scholarly journals 3D curvature-instructed endothelial flow response and tissue vascularization

2020 ◽  
Vol 6 (38) ◽  
pp. eabb3629
Author(s):  
Christian Mandrycky ◽  
Brandon Hadland ◽  
Ying Zheng

Vascularization remains a long-standing challenge in engineering complex tissues. Particularly needed is recapitulating 3D vascular features, including continuous geometries with defined diameter, curvature, and torsion. Here, we developed a spiral microvessel model that allows precise control of curvature and torsion and supports homogeneous tissue perfusion at the centimeter scale. Using this system, we showed proof-of-principle modeling of tumor progression and engineered cardiac tissue vascularization. We demonstrated that 3D curvature induced rotation and mixing under laminar flow, leading to unique phenotypic and transcriptional changes in endothelial cells (ECs). Bulk and single-cell RNA-seq identified specific EC gene clusters in spiral microvessels. These mark a proinflammatory phenotype associated with vascular development and remodeling, and a unique cell cluster expressing genes regulating vascular stability and development. Our results shed light on the role of heterogeneous vascular structures in differential development and pathogenesis and provide previously unavailable tools to potentially improve tissue vascularization and regeneration.

2020 ◽  
Vol 31 (3) ◽  
pp. 205-209
Author(s):  
Julia Leme Gonçalves ◽  
Laís Pereira Giovanini ◽  
Juliana de Lima Lopes ◽  
Marilia Estevão Cornélio ◽  
Marcos Venícios de Oliveira Lopes ◽  
...  

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Henrik A Kjeldsberg ◽  
Aslak W Bergersen ◽  
Kristian Valen-Sendstad

AbstractAutomated tools for landmarking the internal carotid artery (ICA) bends have the potential for efficient and objective medical image-based morphometric analysis. The two existing algorithms rely on numerical approximations of curvature and torsion of the centerline. However, input parameters, original source code, comparability, and robustness of the algorithms remain unknown. To address the former two, we have re-implemented the algorithms, followed by sensitivity analyses. Of the input parameters, the centerline smoothing had the least impact resulting in 6–7 bends, which is anatomically realistic. In contrast, centerline resolution showed to completely over- and underestimated the number of bends varying from 3 to 33. Applying the algorithms to the same cohort revealed a variability that makes comparison of results between previous studies questionable. Assessment of robustness revealed how one algorithm is vulnerable to model smoothness and noise, but conceptually independent of application. In contrast, the other algorithm is robust and consistent, but with limited general applicability. In conclusion, both algorithms are equally valid albeit they produce vastly different results. We have provided a well-documented open-source implementation of the algorithms. Finally, we have successfully performed this study on the ICA, but application to other vascular regions should be performed with caution.


2006 ◽  
Vol 24 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Daryl R. Williams ◽  
L. Elaine Epperson ◽  
Weizhong Li ◽  
Margaret A. Hughes ◽  
Ruth Taylor ◽  
...  

Hibernation is a seasonally entrained and profound phenotypic transition to conserve energy in winter. It involves significant biochemical reprogramming, although our understanding of the underpinning molecular events is fragmentary and selective. We have conducted a large-scale gene expression screen of the golden-mantled ground squirrel, Spermophilus lateralis, to identify transcriptional responses associated specifically with the summer-winter transition and the torpid-arousal transition in winter. We used 112 cDNA microarrays comprising 12,288 probes that cover at least 5,109 genes. In liver, the profiles of torpid and active states in the winter were almost identical, although we identified 102 cDNAs that were differentially expressed between winter and summer, 90% of which were downregulated in the winter states. By contrast, in cardiac tissue, 59 and 115 cDNAs were elevated in interbout arousal and torpor, respectively, relative to the summer active condition, but only 7 were common to both winter states, and during arousal none was downregulated. In brain, 78 cDNAs were found to change in winter, 44 of which were upregulated. Thus transcriptional changes associated with hibernation are qualitatively modest and, since these changes are generally less than twofold, also quantitatively modest. Unbiased Gene Ontology profiling of the transcripts suggests a winter switch to β-oxidation of lipids in liver and heart, a reduction in metabolism of toxic compounds and the urea cycle in liver, and downregulated electron transport in the brain. We identified just one strongly winter-induced transcript common to all tissues, namely an RNA-binding protein, RBM3. This analysis clearly differentiates responses of the principal tissues, identifies a large number of new genes undergoing regulation, and broadens our understanding of affected cellular processes that, in part, account for the winter-adaptive hibernating phenotype.


