O POLIMORFISMO 894G>T DO GENE DA ÓXIDO NÍTRICO SINTASE ENDOTELIAL E SUA ASSOCIAÇÃO COM DOENÇA CORONÁRIA

O endotélio cumpre um papel fundamental na vasodilatação fisiológica e na proteção da parede arterial frente aos processos de trombose e aterosclerose, assim como na resposta à lesão provocada pela angioplastia ou implante de stent intracoronário. Essa função protetora é exercida, entre outros mecanismos, através da síntese e liberação de óxido nítrico (NO) pelacélula endotelial. O NO inibe a adesão e a agregação plaquetária, assim como provoca a desagregação de agregado plaquetário. Inibe também a mitogênese e a proliferação de células de músculo liso vascular, assim como a quimiotaxia e a adesão de polimorfonucleares neutrófilos ao endotélio. O NO é sintetizado na célula endotelial, a partir da L-Arginina, pela NO sintase endotelial constitutiva (NOSec), uma enzima constitutiva codificada por um gene localizado nocromossomo 7q35-36, contendo 26 éxons que ocupam 21 quilobases. Foram descritos alguns polimorfismos deste gene, entre os quais, o polimorfismo 894G>T, presente no éxon 7 do gene da NOSec. Este polimorfismo consiste na substituição de uma base guanina por uma timina no nucleotídeo 894 do gene; esta mutação resulta na substituição de um aminoácido glutamato por aspartato na posição 298 da NOSec (Glu298Asp). Nesta revisão, descreve-se a possívelassociação desse polimorfismo com a doença coronária, destacando algumas contribuições de nosso grupo de pesquisa.Unitermos: Óxido nítrico sintase endotelial constitutiva, gene, polimorfismo, doença coronária

Association between Vascular Remodelling and Necrotic Core in Coronary Arteries: Analysis by Intracoronary Ultrasound with Virtual Histology®

ABSTRACTBackgroundAnatomopathological studies suggest an association of positive vascular remodeling and vulnerable coronary plaques. The objective of this study was to verify whether there is a correlation between positive vascular remodeling and necrotic core in atherosclerotic coronary lesions.MethodsWe studied 270 cross sections obtained by Virtual Histology® in 30 patients who had positive remodeling in coronary artery segments with lesions > 50%, identified by coronary angiography. Seven cross sections were assessed per segment of coronary artery, including the cross section with the highest remodeling index, denominated cross section of interest (cross section 4).ResultsMean age was 60.8±8.8 years, 80% were male and 30% were diabetic. Unstable angina was the most frequent clinical presentation (56.6%) and the left anterior descending artery was the most analyzed vessel (43%). The vessel reference area was 15.5±4.9mm2 and the remodeling index in cross section 4 was 1.2±0.1. Repeated measures analysis of variance showed a higher percentage of necrotic core in the cross section of interest (P < 0.001). We observed a positive correlation of coronary artery remodeling and necrotic core (r = 0.79; P < 0.001).ConclusionsPositive coronary artery remodeling is associated to the presence of necrotic core, which characterizes vulnerable atherosclerotic plaques. The search for positive arterial remodeling may be a useful strategy for detecting vulnerable plaques before rupture

Modelo bioexperimental de indução de proliferação neointimal vascular em suínos

O objetivo do presente trabalho foi desenvolver um modelo experimental de indução de proliferaçãoneointimal vascular (reestenose) em suínos, fenômeno freqüentemente observado após a realização deintervenções coronarianas percutâneas em humanos (angioplastia e implante de stents). Para isso foicriado um laboratório de hemodinâmica experimental no Hospital Veterinário da ULBRA com o intuitode desenvolver e implementar tal modelo, visando a criação de técnicas de lesão vascular simuladores dereestenose, através do implante de endopróteses (stents) sobre-dimensionados. Concomitante a esse objetivoo modelo servirá para desenvolver métodos e técnicas para tratar, prevenir ou até mesmo impedir areestenose. Na fase inicial foram operados 7 suínos jovens, implantando pelo menos dois stents em cada animal, seguido de re-intervenção em 28 dias com avaliação ultrasonográfica e por histologia virtual e testede algumas drogas anti-proliferativas. O índice de reestenose assim obtido foi de 93,3%.Palavras-chave: reestenose, angioplastia coronária, stents, ultra-som

