Biology subjects

Yang, A.

Publications and source records attributed to Yang, A..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Transfer RNA acetylation regulates in vivo mammalian stress signaling

Transfer RNA (tRNA) modifications are crucial for protein synthesis, but their position-specific physiological roles remain poorly understood. Here we investigate the impact of N4-acetylcytidine (ac4C), a highly conserved tRNA modification, using a Thumpd1 knockout mouse model. We find that loss of Thumpd1-dependent tRNA acetylation leads to reduced levels of tRNALeu, increased ribosome stalling, and activation of eIF2 phosphorylation. Thumpd1 knockout mice exhibit growth defects and sterility. Remarkably, concurrent knockout of Thumpd1 and the stress-sensing kinase Gcn2 causes penetrant postnatal lethality, indicating a critical genetic interaction. Our findings demonstrate that a modification restricted to a single position within type II cytosolic tRNAs can regulate ribosome-mediated stress signaling in mammalian organisms, with implications for our understanding of translation control as well as therapeutic interventions.

developmental biology↗

bioRxiv2024

Maternal Immunoglobulin A regulates the development of the neonatal microbiota and intestinal microbiota-specific CD4+ T cell responses

Breast milk is a complex mixture of nutrients and bioactives that promote infant development and decrease the incidence of chronic inflammatory disease. We investigated the role of one milk-derived bioactive, Immunoglobulin A (IgA) on the developing small intestinal microbiota and immune system. We demonstrate that early in life, milk-derived IgA suppressed colonization of the small intestine by Enterobacteriaceae and regulated the maturation of the small intestinal epithelium and the development of intestinal IL-17-producing CD4+ T cells. Enterobacteriaceae- specific CD4+ T cells, induced in the first weeks of life in the absence of milk-derived IgA, persisted in the intestine as memory T cells that can contribute to inflammatory disease later in life. Our study suggests that milk-derived IgA shapes mucosal immunity by regulating the neonatal microbiota thus preventing the development of long-lived intestinal microbiota-specific T cells.

immunology↗

bioRxiv2024

High refresh rate display for natural monocular viewing in AOSLO psychophysics experiments

By combining an external display operating at 360 frames per second with an Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) for human foveal imaging, we demonstrate color stimulus delivery at high spatial and temporal resolution in AOSLO psychophysics experiments. A custom pupil relay enables viewing of the stimulus through a 3-mm effective pupil diameter and provides refractive error correction from -8 to +4 diopters. Performance of the assembled and aligned pupil relay was validated by measuring the wavefront error across the field of view and correction range, and the as-built Strehl ratio was 0.64 or better. High-acuity stimuli were rendered on the external display and imaged through the pupil relay to demonstrate that spatial frequencies up to 54 cycles per degree, corresponding to 20/11 visual acuity, are resolved. The completed external display was then used to render fixation markers across the field of view of the monitor, and a continuous retinal montage spanning 9.4 by 5.4 degrees of visual angle was acquired with the AOSLO. We conducted eye-tracking experiments during free-viewing and high-acuity tasks with polychromatic images presented on the external display. Sub-arcminute eye position uncertainty was achieved, enabling precise localization of the line of sight on the monitor while simultaneously imaging the fine structure of the human central fovea. This high refresh rate display overcomes the temporal, spectral, and field of view limitations of AOSLO-based stimulus presentation, enabling natural monocular viewing of stimuli in psychophysics experiments conducted with AOSLO.

bioengineering↗

bioRxiv2024

Cortical Dynamics during Contour Integration

Integrating visual elements into contours is important for object recognition. Previous studies emphasized the role that the primary visual cortex (V1) plays in this process. However, recent evidence suggests that contour integration relies on the coordination of hierarchical substrates of cortical regions through recurrent connections. Many previous studies presented the contour at the same onset-time as the trial, which caused the subsequent neural imaging data to incorporate both visual evocation and contour integration activities, and thus confounding the two. In this study, we varied both the contour onset-time and contour fidelity and used EEG to examine the cortical activities under these conditions. Our results suggest that the temporal N300 represents the grouping and integration of visual elements into contours. Before this signature, we observed interhemispheric connections between lateral frontal and posterior parietal regions that were contingent on the contour location and peaked at around 150ms after contour appearance. Also, the magnitudes of connections between medial frontal and superior parietal regions were dependent on the timing of contour onset and peaked at around 250ms after contour onset. These activities appear to be related to the bottom-up and top-down attentional processing during contour integration, respectively, and shed light on how these processes cooperate dynamically during contour integration.