2008 ◽  
Vol 294 (5) ◽  
pp. H2002-H2011 ◽  
Author(s):  
Karl H. Schuleri ◽  
Luciano C. Amado ◽  
Andrew J. Boyle ◽  
Marco Centola ◽  
Anastasios P. Saliaris ◽  
...  

The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controversial. Myocardial regeneration and neovascularization, which leads to increased tissue perfusion, are proposed mechanisms. Here we demonstrate that delivery of MSCs 3 days after MI increased tissue perfusion in a manner that preceded improved LV function in a porcine model. MI was induced in pigs by 60-min occlusion of the left anterior descending coronary artery, followed by reperfusion. Pigs were assigned to receive intramyocardial injection of allogeneic MSCs (200 million, ∼15 injections) ( n = 10), placebo ( n = 6), or no intervention ( n = 8). Resting myocardial blood flow (MBF) was serially assessed by first-pass perfusion magnetic resonance imaging (MRI) over an 8-wk period. Over the first week, resting MBF in the infarct area of MSC-treated pigs increased compared with placebo-injected and untreated animals [0.17 ± 0.03, 0.09 ± 0.01, and 0.08 ± 0.01, respectively, signal intensity ratio of MI to left ventricular blood pool (LVBP); P < 0.01 vs. placebo, P < 0.01 vs. nontreated]. In contrast, the signal intensity ratios of the three groups were indistinguishable at weeks 4 and 8. However, MSC-treated animals showed larger, more mature vessels and less apoptosis in the infarct zones and improved regional and global LV function at week 8. Together these findings suggest that an early increase in tissue perfusion precedes improvements in LV function and a reduction in apoptosis in MSC-treated hearts. Cardiac MRI-based measures of blood flow may be a useful tool to predict a successful myocardial regenerative process after MSC treatment.


2017 ◽  
Vol 114 (9) ◽  
pp. 2331-2336 ◽  
Author(s):  
Tak W. Mak ◽  
Ludger Hauck ◽  
Daniela Grothe ◽  
Filio Billia

The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP–mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed. Genome-wide annotation and pathway analyses of >5,000 differentially expressed transcripts identified many p53-regulated gene clusters. Correlative analyses identified >20 gene sets containing more than 1,000 genes relevant to cardiac architecture and function. These transcriptomic changes orchestrate cardiac architecture, excitation-contraction coupling, mitochondrial biogenesis, and oxidative phosphorylation capacity. Interestingly, the gene expression signature in p53-deficient hearts confers resistance to acute biomechanical stress. The data presented here demonstrate a role for p53, a previously unrecognized master regulator of the cardiac transcriptome. The complex contributions of p53 define a biological paradigm for the p53 regulator network in the heart under physiological conditions.


2021 ◽  
Vol 39 (3) ◽  
Author(s):  
SUELLEN CRISTINA DIAS EMIDIO ◽  
Laís Pereira Giovanini ◽  
Paula Rocco Gomes Lima ◽  
Julia Leme Gonçalves ◽  
Ana Railka De Souza Oliveira-Kumakura

Objective: To identify the nursing diagnoses of risk for decreased cardiac tissue perfusion and risk for activity intolerance and establish the association between the components of both diagnoses and the signs and symptoms of acute coronary syndromes. Materials and methods: Observational and associative study with 75 patients diagnosed with acute coronary syndrome in a Brazilian public hospital. Inferential statistics and multiple Poisson regression models were applied. Results: 84% of the patients showed risk for activity intolerance and 80% reported risk for decreased cardiac tissue perfusion. Risk factors were present in more than 50% of the sample. The diagnoses showed a high frequency in patients with acute coronary syndrome. Pharmacological agents, presence of comorbidities, and family and personal history were associated with the diagnoses. Absence of evidence of decreased cardiac tissue perfusion as dyspnea, radiation to shoulder and jaw, and pain time less than ten hours acted as protective factors. Conclusion: There is a high cardiovascular vulnerability of patients with acute coronary syndrome to the proposed nursing diagnoses. Therefore, we recommend further studies to determine the predictive power of the assessed risk diagnoses for those focusing on this health problem.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aritra Bhattacherjee ◽  
Mohamed Nadhir Djekidel ◽  
Renchao Chen ◽  
Wenqiang Chen ◽  
Luis M. Tuesta ◽  
...  

