V tomto mezioborovém projektu budou připraveny inovované diamantové povlaky kostních a cévních implantátů pro zvýšení jejich histokompatibility při biomedicínských aplikacích. Implantáty budou založeny na kovech běžně užívaných v medicíně (Ti, Ti-6Al-4V, nerez ocel). Pro další zlepšení funkce budou navíc zkoumány nové materiály s nanočásticemi zlata a diamantu, polymery, samonosnými diamantovými strukturami a jejich kompozity. Hierarchicky organizovaná mikro- a nanostruktura implantátů, jejich povrchové chemické složení a smáčivost budou optimalizovány pomocí laseru a plazmatu. Implantáty budou dále funkcionalizovány kostním morfogenetickým proteinem-7 (BMP-7) pro zvýšení jejich osteointegrace nebo heparinem pro zvýšení regenerace endotelu a prevenci restenózy. Nově vyvinuté materiály budou testovány in vitro především z hlediska imunitní aktivace buněk. Vybrané materiály pak budou implantovány in vivo do tibie a krčních tepen králíka a následně bude histologicky sledována reakce přilehlých i vzdálených tkání.; In this interdisciplinary project, innovated diamond coatings will be prepared on bone and vascular implants in order to enhance their histocompatibility for biomedical applications. The implants will be based on metallic substrates used in medicine (Ti, Ti-6Al-4V, stainless steel). In addition, novel types of materials with embedded gold and diamond nanoparticles, polymers, self-standing diamond structures and composites will be developed for further enhanced implant functionality. We will optimize hierarchically organized micro- and nano-structured implants as well as their surface chemistry and wettability by lasers and plasma treatments. The implants will be further functionalized using BMP-7 for enhancing their osseointegration or heparin for promoting endothelial regeneration and preventing restenosis. The developed constructs will be tested and immunologically screened in cultures of bone and vascular cells. The most promising implants will be evaluated in vivo by implantation into the tibia or carotid arteries of rabbits, followed by histological analysis.

• MeSH
• biokompatibilní materiály terapeutické užití   MeSH
• experimenty na zvířatech MeSH
• intravitální mikroskopie MeSH
• kostní morfogenetický protein 7 MeSH
• kovové nanočástice terapeutické užití   MeSH
• nanodiamanty terapeutické užití   MeSH
• polymery terapeutické užití   MeSH
• protézy a implantáty MeSH
• regenerativní lékařství MeSH
• techniky in vitro MeSH
• testování materiálů MeSH
• tkáňové inženýrství MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• biomedicínské inženýrství
• technika lékařská, zdravotnický materiál a protetika
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

• MeSH
• morfogeneze MeSH
• srdce anatomie a histologie   fyziologie   MeSH
• vývojová biologie MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• vysokoškolské kvalifikační práce MeSH

• Konspekt
• Anatomie člověka a srovnávací anatomie
• NLK Obory
• anatomie
• biologie
• fyziologie

AIMS: The cardiac conduction system (CCS) is progressively specified during development by interactions among a discrete number of transcription factors (TFs) that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain TFs with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity; however, the basis for these alterations has not been established. Here, we studied the role of Meis TFs in cardiomyocyte development and function during mouse development and adult life. METHODS AND RESULTS: We studied Meis1 and Meis2 conditional deletion mouse models that allowed cardiomyocyte-specific elimination of Meis function during development and inducible elimination of Meis function in cardiomyocytes of the adult CCS. We studied cardiac anatomy, contractility, and conduction. We report that Meis factors are global regulators of cardiac conduction, with a predominant role in the CCS. While constitutive Meis deletion in cardiomyocytes led to congenital malformations of the arterial pole and atria, as well as defects in ventricular conduction, Meis elimination in cardiomyocytes of the adult CCS produced sinus node dysfunction and delayed atrio-ventricular conduction. Molecular analyses unravelled Meis-controlled molecular pathways associated with these defects. Finally, we studied in transgenic mice the activity of a Meis1 human enhancer related to an single-nucleotide polymorphism (SNP) associated by Genome-wide association studies (GWAS) to PR (P and R waves of the electrocardiogram) elongation and found that the transgene drives expression in components of the atrio-ventricular conduction system. CONCLUSION: Our study identifies Meis TFs as essential regulators of the establishment of cardiac conduction function during development and its maintenance during adult life. In addition, we generated animal models and identified molecular alterations that will ease the study of Meis-associated conduction defects and congenital malformations in humans.

