bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Open‐label Study to Evaluate the Effect of 5,000 IU of Vitamin D3 Softgel on Serum 25‐hydroxyvitamin D Levels among Healthy Adults
Authors: Hirsh Steven , Huber Luke , Schmid Kira , Woolger Judith , Joyal Steven 
Published: June 2021

BackgroundThere has been little research performed to determine the most effective vehicle, from a bioavailability perspective, for vitamin D supplementation. It has been observed that further studies are needed to compare the bioavailability from the use of different vehicles (eg, powders, oils, and ethanol).ObjectiveTo assess the effect of a 5,000 IU vitamin D3 lipid‐based softgel formulation on serum 25‐hydroxyvitamin D levels in healthy male and female subjects already taking a daily 5,000 IU vitamin D3 encapsulated powder formulation for at least 3 months.MethodsAfter discontinuing their vitamin D3 capsules, 16 qualified participants were dispensed and instructed to take a lipid‐based softgel formulation containing 5,000 IU vitamin D3 for 60 days. Assessments of 25‐hydroxyvitamin D level were conducted at baseline (prior to vitamin D3 softgel ingestion), Day 30, and Day 60.ResultsFifteen participants completed the study with no serious adverse events reported. 25‐hydroxyvitamin D levels increased an average of 7.34 ng/mL (16%) by day 30 and 13.1 ng/mL (28.5%) by day 60 compared to baseline. The mean changes from baseline to days 30 and 60 were statistically significant.ConclusionThe lipid‐based softgel formulation containing 5,000 IU of vitamin D3 taken daily for 60 days was associated with a statistically significant increase in 25‐hydroxyvitamin D levels among healthy adults subsequent to use of 5,000 IU vitamin D3 capsules for 3 months or more. Hence, our findings provide a rationale for further studies investigating the most effective vehicle for vitamin D3 supplementation.
The combination of docosahexaenoic acid (DHA) and regorafenib synergistically inhibits colon cancer cell growth.
Authors: Cai Xiaokun , Zhang Guodong , Xiao Hang 
Published: June 2021

Utilization of different anticancer agents in combination to produce enhanced inhibitory effects on carcinogenesis is a promising approach to improve anticancer efficacy and reduce potential side‐effects. In this study, we investigated the combination effects between DHA and regorafenib, a potent chemotherapeutic drug for advanced colorectal cancer, on human colon cancer cells. Cell viability assay and colony formation assay demonstrated that the combination of DHA and regorafenib had much stronger inhibitory effects on the cancer cells in comparison to the treatments with DHA or regorafenib alone. These enhanced effects were confirmed to be synergistic by isobologram analysis. Cell cycle and apoptosis assay showed significant G1 phase cell cycle arrest and extensive apoptosis induced by the combination treatment. Results from Western blotting indicated that the inhibitory effects of the combination treatment was associated with increased levels of cleaved caspase 3, cleaved PARP and P21. Overall, our results provide a basis for using DHA and regorafenib in combination for the inhibition of colon cancer. The enhanced anticancer effects by the combination may reduce the required dose of regorafenib for efficacy, which may lower the unwanted side‐effects of regorafenib such as hypertension.This study was supported in part by the Armstrong Fund for Science from University of Massachusetts Amherst.
In Vivo Neuroprotective Effects of Cinnamon Bioactive Compounds in C. elegans and D. melanogaster
Authors: Stavinoha Rebecca , Gomada Yuki , Jamison Brandon , Vattem Dhiraj 
Published: June 2021

We previously reported that polar fractions of cinnamon may have therapeutic potential in Alzheimer's disease (AD) and Parkinson's disease (PD). The objective here was to evaluate the in vivo neuroprotective effects of polar bioactive compounds (10‐25 mg/ml of Sodium Benzoate, Cinnamic Acid, Cinnamaldehyde, Cinnamyl Acetate, Ethyl Cinnamate and Procyanidin B1) on experimentally induced neurodegeneration in C. elegans and D. melanogaster. For AD, time to thermally induced Aβ1–42 aggregation mediated paralysis was evaluated in transgenic C. elegans (CL4176). For PD, MPP+ induced neurodegeneration was qualtified by loss in motility and degradation of GFP signal in wild type and transgenic C. elegans. In drosophila, neurodegeneration was induced via the UAS/GAL4 tissue‐specific expression system and neurotoxicity was induced via exposure to rotenone (0.5 M ) and scored for locomotion, and geotaxis. Results suggest that treatment with bioactive compounds caused statistically significant (p < 0.05) amelioration (12‐30%) in markers of neurodegeneration and neurotoxicity both C. elegans and D. melanogaster.Grant Funding Source: VRDÜR Foundation
Evaluation of the Anti‐Inflammatory and Analgesic Activities of Leaf‐Extracts of Sterculia tragacantha in Rats
Authors: Abatan Matthew , Mogbojuri Olufunke 
Published: June 2021

