Emeryho‐Dreifussova svalová dystrofie (EDMD) patří k vzácným genetickým onemocněním, kde je hlavní příčinou porucha genů kódujících jaderné membránové proteiny. Neurologické příznaky bývají méně vyjádřené a jsou i pro pacienty méně limitující. Naopak dominující jsou kardiální příznaky s poruchami tvorby a převodu vzruchu (sick sinus syndrom, AV blokády, síňové arytmie) či výskytem dilatační kardiomyopatie. Tyto projevy jsou klinicky závažnější a je nutné na ně u pacientů s EDMD myslet. V článku uvádíme soubor deseti nemocných s EDMD, kde poukazujeme na různorodost a závažnost kardiálních obtíží včetně nutnosti dlouhodobé dispenzarizace v rámci multidisciplinárního týmu.
Emery-Dreifuss muscular dystrophy (EDMD) belongs to a rare genetic diseases with disturbances of the genes encoding nuclear membrane proteins. Neurological symptoms are less pronounced and not too limiting for EDMD patients; however, dominant cardiac symptoms with conduction impairment (AV block, atrial arrhythmias) and/or cardiomyopathy are the most serious manifestations of EDMD. We present 10 patients with EDMD, pointing out the variability and severity of cardiac problems, including long-term medical care within the approach of the multidisciplinary medical team.
- Klíčová slova
- CLOPIDOGREL,
- MeSH
- arytmogenní dysplazie pravé komory genetika MeSH
- dilatační kardiomyopatie genetika MeSH
- Fabryho nemoc MeSH
- familiární hypertrofická kardiomyopatie MeSH
- farmakogenetika MeSH
- genetické poradenství etika MeSH
- genetické testování MeSH
- individualizovaná medicína MeSH
- kardiovaskulární nemoci * genetika MeSH
- lékařská genetika metody MeSH
- lidé MeSH
- Marfanův syndrom MeSH
- nemoci srdce * genetika MeSH
- syndrom dlouhého QT MeSH
- vrozené srdeční vady genetika MeSH
- warfarin škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
Current knowledge on the renin-angiotensin system (RAS) indicates its central role in the pathogenesis of cardiovascular remodelling via both hemodynamic alterations and direct growth and the proliferation effects of angiotensin II or aldosterone resulting in the hypertrophy of cardiomyocytes, the proliferation of fibroblasts, and inflammatory immune cell activation. The noncoding regulatory microRNAs has recently emerged as a completely novel approach to the study of the RAS. A growing number of microRNAs serve as mediators and/or regulators of RAS-induced cardiac remodelling by directly targeting RAS enzymes, receptors, signalling molecules, or inhibitors of signalling pathways. Specifically, microRNAs that directly modulate pro-hypertrophic, pro-fibrotic and pro-inflammatory signalling initiated by angiotensin II receptor type 1 (AT1R) stimulation are of particular relevance in mediating the cardiovascular effects of the RAS. The aim of this review is to summarize the current knowledge in the field that is still in the early stage of preclinical investigation with occasionally conflicting reports. Understanding the big picture of microRNAs not only aids in the improved understanding of cardiac response to injury but also leads to better therapeutic strategies utilizing microRNAs as biomarkers, therapeutic agents and pharmacological targets.
- MeSH
- fibróza MeSH
- kardiomegalie genetika metabolismus patologie MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- myokard metabolismus patologie MeSH
- nemoci srdce genetika metabolismus patologie MeSH
- renin-angiotensin systém * MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- syndrom krátkého QT,
- MeSH
- Brugadův syndrom etiologie genetika MeSH
- chromozomální aberace klasifikace MeSH
- cytogenetika MeSH
- fibrilace komor etiologie genetika MeSH
- genetické testování * klasifikace metody MeSH
- geny MeSH
- kardiomyopatie etiologie genetika klasifikace MeSH
- karyotyp MeSH
- lidé MeSH
- mutace MeSH
- nemoci srdce * etiologie genetika klasifikace MeSH
- srdeční arytmie etiologie genetika klasifikace MeSH
- syndrom dlouhého QT etiologie genetika MeSH
- terminologie jako téma MeSH
- typy dědičnosti MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as both an intracellular protein and soluble excreted cytokine, regulating tissue remodeling and immune-infiltrate in adipose tissue the heart and the kidney. In contrast, the increased expression of OPN has been correlated with the severity of the cardiovascular and renal outcomes associated with obesity. Indeed, OPN expression is at the "cross roads" of visceral fat extension, cardiovascular diseases (CVDs) and renal disorders, in which OPN orchestrates the molecular interactions, leading to chronic low-grade inflammation. The common factor associated with OPN overexpression in adipose, cardiac and renal tissues seems attributable to the concomitant increase in visceral fat size and the increase in infiltrated OPN+ macrophages. This review underlines the current knowledge on the molecular interactions between obesity and the cardiac-renal disorders ruled by OPN.