• MeSH
• akční potenciály MeSH
• fenotyp MeSH
• homeodoménové proteiny * genetika   metabolismus   MeSH
• kardiomyocyty * metabolismus   patologie   MeSH
• kontrakce myokardu MeSH
• myši knockoutované MeSH
• nodus sinuatrialis metabolismus   patofyziologie   MeSH
• převodní systém srdeční * metabolismus   patofyziologie   růst a vývoj   MeSH
• srdeční arytmie patofyziologie   metabolismus   genetika   MeSH
• srdeční frekvence * MeSH
• transkripční faktor Meis1 * genetika   metabolismus   nedostatek   MeSH
• věkové faktory MeSH
• vrozené srdeční vady metabolismus   genetika   patofyziologie   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The International Cardiovascular Anatomy, Development, and Regeneration meeting was held from 18-20 September 2024, in Prague, Czech Republic, supported by the European Society of Cardiology's Working Group on Development, Anatomy, and Pathology. Hosted at the Institute of Anatomy, First Faculty of Medicine, the event began with a hands-on workshop on normal and malformed human hearts, covering morphology, echocardiographic imaging, and rare congenital cases. The session allowed participants to examine and image both normal and malformed hearts. The main conference featured nine platform sessions on topics including pediatric cardiology, cardiac progenitors biology, congenital heart disease mechanisms, and cardiac regeneration. Highlights included two keynote lectures on cardiac genetics and development. In keeping with an established, decades-long tradition, the conference is a well-attended event, marking significant engagement in the latest cardiovascular research. The next appointment will be in Granada, Spain, 15-17 October 2025.

• Publikační typ
• kongresy MeSH

BACKGROUND: The ventricular trabeculae play a role, among others, in the impulse spreading in ectothermic hearts. Despite the morphological similarity with the early developing hearts of endotherms, this trabecular function in mammalian and avian embryos was poorly addressed. RESULTS: We simulated impulse propagation inside the looping ventricle and revealed delayed apical activation in the heart with inhibited trabecular growth. This finding was corroborated by direct imaging of the endocardial surface showing early activation within the trabeculae implying preferential spreading of depolarization along with them. Targeting two crucial pathways of trabecular formation (Neuregulin/ErbB and Nkx2.5), we showed that trabecular development is also essential for proper conduction patterning. Persistence of the slow isotropic conduction likely contributed to the pumping failure in the trabeculae-deficient hearts. CONCLUSIONS: Our results showed the essential role of trabeculae in intraventricular impulse spreading and conduction patterning in the early endothermic heart. Lack of trabeculae leads to the failure of conduction parameters differentiation resulting in primitive ventricular activation with consequent impact on the cardiac pumping function.

• MeSH
• neureguliny MeSH
• savci MeSH
• srdce * MeSH
• srdeční komory * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The Achilles tendon (AT) is the strongest tendon of the human body. The knowledge of AT anatomy is a basic prerequisite for the successful treatment of acute and chronic lesions. The structure of the AT results from a complicated fusion of three parts: the tendons of the medial and lateral gastrocnemius and the soleus muscles. From proximal to distal, the tendon fibers twist in a long spiral into a roughly 90° internal rotation. The tendon is narrowest approximately 5-7 cm above its calcaneal insertion and from there it expands again. The topography of the footprints of the individual AT components reflects the tendon origins. The anterior (deep) AT fibers insert into the middle third of the posterior aspect of the calcaneal tuberosity, the posterior (superficial) fibers pass over the calcaneal tuberosity and fuse with the plantar aponeurosis. A deep calcaneal bursa is interposed between the calcaneal tuberosity and the AT anterior surface. The AT has no synovial sheath but is covered along its entire length with a sliding connective tissue, the paratenon which is, however, absent on its anterior surface. The AT is supplied by the posterior tibial artery (PTA) and the peroneal artery (PA). Motor innervation of the triceps surae muscle is provided by fibers of the tibial nerve which also gives off sensitive fibers for the AT. Sensitive innervation is also provided via the sural nerve. The sural nerve crosses the AT approximately 11 cm proximal to the calcaneal tuberosity. The forces acting on the AT during exercise may be up to 12 times the body weight. Physiological stretching of AT collagen fibers ranges between 2% and 4% of its length. Stretching of the tendon over 4% results in microscopic failure and stretching beyond 8% in macroscopic failure.

