333 resultados para Heart Aneurysm
Resumo:
Apart from its role as a flow generator for ventilation the diaphragm has a circulatory role. The cyclical abdominal pressure variations from its contractions cause swings in venous return from the splanchnic venous circulation. During exercise the action of the abdominal muscles may enhance this circulatory function of the diaphragm. Eleven healthy subjects (25 ± 7 year, 70 ± 11 kg, 1.78 ± 0.1 m, 3 F) performed plantar flexion exercise at ~4 METs. Changes in body volume (ΔVb) and trunk volume (ΔVtr) were measured simultaneously by double body plethysmography. Volume of blood shifts between trunk and extremities (Vbs) was determined non-invasively as ΔVtr-ΔVb. Three types of breathing were studied: spontaneous (SE), rib cage (RCE, voluntary emphasized inspiratory rib cage breathing), and abdominal (ABE, voluntary active abdominal expiration breathing). During SE and RCE blood was displaced from the extremities into the trunk (on average 0.16 ± 0.33 L and 0.48 ± 0.55 L, p < 0.05 SE vs. RCE), while during ABE it was displaced from the trunk to the extremities (0.22 ± 0.20 L p < 0.001, p < 0.05 RCE and SE vs. ABE respectively). At baseline, Vbs swings (maximum to minimum amplitude) were bimodal and averaged 0.13 ± 0.08 L. During exercise, Vbs swings consistently increased (0.42 ± 0.34 L, 0.40 ± 0.26 L, 0.46 ± 0.21 L, for SE, RCE and ABE respectively, all p < 0.01 vs. baseline). It follows that during leg exercise significant bi-directional blood shifting occurs between the trunk and the extremities. The dynamics and partitioning of these blood shifts strongly depend on the relative predominance of the action of the diaphragm, the rib cage and the abdominal muscles. Depending on the partitioning between respiratory muscles for the act of breathing, the distribution of blood between trunk and extremities can vary by up to 1 L. We conclude that during exercise the abdominal muscles and the diaphragm might play a role of an "auxiliary heart."
Resumo:
LncRNAs are transcripts greater than 200 nucleotides in length with no apparent coding potential. They exert important regulatory functions in the genome. Their role in cardiac fibrosis is however unexplored. To identify IncRNAs that could modulate cardiac fibrosis, we profiled the long non-coding transcriptome in the infarcted mouse heart, and identified 1500 novel IncRNAs. These IncRNAs have unique characteristics such as high tissue and cell type specificity. Their expression is highly correlated with parameters of cardiac dimensions and function. The majority of these novel IncRNAs are conserved in human. Importantly, human IncRNAs appear to be differentially expressed in heart disease. Using a computational pipeline, we identified a super-enhancer-associated IncRNA, which is dynamically expressed after myocardial infarction. We named this particular transcript Wisper for «Wisp2 super-enhancer- derived IncRNA ». Interestingly, Wisper expression is overexpressed in cardiac fibroblasts as compared to cardiomyocytes or to fibroblasts isolated from other organs than the heart. The importance of Wisper in the biology of fibroblasts was demonstrated in knockdown experiments. Differentiation of cardiac fibroblast into myofibroblasts in vitro is significantly impaired upon Wisper knockdown. Wisper downregulation in cardiac fibroblasts results in a dramatic reduction of fibrotic gene expression, a diminished cell proliferation and an increase in apoptotic cell death. In vivo, depletion of Wisper during the acute phase of the response to infarction is detrimental via increasing the risk of cardiac rupture. On the other hand, Wisper knockdown following infarction in a prevention study reduces fibrosis and preserves cardiac function. Since WISPER is detectable in the human heart, where it is associated with severe cardiac fibrosis, these data suggest that Wisper could represent a novel therapeutic target for limiting the extent of the fibrotic response in the heart. -- Les long ARN non-codants (IncRNAs) sont des ARN de plus de 200 nucléotides qui ne codent pas pour des protéines. Ils exercent d'importantes fonctions dans le génome. Par contre, leur importance dans le développement de la fibrose cardiaque n'a pas été étudiée. Pour identifier des IncRNAs jouant un rôle dans ce processus, le transcriptome non-codant a été étudié dans le coeur de'souris après un infarctus du myocarde. Nous avons découverts 1500 nouveaux IncRNAs. Ces transcrits ont d'uniques caractéristiques. En particulier ils sont extrêmement spécifiques de sous-populations de cellules cardiaques. Par ailleurs, leur expression est remarquablement corrélée avec les paramètres définissant les dimensions du coeur et la fonction cardiaque. La majorité de ces IncRNAs sont conservés chez l'humain. Certains sont modulés dans des pathologies cardiaques. En utilisant une approche bioinformatique, nous avons identifié un IncRNA qui est associé à des séquences amplificatrices et qui est particulièrement enrichi dans les fibroblastes cardiaques. Ce transcrit a été nommé Wisper pour «Wisp2 super-enhancer-derived IncRNA ». L'importance de Wisper dans la biologie des fibroblastes cardiaques est démontrée dans des expériences de déplétion. En l'absence de Wisper, l'expression de protéines impliquées dans le développement de la fibrose est dramatiquement réduite dans les fibroblastes cardiaques. Ceux-ci montrent une prolifération réduite. Le niveau d'apoptose est largement augmenté. In vivo, la déplétion de Wisper pendant la phase aiguë de l'infarctus rehausse le risque de rupture cardiaque. Au contraire, la réduction de l'expression de Wisper pendant la phase chronique diminue la fibrose cardiaque et améliore la fonction du coeur. Puisque Wisper est exprimé dans le coeur humain, ce transcrit représente une nouvelle cible thérapeutique pour limiter la réponse fibrotique dans le coeur.