neuroscience↗

bioRxiv2024

Silicone Wire Embolization-induced Acute Retinal Artery Ischemia and Reperfusion Model in Mouse: Gene Expression Provide Insight into Pathological Processes

Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60-minutes of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

neuroscience↗

bioRxiv2024

Proteome trade-off between primary and secondary metabolism shapes acid stress induced bacterial exopolysaccharide production

The exopolysaccharide (EPS) produced by Lactiplantibacillus plantarum is a high-value bioproduct in food and health industries, and its biosynthesis has been found as a secondary metabolic pathway to mediate acid stress. To quantitatively investigate acid stress response in L. plantarum and model EPS production, this study measured metabolomics, proteomics and growth data for L. plantarum HMX2 cultured at 4 different pH values. The growth and metabolomics data showed that under acid stress, the EPS production flux was evidently enhanced while the glycolysis and cellular growth were inhibited. The following proteomic analysis found that EPS biosynthetic proteins were significantly up-regulated under acid stress and pinpointed Fur as the most probable transcriptional factor controlling EPS biosynthesis in L. plantarum. Furthermore, we identified a proteome trade-off between primary metabolism and EPS biosynthesis, which were then mechanistically depicted by a regulatory proteome constrained flux balance analysis (RPCFBA) model. As the first metabolic model that can simulate secondary metabolism, the RPCFBA model demonstrated good accuracy in predicting growth rates and EPS production fluxes of L. plantarum HMX2, validated by experimental data. The in-silico perturbation on carbon sources further showed the potential of applying the presented modeling framework to the design and control of microbial secondary metabolism.

systems biology↗

bioRxiv2024

Regional Glymphatic Dysfunction is linked to Spinocerebellar Ataxia Type 3 pathophysiology

Spinocerebellar ataxia type 3 (SCA3) involves neuroinflammation and imbalance between production and clearance of proteins which affects the glymphatic system, the lymphatic-like, fluid-transport system in the brain. However, it is unclear whether SCA3 is related to impairments in glymphatic function. Using multimodal imaging data, 34 SCA3 patients and 36 age-, sex- and educational matched healthy controls (HCs) were compared using multiple glymphatic measurements, including choroid plexus (CP) and cerebrospinal fluid (CSF) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling relationship between blood-oxygen-level-dependent signals and CSF flow (BOLD-CSF coupling). Then, we evaluated regional glymphatic function by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, posterior, and cerebellum regions, thereby identifying the spatial variation of glymphatic function in the two groups. We demonstrated that compared with HCs, larger CP and CSF volumes were found in SCA3 patients. More importantly, for DTI-ALPS index and BOLD-CSF coupling, these surrogate markers for glymphatic clearance were weaker in SCA3 patients. Furthermore, altered regional glymphatic functions were most prominent in midbrain, cerebellum and middle regions. Crucially, the altered midbrain, cerebellum, middle and global glymphatic functions were accompanied by the severity of ataxia and other SCA3 symptoms. Similar to other neurodegenerative disorders, the association between multiple glymphatic indexes and SCA3 symptoms suggested that waste clearance is disrupted in SCA3 patients, which shed light on the pathogenesis of this disease from a glymphatic lens. Our findings highlighted the dysregulated glymphatic function as a novel diagnostic marker for SCA3.