• MeSH
• Achillova šlacha * anatomie a histologie   MeSH
• anatomické modely MeSH
• kosterní svaly anatomie a histologie   inervace   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Atrioventricular (AV) accessory pathways (APs) provide additional electrical connections between the atria and ventricles, resulting in severe electrical disturbances. It is generally accepted that APs originate in the altered annulus fibrosus maturation in the late prenatal and perinatal period. However, current experimental methods cannot address their development in specific locations around the annulus fibrosus because of the inaccessibility of late fetal hearts for electrophysiological investigation under physiological conditions. In this study, we describe an approach for optical mapping of the retrogradely perfused chick heart in the last third of the incubation period. This system showed stability for electrophysiological measurement for several hours. This feature allowed analysis of the number and functionality of the APs separately in each clinically relevant position. Under physiological conditions, we also recorded the shortening of the AV delay with annulus fibrosus maturation and analyzed ventricular activation patterns after conduction through APs at specific locations. We observed a gradual regression of AP with an area-specific rate (left-sided APs disappeared first). The results also revealed a sudden drop in the number of active APs between embryonic days 16 and 18. Accessory myocardial AV connections were histologically documented in all positions around the annulus fibrosus even after hatching. The fact that no electrically active AP was present at this stage highlights the necessity of electrophysiological evaluation of accessory atrioventricular connections in studying AP formation.NEW & NOTEWORTHY We present the use of retrograde perfusion and optical mapping to investigate, for the first time, the regression of accessory pathways during annulus fibrosus maturation, separately examining each clinically relevant location. The system enables measurements under physiological conditions and demonstrates long-lasting stability compared with other approaches. This study offers applications of the model to investigate electrical and/or functional development in late embryonic development without concern about heart viability.

• MeSH
• akční potenciály * MeSH
• kuřecí embryo MeSH
• nodus atrioventricularis embryologie   patofyziologie   MeSH
• perfuze MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Autologous vein grafts are widely used for bypass procedures in cardiovascular surgery. However, these grafts are susceptible to failure due to vein graft disease. Our study aimed to evaluate the impact of the latest-generation FRAME external support on vein graft remodeling in a preclinical model. METHODS: We performed autologous internal jugular vein interposition grafting in porcine carotid arteries for one month. Four grafts were supported with a FRAME mesh, while seven unsupported grafts served as controls. The conduits were examined through flowmetry, angiography, macroscopy, and microscopy. RESULTS: The one-month patency rate of FRAME-supported grafts was 100% (4/4), whereas that of unsupported controls was 43% (3/7, Log-rank p = 0.071). On explant angiography, FRAME grafts exhibited significantly more areas with no or mild stenosis (9/12) compared to control grafts (3/21, p = 0.0009). Blood flow at explantation was higher in the FRAME grafts (145 ± 51 mL/min) than in the controls (46 ± 85 mL/min, p = 0.066). Area and thickness of neo-intimal hyperplasia (NIH) at proximal anastomoses were similar for the FRAME and the control groups: 5.79 ± 1.38 versus 6.94 ± 1.10 mm2, respectively (p = 0.558) and 480 ± 95 vs. 587 ± 52 μm2/μm, respectively (p = 0.401). However, in the midgraft portions, the NIH area and thickness were significantly lower in the FRAME group than in the control group: 3.73 ± 0.64 vs. 6.27 ± 0.64 mm2, respectively (p = 0.022) and 258 ± 49 vs. 518 ± 36 μm2/μm, respectively (p = 0.0002). CONCLUSIONS: In our porcine model, the external mesh FRAME improved the patency of vein-to-carotid artery grafts and protected them from stenosis, particularly in the mid regions. The midgraft neo-intimal hyperplasia was two-fold thinner in the meshed grafts than in the controls.

• Publikační typ
• časopisecké články MeSH

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.

• MeSH
• aortální insuficience metabolismus   patologie   chirurgie   MeSH
• aortální stenóza * metabolismus   patologie   chirurgie   MeSH
• extracelulární matrix - proteiny * metabolismus   analýza   MeSH
• fibróza * metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezikomorová přepážka patologie   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The heart is capable of extensive adaptive growth in response to the demands of the body. When the heart is confronted with an increased workload over a prolonged period, it tends to cope with the situation by increasing its muscle mass. The adaptive growth response of the cardiac muscle changes significantly during phylogenetic and ontogenetic development. Cold-blooded animals maintain the ability for cardiomyocyte proliferation even in adults. On the other hand, the extent of proliferation during ontogenetic development in warm-blooded species shows significant temporal limitations: whereas fetal and neonatal cardiac myocytes express proliferative potential (hyperplasia), after birth proliferation declines and the heart grows almost exclusively by hypertrophy. It is, therefore, understandable that the regulation of the cardiac growth response to the increased workload also differs significantly during development. The pressure overload (aortic constriction) induced in animals before the switch from hyperplastic to hypertrophic growth leads to a specific type of left ventricular hypertrophy which, in contrast with the same stimulus applied in adulthood, is characterized by hyperplasia of cardiomyocytes, capillary angiogenesis and biogenesis of collagenous structures, proportional to the growth of myocytes. These studies suggest that timing may be of crucial importance in neonatal cardiac interventions in humans: early definitive repairs of selected congenital heart disease may be more beneficial for the long-term results of surgical treatment.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH