FM-CCUL-Livros e Capítulos de Livros
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- Role of microRNAs in the regulation of cardiovascular diseases : focus on remodellingPublication . Almeida, Ana G.; Pinto, Fausto J.; Enguita, Francisco J.MicroRNAs (miRNAs) are a large class of noncoding RNAs that regulate the expression of protein-coding genes at the post-transcriptional level . They are recognized as regulators of biological processes underlying cardiovascular disorders including hypertrophy, ischemic heart disease, valvular disease and arrhythmias. Particularly, circulating miRNAs are promising biomarkers of cardiovascular pathology (1). MiRNAs are small, noncoding, RNA molecules with approximately 22 nucleotides in length, which act as post-transcriptional regulators of gene expression. Individual miRNAs have been demonstrated to negatively regulate the expression of multiple gene transcripts by the cleavage or suppression of translation of a target mRNA. Conversely, the expression of individual genes can be regulated by multiple miRNAs. Since their experimental description in 1993 (2), a large number of miRNAs known by their gene-regulatory roles in different biological processes, have been catalogued. In fact, miRNAs are known to regulate approximately one third of all coding gene transcripts in mammals, showing their importance as key process modulators (3). Regarding cardiovascular diseases, miRNAs have been identified as key regulators of complex biological processes linked to several conditions as presented above, including left ventricular remodelling, atherosclerosis and myocardial infarction, heart failure, hypertension and arrhythmias (1). miRNAs are expressed in the cardiovascular system, but their role in cardiovascular diseases has not yet been entirely clarified. Moreover, since the discovery that miRNAs are present in the circulation, they have been investigated as novel biomarker as presented bellow. Only 3% of the human genome codes for proteins. Nevertheless, while noncoding RNAs will not act for coding into proteins they modulate all genomic functions. These noncoding RNAs include short miRNAs with approximately 22 nucleotides) and longer, with >200 nucleotides, long noncoding RNAs (lncRNAs) with important biological functions (4) since they are now clearly recognised to play key roles in gene regulation and may simultaneously represent diagnostic and prognostic biomarkers in cardiovascular diseases. (5,6) there are in excess of 2000 human miRNAs (catalogued in mirBase (http://www.mirbase.org) (7). Of note, the key feature of the mechanism of action of miRNAs is that a single miRNA can regulate the expression of several genes, depending on the specificity of the target sequence. On the other side, individual genes can be regulated by different miRNAs particularly if they involve complementary sequences for more than one miRNA. These factors lead to a highly complex regulatory mechanism, often difficult to understand. (8,9). In the healthy adult heart, data from a large sequencing project and other sequential studies, has identified a number of miRNAs that are highly expressed in healthy cardiac tissue and thus expected to play a key role in both normal cardiac function and disease. (10,11) These include miR-1, miR-16, miR-27b, miR-30d, miR-126, miR-133, miR-143, miR-208 and the let-7 family. However, many others have been identified and are now under study. The concept of miRNA-based therapeutics has been emerging and under development, with synthetic antagonists of miRNAs (antagomiRs or antimirs) and very promising in animal models but awaiting new advances in phase II human trials, still in its infancy (12,13). miRNAs clearly intervene in physiological and pathological processes in the cardiovascular diseases. We will review miRNA biology and its role on LV remodeling in myocardial infarction, heart failure, hypertension and aortic stenosis as additionally a note will be provided on the potential of miRNAs for therapeutics.
- Hypothalamic control of sleep-wake circadian cyclePublication . Meira e Cruz, Miguel; Laranjo, Sérgio; Rocha, IsabelSleep-wake cycle is probably the most truthful signature of life. These unavoidable interchangeable states are together the matrix for all that occurs in physiology, and its rhythms are regulated by homeostatic and circadian processes involving different neuronal structures and distinct neural substrates. Hypothalamic regulation of sleep-wake cycle becomes of relevance as several neuropeptide-producing neurons involved in sleep and wakefulness regulation are located there. In this chapter, we provide a review of the hypothalamic regulation of sleep-wake cycle, focusing on the hypocretin system and melanin-concentrating hormone (MCH)-producing neurons located in the lateral hypothalamic area (LHA).
- Inflammation and autonomic functionPublication . Leal, Ângela; Carvalho, Mafalda; Rocha, Isabel; Mota-Filipe, HelderInflammation is generally a temporary and limited condition but may lead to a chronic one if immune and physiological homeostasis are disrupted. The autonomic nervous system has an important role in the short- and, also, long-term regulation of homeostasis and, thus, on inflammation. Autonomic modulation in acute and chronic inflammation has been implicated with a sympathetic interference in the earlier stages of the inflammatory process and the activation of the vagal inflammatory reflex to regulate innate immune responses and cytokine functional effects in longer processes. The present review focuses on the autonomic mechanisms controlling proinflammatory responses, and we will discuss novel therapeutic options linked to autonomic modulation for diseases associated with a chronic inflammatory condition such as sepsis.