu su sačinjavali pacijenti koji su operisani u odvojenim operacijama karotidnih arterija i revakularizacije miokarda, a drugi su operisani simultano operacijom karotidnih arterija i revaskularizacijom miokarda. U metodologiji su kori&scaron;ćene metode retrospektivnog i prospektivnog istraživanja. Kori&scaron;ćena je elektronska baza podataka Instituta za kardiovaskularne bolesti Vojvodine, vođen je intervju sa pacijentima. Kori&scaron;ćeni su i pregledi doppler sonografije karotidnih arterija koji su rađeni u drugim ustanovama. Mortalitet-30 dana i jednu godinu posle operacije je bio prihvatljivo nizak, pacijenti su pobolj&scaron;ani u posmatranim parametrima. Neurolo&scaron;ki morbiditet na 30 dana i jednu godinu posle je bio prihvatljivo nizak. Prediktori mortaliteta su bili pu&scaron;enje 30 dana i godinu dana posle operacije u obe grupe. Prediktor morbiditeta 30 dana i jednu godinu nakon operacije bila je hiperlipoproteinemija. Ženski pol je bio nezavisni prediktor mortaliteta u grupi pacijenata operisanih u vi&scaron;e aktova. Pacijenti operisini simultano su bili teži po simptomima ( NYHAklasi) i u većem riziku (EU2 score), ali nisu imali statistički značajno veću smrtnost u odnosu na grupu operisanu u vi&scaron;e aktova.</p> / <p>Surgical procedures have become more complex and difficult in the past two decades due to the better prevention of atherosclerotic diseases and the introduction of invasive procedures with endoluminal approach to treating coronary and carotid artery diseases. The profile of patients undergoing myocardial revascularization is becoming riskier. There is also increase in the percentage of patients with polyvascular disease who need additional procedures on the carotid arteries, whether they are done simultaneously or in two or three acts. These are the patients who have significant atherosclerotic lesions in one or both of the carotid arteries along with the significant narrowing of the coronary arteries. Algorithms that are offered to plan operative tactics are still not strictly defined and often depend on the individual assessment of surgeons and the attitude of certain institutions that perform the procedure. The outcome of surgical treatment of these patients often depends on surgical tactics and the institution in which they are treated. Predictors of surgical treatment outcome could be an important factor for the selection of patients and the recommendation of operative treatment tactics. The thesis analyzed pre- and postoperative clinical aspect as well as 30-day and one-year postoperative mortality. The influence of the following factors was analyzed: age, sex, neurologic dysfunction, myocardial infarction occurring 90 days after surgery, unstable angina, diabetes mellitus, and bilateral carotid artery stenosis in 94 patients that underwent cardiac surgery at the Clinic of Cardiovascular Surgery of the Institute of Cardiovascular Diseases of Vojvodina in Sremska Kamenica in the period from 2007 to 2012. All patients had significant changes on the coronary and carotid arteries. The patients were divided into two groups according to the type of surgery. The first group consisted of the patients who underwent carotid artery surgery and myocardial revascularization separately. The second group of patients underwent carotid artery surgery and myocardial revascularization at the same time. Methods of retrospective and prospective research were used in the methodology. Electronic data base of the Institute of Cardiovascular Diseases of Vojvodina was also used and the patients were interviewed. Doppler of carotid arteries performed both in our institution and in other institutions was used. Mortality, 30-day and one-year post surgery, was acceptably low. The patients were improved in the observed parameters. Neurologic morbidity 30 days and one year after surgery was acceptably low. Smoking 30 days and one year after surgery was predictor of mortality in both groups. Hyperlipoproteinemia 30 days and one year after surgery was predictor of morbidity. Female sex was independent predictor of mortality for the first group of patients. The second group of patients were more complex according to the symptoms (NYHA class) and with greater risk (EU2 score), but their mortality rate was not statistically significant in relation to the first group of patients.</p>