Protocolo experimental de indução de proliferação neointimal vascular em modelo de arterias coronárias suínas

O objetivo foi desenvolver e implementar modelo experimental de indução de hiperproliferação neointimal emsuínos (lesões vasculares simuladoras de reestenose). De Ago/2006 a Set/2008, 55 suínos da raça Large Whiteforam submetidos a cateterismo cardíaco seguido de lesão vascular e, observados durante 28, 56 ou 84 dias.Após estes períodos, foram realizados cateterismo cardíaco e IVUS e ACTP com droga experimental ou IVUS e análise histológica da artéria coronária. Foram realizados 86 implantes de stents, 82 IVUS, 51 ACTP e 43 testesde drogas, totalizando 262 procedimentos (média de 4,8 procedimentos/animal). A taxa de reestenose binária foide 89,0% (65/73 implantes), o que significa que o modelo foi implantado de forma satisfatória.Palavras-chaves: Angioplastia coronária, modelo experimental suíno, neoíntima, reestenose, stent

Synthesis, characterization and in vitro anticancer activity of Novel 8,4’ : oxyneolignan analogues

Neolignans are a class of natural products with a wide range of biological effects. These substances are of great synthetic and biological interest, especially in searching for novel anticancer agents. In this paper, we report the synthesis of a new subclass of 8,4’-oxyneolignan analogues (β-ketoethers and β-ketoesters) and their cell viability assay on twenty four different cancer cells, among leukemias and carcinomas. Three compounds inhibited the growth of most human cancer cells. 2-Oxo-2-phenylethyl(2E)-3-[4-(2-oxo-2-phenylethoxy) phenyl]prop-2-enoate showed an antiproliferative activity superior to doxorubicin for U-87, U-138 MG and H1299 cell types and (E)-2-oxo-2-phenylethyl 3-(3-methoxy-4-(2-oxo-2-phenylethoxy)phenyl)acrylate was found to be very selective, demonstrating a growth inhibition of 92.0% against KG-1 cells. Furthermore, 1-oxo-1-phenylpropan-2-yl cinnamate exhibited significant inhibition activity in a range of 52.2 to 91.2% against twelve kinds of leukemia cell lines, revealing excellent results and very comparable to the reference drug

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

ATLANTIC-PRIMATES: a dataset of communities and occurrences of primates in the Atlantic Forests of South America

Primates play an important role in ecosystem functioning and offer critical insights into human evolution, biology, behavior, and emerging infectious diseases. There are 26 primate species in the Atlantic Forests of South America, 19 of them endemic. We compiled a dataset of 5,472 georeferenced locations of 26 native and 1 introduced primate species, as hybrids in the genera Callithrix and Alouatta. The dataset includes 700 primate communities, 8,121 single species occurrences and 714 estimates of primate population sizes, covering most natural forest types of the tropical and subtropical Atlantic Forest of Brazil, Paraguay and Argentina and some other biomes. On average, primate communities of the Atlantic Forest harbor 2 ± 1 species (range = 1–6). However, about 40% of primate communities contain only one species. Alouatta guariba (N = 2,188 records) and Sapajus nigritus (N = 1,127) were the species with the most records. Callicebus barbarabrownae (N = 35), Leontopithecus caissara (N = 38), and Sapajus libidinosus (N = 41) were the species with the least records. Recorded primate densities varied from 0.004 individuals/km 2 (Alouatta guariba at Fragmento do Bugre, Paraná, Brazil) to 400 individuals/km 2 (Alouatta caraya in Santiago, Rio Grande do Sul, Brazil). Our dataset reflects disparity between the numerous primate census conducted in the Atlantic Forest, in contrast to the scarcity of estimates of population sizes and densities. With these data, researchers can develop different macroecological and regional level studies, focusing on communities, populations, species co-occurrence and distribution patterns. Moreover, the data can also be used to assess the consequences of fragmentation, defaunation, and disease outbreaks on different ecological processes, such as trophic cascades, species invasion or extinction, and community dynamics. There are no copyright restrictions. Please cite this Data Paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data. © 2018 by the The Authors. Ecology © 2018 The Ecological Society of Americ