neuroscience↗

bioRxiv2024

GLP1R agonists activate human POMC neurons

Drugs like semaglutide (a.k.a. Ozempic/Wegovy) that activate the glucagon-like peptide-1 receptor (GLP-1R) are a promising therapy for obesity and type 2 diabetes (T2D). Animal studies suggest that these drugs likely function by stimulating GLP-1R on appetite-suppressing neuron populations in the brain, but it is still unclear how they act to reduce food intake in humans. We therefore generated appetite-regulatory hypothalamic neurons from human pluripotent stem cells (hPSCs) to study their responses to GLP-1R agonists by calcium imaging and electrophysiology. We found that hPSC-derived proopiomelanocortin (POMC) and other hypothalamic neuron subtypes expressed GLP1R mRNA, and many of these neurons robustly responded to GLP-1R agonists by membrane depolarization, increased action potential firing, and extracellular calcium influx that persisted long after agonist withdrawal. The observed GLP-1R-induced response was likely mediated by the activation of PKA and L-type calcium channels, and led to significant changes in gene expression. These findings provide mechanistic insight into how GLP-1R agonists may suppress appetite in humans.

neuroscience↗

bioRxiv2024

Whole-genome resequencing revealed the Origin and Domestication of Chinese Domestic Rabbits

The evolutionary and genetic origins of Chinese indigenous rabbits (Oryctolagus cuniculus) remain largely unclear, despite being among the most recently domesticated animals. We sequenced the whole genomes of 142 individual rabbits and collected 25 resequencing accessions from the NCBI, representing six Chinese indigenous breeds, three other domesticated breeds (serving as a bridge between European wild-type and Chinese domestic populations), and two wild rabbit populations from the Iberian Peninsula and Southern France. Population and demographic analyses suggest that Chinese domestic rabbits are most likely descendants of O. c. cuniculus, native to France 800-1500 years ago. These rabbits likely first arrived in the southeast coastal areas of China through trade before spreading to inland regions. Additionally, there may be other origins for Chinese domestic rabbits. We observed considerable variation in the genetic makeup of maternal ancestry between Chinese domestic rabbits and European wild populations, with Chinese rabbits possessing unique mitochondrial haplotypes. Our analysis also highlights selective sweeps on genes affecting brain and neuronal development, which may have been under strong positive selection during domestication; genes related to starch digestion and fat metabolism, suggesting an evolutionary adaptation to digest high-starch diets; and the white coat phenotype in rabbits, resulting from selection at the melanogenesis-associated transcription factor locus. Overall, our data provide comprehensive insights into the origin and domestication of rabbits and lay the foundation for genome-based breeding.

evolutionary biology↗

bioRxiv2024

Differential seasonal effects of ephemeral legumes in response to moisture-nitrogen coupling in the deserts of northwestern China

Desert ecosystems are ecosystems limited by both nitrogen and moisture, while legumes, as an important source of nitrogen in desert ecosystems, are extremely sensitive to respond to moisture and nitrogen changes. In order to reveal the growth and physiological metabolic processes of desert legumes in response to moisture and nitrogen changes. In this study, two dominant ephemeral legumes, Trigonella arcuata C. A. Mey. and Astragalus arpilobus Kar. & Kir. were selected from the Gurbantunggut Desert through a controlled experiment in greenhouse pots: four moisture treatment levels were established: W1(soil moisture content of 5 %), W2(soil moisture content of 7 %), W3( 9 % soil moisture content), W4(11 % soil moisture content) and three N treatment levels: N1(0 mmol/L 15NH4 15NO3), N2(18 mmol/L 15NH4 15NO3), N3(72 mmol/L 15NH4 15NO3), and we conducted a 15N tracking experiment for the pot treatments throughout the growing season. The results showed that: (1) moisture and nitrogen treatments had similar patterns on above-ground and below-ground as well as total fresh weight, plant height and basal diameter, Chla, Chlb and Chla+b of the two legumes, all of which were greatest in the W3N3 treatment and smallest in the W4N1 treatment, but the growth characteristics and chlorophyll parameters had cumulative differences over the growing season. (2) When subjected to severe moisture and nitrogen stresses, the 2 plants would increase the physiological levels of stress tolerance in vivo to enhance cellular resistance, with the osmoregulatory substance content being the most sensitive in response to moisture, and the cell membrane and antioxidant enzyme systems being the most sensitive in response to nitrogen stress. (3) The adaptive characteristics of physiological metabolic processes in plants to seasonal changes, in which growth characteristics, cell membrane and antioxidant enzyme content accumulation showed: rapid growth period < maximum biomass period, while chlorophyll content and osmoregulatory substance content accumulation content accumulation showed: rapid growth period > maximum biomass period. In general, drought can hinder nitrogen uptake and transport, while sufficient moisture can accelerate the nutrient metabolism process of plants, and there is a nutrient dilution effect once the moisture is in excess, but in the nitrogen starvation state, the moisture factor has almost no effect on plants, therefore, the moisture-nitrogen coupling effect is more reflective of the physiological response characteristics of the plants when they encountered the adversity stress, and the degree of accumulation is different in different growing seasons, and the plants in the The differences in different growing seasons reflect the changes in photosynthetic intensity and energy demand.

ecology↗

bioRxiv2024

Mechanical confinement induces ferroptosis through mitochondrial dysfunction

Cells exist in highly crowded environments where they are exposed to fluctuating mechanical forces arising from surrounding cells and the extracellular matrix microenvironment. In these settings, external forces are transmitted to intracellular organelles including the nucleus. While cells can survive confinement, extended duration of confinement or confinement in settings where cells are unable to escape, can result in cell death. How cells sense and respond to prolonged confinement to trigger cell death remains unclear. Here, we demonstrate that nuclear deformation generated by axial confinement triggers the programmed cell death pathway - ferroptosis. We show that axial confinement results in Drp1-dependent mitochondrial fragmentation and cPLA2 translocation to mitochondria, where Drp1 undergoes acute phase separation. Ensuing mitochondrial ROS accumulation and arachidonic acid production concertedly leads to lipid peroxidation evoking ferroptosis. Finally, of clinical relevance, we find that in human osteoarthritis tissue cPLA2 exhibits mitochondrial localization and high ROS levels. Together, our findings unveil a pivotal role for Drp1 and cPLA2 in linking mechanical confinement with mitochondrial dysfunction resulting in ferroptosis, which sheds new light on a mechanical mechanism of pathophysiology in osteoarthritis.

cell biology↗

bioRxiv2024

A POLR3B-variant reveals a Pol III transcriptome response dependent on La protein/SSB

RNA polymerase III (Pol III, POLR3) synthesizes tRNAs and other small non-coding RNAs. Human POLR3 pathogenic variants cause a range of developmental disorders, recapitulated in part by mouse models, yet some aspects of POLR3 deficiency have not been explored. We characterized a human POLR3B:c.1625A>G;p.(Asn542Ser) disease variant that was found to cause mis-splicing of POLR3B. Genome-edited POLR3B1625A>G HEK293 cells acquired the mis-splicing with decreases in multiple POLR3 subunits and TFIIIB, although display auto-upregulation of the Pol III termination-reinitiation subunit POLR3E. La protein was increased relative to its abundant pre-tRNA ligands which bind via their U(n)U-3-termini. Assays for cellular transcription revealed greater deficiencies for tRNA genes bearing terminators comprised of 4Ts than of [≥]5Ts. La-knockdown decreased Pol III ncRNA expression unlinked to RNA stability. Consistent with these effects, small-RNAseq showed that POLR3B1625A>Gand patient fibroblasts express more tRNA fragments (tRFs) derived from pre-tRNA 3-trailers (tRF-1) than from mature-tRFs, and higher levels of multiple miRNAs, relative to control cells. The data indicate that decreased levels of Pol III transcripts can lead to functional excess of La protein which reshapes small ncRNA profiles revealing new depth in the Pol III system. Finally, patient cell RNA analysis uncovered a strategy for tRF-1/tRF-3 as POLR3-deficiency biomarkers.

molecular biology↗

bioRxiv2024

Reprogramming of 3D genome structure underlying HSPC development in zebrafish

Development of hematopoietic stem and progenitor cells (HSPC) is a multi-staged complex process that conserved between zebrafish and mammals; however, the mechanism underlying HSPC development is not fully understood. Chromatin conformation plays important roles in transcriptional regulation and cell fate decision, its dynamic and role in HSPC development is poorly investigated. Here, we performed chromatin structure and multi-omics dissection across different stages of HSPC developmental trajectory in zebrafish. Chromatin organization of zebrafish HSPC resemble mammalian cells with similar hierarchical structure and characteristics. We revealed the multi-scale reorganization of 3D genome and its influence on transcriptional regulation and transition of cell function during HSPC development. Nascent HSPC is featured by loose conformation with obscure structure at all layers. Notably, PU.1 was identified as a potential factor mediating formation of promoter-involved loops and regulating gene expression as well as HSPC function. Our results provided a global view of chromatin structure dynamics associated with development of zebrafish HSPC and discovered key transcription factor involved in HSPC chromatin interactions, which will provide new insights into the epigenetic regulatory mechanisms underlying vertebrate HSPC fate decision.

genomics↗

bioRxiv2023

Variant Graph Craft (VGC): A Comprehensive Tool for Analyzing Genetic Variation and Identifying Disease-Causing Variants.

The Variant Call Format (VCF) file is providing a structured and comprehensive text file that contains essential information about variant positions in the genome, as well as other critical details, such as alleles, genotype calls, and quality scores. Due to its rich data and format, the VCF file has become an increasingly popular resource for researchers and clinicians alike, enabling them to interpret and understand genomic variation data. However, analyzing and visualizing these files poses significant challenges, demanding access to diverse resources and a robust set of features for in-depth exploration. We introduce Variant Graph Craft (VGC), a VCF file visualization and analysis tool offering a wide range of features for exploring genetic variations, including extraction of variant data, intuitive visualization of variants, and the provision of a graphical representation of samples, complete with genotype information. Furthermore, VGC seamlessly integrates with external resources to offer valuable insights into gene function and variant frequencies in sample data. VGC offers gene function and pathway information from Molecular Signatures Database (MSigDB) for GO terms, as well as KEGG, Biocarta, Pathway Interaction Database, and Reactome. Additionally, the tool also provides a dynamic link to gnomAD for variant information, and includes ClinVar data for pathogenic variant information. VGC operates locally, assuring users of data security and privacy by eliminating the need for cloud-based VCF uploads. It supports the Human Genome Assembly Hg37, ensuring compatibility with a wide range of data sets. With its versatility, VGC accommodates various approaches exploring genetic variation data, and can be tailored to the specific needs of the user by using optional phenotype input data. In conclusion, VGC is a useful resource for exploring genetic variation in a secure and user-friendly environment. With its user-tailored set of features, this tool enables researchers and clinicians to easily explore and understand genomic variation data in a comprehensive and accessible manner. From identifying specific genetic mutations to analyzing patterns of variation across the genome, the VCF file visualization and analysis tool is an essential tool for those working in the field of genomics. VGC is freely available at https://sites.brown.edu/gmilab/variantgraphcraft/

bioinformatics↗

bioRxiv2023

Not dasycladalean alga, but an Odyssey of the earliest Phanerozoic animal reef-builders

The compacted macrofossil Protomelission? sp. from the early Cambrian Xiaoshiba Lagerstatte was recently ascribed to early dasycladalean green algae and used to disprove the bryozoan affinity of coeval phosphatized microfossils, which made the puzzling question whether the bryozoans originated in early Cambrian pending again. Our new analyses of multiple specimens which are conspecific with Protomelission? from the Chengjiang Lagerstatte indicate that they are not dasycladaleans but one of the three groups of archaeocyath-like sponges that atypically inhabited siliciclastic substrates. All the archaeocyath-like fossils share the same preservation mode and exhibit archaeocyath-type external skeletal features. Particularly, the Protomellision?-like fossils preserve structures indicative of archaeocyath aquiferous system and ontogeny. They represent the first recognized one-walled archaeocyath sponges in South China and evidence the niche expansion of archaeocyaths on their way of global radiation from Siberia, 518 million years ago. The origin of the bryozoans remains a mystery.

paleontology↗

bioRxiv2023

Running to remember: The effects of exercise on perineuronal nets, microglia, and hippocampal angiogenesis in female and male mice

Exercise is accepted as a positive health behaviour; however, the mechanisms of exercise on neuroprotection and cognitive health are not completely understood. The purpose of this study was to explore the neurobiological benefits of chronic treadmill exercise in female and male mice through its role in microglial content and morphology, cerebral vascularization, and perineuronal net (PNN) expression. We further examined how these neurobiological changes relate to spatial memory outcomes. Adult mice were assigned to a sedentary or treadmill exercise group for eight weeks. During the final week, all mice were trained on a spatial memory task (Barnes maze) and brains were collected for immunohistochemistry. Exercised mice made fewer errors than sedentary mice during the first two days of training and probe trial. Females, regardless of exercise training, made fewer errors during Barnes maze training and demonstrated a greater frequency of spatial strategy use compared to males. Exercised mice, regardless of sex, had fewer PNNs in the dentate gyrus of the hippocampus compared to sedentary controls. The number of PNNs in the dorsal dentate gyrus was positively correlated with total errors during training. During the probe, greater errors correlated with more PNNs among the exercised group only. Microglia count and cerebral vascularization were not affected by exercise, although proportions of microglia type (ameboid, stout/thick, and thick/thin) were regulated by exercise in the ventral dentate gyrus. We conclude that exercise decreases PNNs in the dentate gyrus in both sexes and this may be related to better spatial learning and memory.

neuroscience↗

bioRxiv2023

Systematic elucidation of independently modulated genes in Lactobacillus plantarum reveals a trade-off between secondary and primary metabolism

Lactobacillus plantarum is a probiotic bacteria widely used in food and health industries, but its gene regulatory information is limited in existing databases, which impedes the research of its physiology and its applications. To obtain a better understanding of the transcriptional regulatory network of L. plantarum, independent component analysis (ICA) of its transcriptomes was used to derive 45 sets of independently modulated genes (iModulons). Those iModulons were annotated for associated transcription factors (TFs) and functional pathways, and active iModulons in response to different growth conditions were identified and characterized in detail. Eventually, the analysis of iModulon activities reveals a trade-off between regulatory activities of secondary and primary metabolism in L. plantarum.

systems biology↗

bioRxiv2023

Vicious cycle of hemodynamic perturbation and endothelial injury in development and progression of pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) is a devastating disease caused by loss of effective lung microvasculature for which there is no curative treatment. Evidence from preclinical models and human disease-causing genetic mutations point to endothelial cell (EC) injury and apoptosis as a central trigger for the initiation of PAH. However, how EC apoptosis leads to pulmonary hypertension (PH) and complex arteriolar remodeling is uncertain. MethodsRats were subjected to SU5416-hypoxia (SUHx) and EC apoptosis, pulmonary vascular remodeling and arterial volume was assessed by immunohistochemistry, histology and microCT, respectively. Left pulmonary artery banding (LPAB) was performed, either 1 week before (prevention) or 5 weeks after SU injection (reversal), to study the effect of hemodynamic offloading. ResultsIn the SUHx model, EC apoptosis was markedly increased as early as 3 days post-SU, persisting through PAH development, and this was associated with a profound arterial pruning with reduction in lung arterial volume ([~]80%). LPAB abrogated lung EC apoptosis in the banded left lung and prevented as well as reversed arteriolar pruning. Moreover, in the reversal protocol, removal of the band at 10 weeks resulted in improvement in pulmonary hemodynamics and RV function at 13 weeks. ConclusionThese data demonstrate that perturbed hemodynamic factors triggered by lung microvascular arteriolar loss play a requisite role in perpetuating endothelial injury in experimental PAH, leading to persistent arterial EC injury and disease progression. Importantly, vascular loss, arterial remodeling and PH are reversible once the cycle of perturbed hemodynamics and EC injury is broken by unilateral lung banding.

physiology↗