Lípides nitrados (NO2-FA) são apontados como uma nova classe de mediadores lipídicos, podendo atuar como reservatórios endógenos de óxido nítrico (&#8226NO) bem como moduladores pluripotentes de sinalização celular. Recentemente, tem sido sugerido que os doadores de &#8226NO estariam envolvidos na regulação da angiogênese. Evidências contundentes indicam ainda que o processo de neovascularização poderia contribuir para a patogênese de uma serie de condições clínicas, entre elas a aterosclerose. Contudo, apesar de diversos estudos terem explorado os efeitos biológicos dos NO2-FA, os efeitos destes compostos sobre o processo de angiogênese não haviam sido descritos. Dessa maneira, o presente trabalho investigou os efeitos dos NO2-FA (derivados da nitração do ácido linoléico e oléico) noprocesso de angiogênese. Demonstrou-se que os NO2-FA podem atuar como mediadores pró-angiogênicos. Este efeito foi caracterizado em células endoteliais humanas, assim como, em modelos ex vivo e in vivo. Nas células endoteliais, observou-se que os No2-FA não influenciaram a proliferação ou a viabilidade celular, ao passo que estimularam a migração. Demonstrou-se também que os NO2-FA podem modular o brotamento ex vivo de novos vasos, em cultura de anéis de aorta de rato, bem como o processo angiogênico in vivo observado na membrana corioalantóica de embrião de galinha. Adicionalmente, os NO2-FA induziram a expressão do fator de crescimento endotelial vascular (VEGF), que é o principal mediador do processo de angiogênese. Em relação ao mecanismo de ação, os achados sugerem que os efeitos demonstrados seriam via mecanismos dependentes de &#8226NO, uma vez que foram abolidos na presença de um seqüestrador de &#8226NO, enquanto concentrações equivalentes dos lípides precursores não demonstraram qualquer influência nas condições experimentais utilizadas neste estudo. Por fim, os efeitos pró-angiogênicos dos NO2-FA foram mediados pela estabilização da proteína do fator induzível por hipóxia -1&#945; (HIF-1&#945;), uma vez que estes compostos promoveram acúmulo desta proteína e falharam em demonstrar efeitos indutores em células knockdown para o gene HIF-1&#945;. Em conjunto, estes resultados indicam que os NO2-FA podem modular a migração de células endoteliais e estimular o processo de angiogênese resultante da ativação de HIF-1a via mecanismo dependente de &#8226NO. / Nitrated lipids (NO2-FA) are described as a new class of Iipid mediators that are able to act as endogenously nitric oxide (&#8226NO) reservoirs as well as pluripotent cell signaling modulators. Furthermore, recent findings suggest that &#8226NO donors could be involved in the regulation of angiogenesis. Compelling evidence also indicate that the neovascularization process might contribute to the pathogenesis of many clinical conditions, such as atherosclerosis. However, although several studies have explored the NO2-FA biological properties, the effects of these compounds on the angiogenic process remain unknown. Hence, the present study investigated the effects of the NO2-FA (derivates from the nitration of Iinoleic and oleic acids at physiological concentrations) on angiogenesis processo It is demonstrated that the No2-FA could act as pro-angiogenic mediators. This effect was observed not only in human endothelial cells but also in ex vivo and in vivo models. Using endothelial cells, it is showed that NO2-FA failed to affect cell proliferation ar influence cellular viability, but significantly stimulated cell migration. It was also found that the NO2-FA might modulate the ex vivo sprouting of new vessels as well as the in vivo angiogenic process, while inducing the expression of the vascular endothelial growth factor, the main mediator of angiogenesis. The data are consistent with the hypothesis that the observed effects mediated by NO-dependent mechanisms, since the presence of a &#8226NO scavenger abrogated the induced effects, whereas equimolar concentrations of its precursors, showed no effect on angiogenesis under our experimental conditions. Finally, the pro-angiogenic effects of NOrFA were mediated by the stabilization of the hypoxia inducible factor-1&#945; (HIF-1&#945;) protein, because these compounds increased the protein amount and failed to show inductive effects in HIF-1&#945; knockdown cells. Taken together, these findings indicated that NO2-FA might modulate the endothelial cell migration and stimulate the process of angiogenesis by the HIF-1&#945; induction through a &#8226NO-dependent mechanism.