- MeSH
- inzulinová rezistence genetika MeSH
- ledviny metabolismus patologie MeSH
- lidé MeSH
- myokard metabolismus patologie MeSH
- nemoci ledvin genetika metabolismus patologie MeSH
- nemoci srdce genetika metabolismus patologie MeSH
- nitrobřišní tuk metabolismus MeSH
- obezita genetika metabolismus patologie MeSH
- osteopontin genetika metabolismus MeSH
- tuková tkáň metabolismus MeSH
- zánět genetika patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cardiac fibrosis is a final common pathology in inherited and acquired heart diseases that causes cardiac electrical and pump failure. Here, we use systems genetics to identify a pro-fibrotic gene network in the diseased heart and show that this network is regulated by the E3 ubiquitin ligase WWP2, specifically by the WWP2-N terminal isoform. Importantly, the WWP2-regulated pro-fibrotic gene network is conserved across different cardiac diseases characterized by fibrosis: human and murine dilated cardiomyopathy and repaired tetralogy of Fallot. Transgenic mice lacking the N-terminal region of the WWP2 protein show improved cardiac function and reduced myocardial fibrosis in response to pressure overload or myocardial infarction. In primary cardiac fibroblasts, WWP2 positively regulates the expression of pro-fibrotic markers and extracellular matrix genes. TGFβ1 stimulation promotes nuclear translocation of the WWP2 isoforms containing the N-terminal region and their interaction with SMAD2. WWP2 mediates the TGFβ1-induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2.
- MeSH
- dospělí MeSH
- extracelulární matrix - proteiny metabolismus MeSH
- fibróza genetika metabolismus MeSH
- genetická predispozice k nemoci * genetika MeSH
- genové regulační sítě * MeSH
- kardiomyopatie genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myši transgenní MeSH
- myši MeSH
- nemoci srdce genetika metabolismus MeSH
- protein - isoformy MeSH
- protein Smad2 genetika metabolismus MeSH
- regulace genové exprese MeSH
- senioři MeSH
- transformující růstový faktor beta metabolismus MeSH
- ubikvitinligasy genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
It has been previously shown that human cardiac disorders can be modeled with induced pluripotent stem cell differentiated cardiomyocytes (iPSC-CM), which enables to study disease characteristics and pathophysiology in more detail. We have shown that some genetic cardiac diseases can be separated from each other and from healthy controls by applying machine learning methods to calcium transient signals measured from these cells. In this study, separation of four genetic cardiac diseases and controls were studied by applying classification methods such as nearest neighbor searching algorithm, decision trees, least squares support vector machines and random forests to peak data computed from calcium transient signals measured from beating induced pluripotent stem cell-derived (iPSC) cardiomyocytes. The best classification accuracy obtained was 77.8% being very promising. The result strengthens our previous finding that the machine learning method can be exploited to identification of several genetic cardiac diseases, but also to separate mutations in different genes resulting in the same clinical phenotype.
xix, 920 stran : ilustrace ; 25 cm
- MeSH
- genomika metody MeSH
- kardiovaskulární nemoci * genetika MeSH
- nemoci srdce genetika terapie MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
- genetika, lékařská genetika
- NLK Publikační typ
- kolektivní monografie
MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate gene expression. In the last decade, number of evidences showing miRNAs contribution to the regulation of apoptosis, cellular proliferation, differentiation, and other important cellular processes is constantly growing. Specific miRNA expression signatures have been identified in variety of human cancers as well as pathologies of cardiovascular and urinary systems. Our chapter focuses on the potential of urinary miRNAs to serve as biomarkers in uro-oncology, nephrology, and cardiology. We discuss in detail recent knowledge about the origin of urinary miRNAs, their stability, quality control, and their utility as a potential new class of biomarkers in medicine. Finally, we summarize the studies focusing on detection and characterization of urinary miRNAs as potential biomarkers in urologic cancers, nephrology, and cardiology.
- MeSH
- biologické markery moč MeSH
- lidé MeSH
- mikro RNA genetika moč MeSH
- nádory diagnóza genetika patologie moč MeSH
- nemoci srdce diagnóza genetika patologie moč MeSH
- stabilita RNA MeSH
- urologické nemoci diagnóza genetika patologie moč MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Spontaneously hypertensive rats (SHR) develop cardiovascular and metabolic pathology in adulthood when their circadian system exhibits significant aberrances compared with healthy control rats. This study was aimed to elucidate how the SHR circadian system develops during ontogenesis and to assess its sensitivity to changes in maternal-feeding regime. Analysis of ontogenesis of clock gene expression rhythms in the suprachiasmatic nuclei, liver and colon revealed significant differences in SHR compared with Wistar rats. In the suprachiasmatic nuclei of the hypothalamus (SCN) and liver, the development of a high-amplitude expression rhythm selectively for Bmal1 was delayed compared with Wistar rat. The atypical development of the SHR circadian clocks during postnatal ontogenesis might arise from differences in maternal behavior between SHR and Wistar rats that were detected soon after delivery. It may also arise from higher sensitivity of the circadian clocks in the SHR SCN, liver and colon to maternal behavior related to changes in the feeding regime because in contrast to Wistar rat, the SHR SCN and peripheral clocks during the prenatal period and the hepatic clock during the early postnatal period were phase shifted due to exposure of mothers to a restricted feeding regime. The maternal restricted feeding regime shifted the clocks despite the fact that the mothers were maintained under the light/dark cycle. Our findings of the diverse development and higher sensitivity of the developing circadian system of SHR to maternal cues might result from previously demonstrated differences in the SHR circadian genotype and may potentially contribute to cardiovascular and metabolic diseases, which the animal model spontaneously develops.
- MeSH
- cirkadiánní hodiny genetika MeSH
- cirkadiánní rytmus genetika fyziologie MeSH
- exprese genu fyziologie MeSH
- fotoperioda MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- mateřské chování fyziologie MeSH
- metabolické nemoci genetika metabolismus MeSH
- nemoci srdce genetika patofyziologie MeSH
- novorozená zvířata MeSH
- nucleus suprachiasmaticus metabolismus MeSH
- pohybová aktivita fyziologie MeSH
- stravovací zvyklosti fyziologie MeSH
- vývojová regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