Abstract Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors. Yet, the specific transcriptional programs in each neuron subtype remain unknown. Using single-cell RNA sequencing (scRNA-seq), here we comprehensively classify all unique cell subtypes in the PFC. We analyze transcriptional dynamics of each cell subtype under a naturally adaptive and an induced condition. Adaptive changes during adolescence (between P21 and P60), a highly dynamic phase of postnatal neuroplasticity, profoundly impacted transcription in each neuron subtype, including cell type-specific regulation of genes implicated in major neuropsychiatric disorders. On the other hand, an induced plasticity evoked by chronic cocaine addiction resulted in progressive transcriptional changes in multiple neuron subtypes and became most pronounced upon prolonged drug withdrawal. Our findings lay a foundation for understanding cell type-specific postnatal transcriptional dynamics under normal PFC function and in neuropsychiatric disease states.


2019 ◽  
Vol 71 (6) ◽  
pp. 1899-1914
Author(s):  
Zhi-Gang Wu ◽  
Wu Jiang ◽  
Zheng-Ming Tao ◽  
Xiao-Jun Pan ◽  
Wen-Hui Yu ◽  
...  

Abstract In yam (Dioscorea spp) species, bulbils at leaf axils are the most striking species-specific axillary structure and exhibit important ecological niches. Genetic regulation underlying bulbil growth remains largely unclear so far. Here, we characterize yam (Dioscorea alata L.) bulbil development using histological analysis, and perform full transcriptional profiling on key developmental stages together with phytohormone analyses. Using the stage-specific scoring algorithm, we have identified 3451 stage-specifically expressed genes that exhibit a tight link between major transcriptional changes and stages. Co-expressed gene clusters revealed an obvious over-representation of genes associated with cell division and expansion at the initiation stage of bulbils (T1). Transcriptional changes of hormone-related genes highly coincided with hormone levels, indicating that bulbil initiation and growth are coordinately controlled by multiple phytohormones. In particular, localized auxin is transiently required to trigger bulbil initiation, and be further depleted or exported from bulbils to promote growth by up-regulation of genes involved in auxinconjugation and efflux. The sharp increase in supply of sucrose and an enhanced trehalose-6-phophate pathway at T1 were observed, suggesting that sucrose probably functions as a key signal and promotes bulbil initiation. Analysis of the expression of transcription factors (TFs) predicated 149 TFs as stage-specifically expressed; several T1-specific TFs (from Aux/IAA, E2F, MYB, and bHLH families) have been shown to play key roles in triggering bulbil formation. Together, our work provides a crucial angle for in-depth understanding of the molecular programs underlying yam’s unique bulbil development processes. Stage-specific gene sets can be queried to obtain key candidates regulating bulbil growth, serving as valuable resources for further functional research.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Qince Li ◽  
KahYong Goh ◽  
Wei Kong ◽  
Ruby R Ni ◽  
Vladimir Fast ◽  
...  

Optogenetics is an emerging technology allowing remote and precise control of cell activity in living tissues. Despite its rapid advancements, application of this innovative technology to cardiovascular research is still limited, in part due to shortage of optogenetic cardiac tissue models and compatible imaging methods. The present study aimed to develop an optogenetic culture model using neonatal rat ventricular myocytes (NRVM) expressing light-gated Channelrhodopsin-2 (ChR2) and characterize activation spread during optical stimulation using optical mapping of membrane potential (Vm). Primary NVRM cultures were infected with lentivirus containing ChR2 gene. Cultures were paced electrically or optically with pulses of blue (470 nm) LED light. Activation spread was simultaneously mapped using Vm-sensitive dye (RH-237) and a photodiode mapping system. Results showed that ChR2 could be readily transduced to NRVMs by the lentiviral method; however, high-level ChR2 expression was associated with substantial cell toxicity. Lower ChR2 expression, achieved by administration of bromodeoxyuridine, had minor effects on cell morphology and function while allowing optical pacing at frequencies of 0.5-3 Hz. Simultaneous Vm mapping showed that conduction velocity, APD80, and dV/dtmax were similar in optogenetic and control cultures. Finally, the optogenetic cultures could be optically paced at multiple sites, leading to significantly reduced overall activation time. In summary, we demonstrated that ChR2 expression can cause cell toxicity in NRVM cultures but the toxicity can be mitigated allowing optical pacing and simultaneous optical activation mapping without significant impairment of electrophysiological function. This optogenetic cardiac culture model expands the availability of optogenetic tools for cardiac research.


2015 ◽  
Vol 27 (3) ◽  
pp. 175-180 ◽  
Author(s):  
Vinicius Batista Santos ◽  
Álvaro Nagib Atallah ◽  
Camila Takáo Lopes ◽  
Juliana de Lima Lopes ◽  
Alba Lúcia Bottura Leite de Barros

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