Σκοπός: Διεξάγαμε την παρούσα μελέτη για να καταδείξουμε την ύπαρξη των βρογχικο-στεφανιαίων αναστομώσεων στο πειραματικό μοντέλο του χοίρου. Επιπλέον διερευνήσαμε την επίπτωση της αρτηριοσκλήρυνσης στις βρογχικές αρτηρίες. Υλικό – Μέθοδος: Χρησιμοποιήθηκαν τα παρασκευάσματα καρδιάς και πνευμόνων από 6 χοίρους. Επιπλέον, δείγματα βρογχικών αρτηριών ελήφθησαν από 40 ασθενείς που υποβάλλονταν σε θωρακοτομή. Σημειώθηκαν αναλυτικά οι κλινικοί και εργαστηριακοί παράγοντες κινδύνου για ανάπτυξη αρτηριοσκλήρυνσης. Αποτελέσματα: Με υπολογιστική τομογραφία, ψηφιακή αγγειογραφία και χορήγηση χρωστικής ρητίνης καταδείξαμε το αναστομωτικό δίκτυο μεταξύ των βρογχικών και κυρίως των αριστερών στεφανιαίων αρτηριών σε 5 από τα 6 παρασκευάσματα. Η μικροσκοπική εξέταση των δειγμάτων δεν στοιχειοθέτησε ύπαρξη αθηροσκλήρυνσης, παρά μόνο ύπαρξη ασβεστοποιού σκλήρυνσης του μέσου χιτώνα σε ποσοστό 2.5%, που δεν συσχετίστηκε με τους παράγοντες κινδύνου αρτηριοσκλήρυνσης. Συμπεράσματα: Με δεδομένο ότι βρογχικές αρτηρίες παρουσιάζουν ελάχιστο βαθμό ασβεστοποιού σκλήρυνσης του μέσου χιτώνα., υποθέτουμε ότι θα μπορούσαν να συνδράμουν στη στεφανιαία κυκλοφορία μέσω των προαναφερθεισών αναστομώσεων σε καταστάσεις εκσεσημασμένης στεφανιαίας νόσου. Η μελέτη μας υπογραμμίζει την σπουδαιότητα των βρογχικών αρτηριών και των βρογχικο-στεφανιαίων αναστομώσεων σε περιπτώσεις εμβολισμού των βρογχικών αρτηριών, μεταμοσχεύσεων καρδιάς-πνευμόνων και αντιμετώπισης ανευρυσμάτων θωρακικής αορτής. / Aim of the study: We conducted this study to demonstrate the coronary-bronchial anastomotic routes in a porcine model. Additionally, we estimated the incidence of bronchial arteries arteriosclerosis. Material and Methods: Six heart-lung porcine blocks were used. Furthermore, 40 bronchial arteries were obtained from patients who underwent thoracotomy. Detailed clinical and laboratory atherosclerotic risk factors of the patients were documented. Results: Using CT-scan, Digital Subtraction Angiography and colored latex, we demonstrated communications between the bronchial and coronary circulation in 5 of 6 subjects. Histology revealed no established atherosclerotic lesion and narrowing of the lumen, but medial calcific sclerosis in 2.5%, that was independent from the arteriosclerotic risk factors. Conclusions: As evidence suggests that bronchial arteries only exhibit medial calcific sclerosis, we hypothesize that bronchial arteries can contribute to the coronary flow through the broncho-coronary anastomoses in cases of severe coronary artery disease. Our study emphasizes their importance and their anastomoses to coronaries in cases of embolization, heart-lung transplantation and thoracic aorta aneurysms repair.

Lípides nitrados (NO2-FA) são apontados como uma nova classe de mediadores lipídicos, podendo atuar como reservatórios endógenos de óxido nítrico (&#8226NO) bem como moduladores pluripotentes de sinalização celular. Recentemente, tem sido sugerido que os doadores de &#8226NO estariam envolvidos na regulação da angiogênese. Evidências contundentes indicam ainda que o processo de neovascularização poderia contribuir para a patogênese de uma serie de condições clínicas, entre elas a aterosclerose. Contudo, apesar de diversos estudos terem explorado os efeitos biológicos dos NO2-FA, os efeitos destes compostos sobre o processo de angiogênese não haviam sido descritos. Dessa maneira, o presente trabalho investigou os efeitos dos NO2-FA (derivados da nitração do ácido linoléico e oléico) noprocesso de angiogênese. Demonstrou-se que os NO2-FA podem atuar como mediadores pró-angiogênicos. Este efeito foi caracterizado em células endoteliais humanas, assim como, em modelos ex vivo e in vivo. Nas células endoteliais, observou-se que os No2-FA não influenciaram a proliferação ou a viabilidade celular, ao passo que estimularam a migração. Demonstrou-se também que os NO2-FA podem modular o brotamento ex vivo de novos vasos, em cultura de anéis de aorta de rato, bem como o processo angiogênico in vivo observado na membrana corioalantóica de embrião de galinha. Adicionalmente, os NO2-FA induziram a expressão do fator de crescimento endotelial vascular (VEGF), que é o principal mediador do processo de angiogênese. Em relação ao mecanismo de ação, os achados sugerem que os efeitos demonstrados seriam via mecanismos dependentes de &#8226NO, uma vez que foram abolidos na presença de um seqüestrador de &#8226NO, enquanto concentrações equivalentes dos lípides precursores não demonstraram qualquer influência nas condições experimentais utilizadas neste estudo. Por fim, os efeitos pró-angiogênicos dos NO2-FA foram mediados pela estabilização da proteína do fator induzível por hipóxia -1&#945; (HIF-1&#945;), uma vez que estes compostos promoveram acúmulo desta proteína e falharam em demonstrar efeitos indutores em células knockdown para o gene HIF-1&#945;. Em conjunto, estes resultados indicam que os NO2-FA podem modular a migração de células endoteliais e estimular o processo de angiogênese resultante da ativação de HIF-1a via mecanismo dependente de &#8226NO. / Nitrated lipids (NO2-FA) are described as a new class of Iipid mediators that are able to act as endogenously nitric oxide (&#8226NO) reservoirs as well as pluripotent cell signaling modulators. Furthermore, recent findings suggest that &#8226NO donors could be involved in the regulation of angiogenesis. Compelling evidence also indicate that the neovascularization process might contribute to the pathogenesis of many clinical conditions, such as atherosclerosis. However, although several studies have explored the NO2-FA biological properties, the effects of these compounds on the angiogenic process remain unknown. Hence, the present study investigated the effects of the NO2-FA (derivates from the nitration of Iinoleic and oleic acids at physiological concentrations) on angiogenesis processo It is demonstrated that the No2-FA could act as pro-angiogenic mediators. This effect was observed not only in human endothelial cells but also in ex vivo and in vivo models. Using endothelial cells, it is showed that NO2-FA failed to affect cell proliferation ar influence cellular viability, but significantly stimulated cell migration. It was also found that the NO2-FA might modulate the ex vivo sprouting of new vessels as well as the in vivo angiogenic process, while inducing the expression of the vascular endothelial growth factor, the main mediator of angiogenesis. The data are consistent with the hypothesis that the observed effects mediated by NO-dependent mechanisms, since the presence of a &#8226NO scavenger abrogated the induced effects, whereas equimolar concentrations of its precursors, showed no effect on angiogenesis under our experimental conditions. Finally, the pro-angiogenic effects of NOrFA were mediated by the stabilization of the hypoxia inducible factor-1&#945; (HIF-1&#945;) protein, because these compounds increased the protein amount and failed to show inductive effects in HIF-1&#945; knockdown cells. Taken together, these findings indicated that NO2-FA might modulate the endothelial cell migration and stimulate the process of angiogenesis by the HIF-1&#945; induction through a &#8226NO-dependent mechanism.