Pilot toxicity studies using 200, 1000 and 3000 mg/kg doses of the aqueous extract of Sterculia tragacantha in albino rats did not produce significant (P< 0.05) adverse effects on haematological and biochemical parameters. Doses of the chloroform extract at 100 and 200 mg/kg caused inhibition of increase in paw volume at 1 hr (9.9%), 2 hrs (10.7%) and 3hrs (14.0%); whereas the 200mg/kg dose caused 1 hr (13.4), 2 hrs (16.4) and 3hrs (20.6%) inhibition in paw oedema.Evaluation of the n‐hexane extract of S. tragacantha produced 53.9 and 68.8% inhibition of writhing pain at 100 and 200 mag/kg doses respectively; the 100 and 200 mg/kg doses of the chloroform extract also produced 50 and 79.3% inhibition writhing pain respectively. Pooled chromatographic fractions of the chloroform extract with common Rf gave crystals which when tested at 25mg/kg dose gave a 35.4% inhibition of inflammation whereas the same dose produced 79.1% inhibition of writhing pain.Gas chromatographic mass spectrum analysis of the chloroform extract revealed the bioactive compounds to be n‐hexadecanoic acid, 9‐octadecanoic acid and n‐triacontane.It is concluded that the chloroform extract of S. tragacantha possesses anti‐inflammatory and analgesic properties which may account for the medicinal use.
Endothelial Dysfunction in DOCA‐salt Hypertensive Mice: A Role for nNOS‐derived Hydrogen Peroxide
Authors: Silva Grazielle , da Silva Josiane , Diniz Thiago , Lemos Virginia , Cortes Steyner 
Published: June 2021

Aimsinvestigated the involvement of neuronal nitric oxide synthase (nNOS) and H2O2 in the impaired endothelium‐dependent vasodilatation of mesenteric arteries from DOCA‐salt hypertensive mice (DOCA‐salt).Methods and resultsMyograph studies were used to investigate the endothelium‐dependent vasodilator effect of acetylcholine (ACh), the protein expression by Western blot, H2O2 formation by selective carbon microsensors permeable membrane and the protein localization in the endothelial layer of mesenteric arteries by immunofluorescence approved by ethics committee (protocol 227/08).The vasodilator effect of ACh is strongly impaired in mesenteric arteries from DOCA‐salt (SBP 180± 5 mmHg, Emax 51±2.3%) versus Sham (SBP 128±4 mmHg, Emax 99±1.2%). Nonselective inhibition of NOS strongly reduced the effect of ACh in both DOCA‐salt and Sham mice. Selective inhibition of nNOS and catalase induced a higher reduction in the effect of ACh in Sham than in DOCA‐salt. Production of H2O2 induced by ACh was significantly smaller in vessels from DOCA‐salt and it was blunted after the inhibition of nNOS. The expression of both eNOS and nNOS were significantly smaller in DOCA‐salt, while the phosphorylation of their inhibitory site was increased. The presence of nNOS was confirmed in the endothelial layer of mesenteric arteries from both Sham and DOCA‐salt.ConclusionA reduction in nNOS‐derived H2O2 production in DOCA/salt hypertensive mice partially contributes to endothelial dysfunction. This opens a new perspective for the understanding of the endothelial dysfunction in hypertension.Financial support: CNPq
Different Responses in CX3CL1/CX3CR1 and TNF‐α/TNFRSF1A Signaling Pathways to Aspirin in Human Umbilical Vein Endothelial Cells (HUVECs)
Authors: Szukiewicz Dariusz , Stangret Aleksandra 
Published: June 2021

Antiprostaglandin and antiplatelet actions of aspirin related to non‐equal and irreversible inhibition of cyclooxygenases (COX1, COX2) are widely known. COX‐independent antiinflammatory effects of aspirin were also reported. Acting as the nuclear factor‐kB (NF‐kB)inhibitor on endothelial cells, aspirin may modulate chemokine fractalkine (CX3CL1) signaling through its sole receptor CX3CR1. Thus, aspirin may reveal the opposite effect to TNF‐α, a strong inducer of CX3CL1/CX3CR1 signaling. We examined the effects of aspirin on CX3CL1 and TNF‐α production, as well as CX3CR1 and TNFRSF1A expression. HUVECs were isolated after normal term pregnancies (N = 24) and cultured in vitro. The cultures were exposed to aspirin (dose range: 1.0 – 6.0 mM) during the 7 day period. The mean concentrations of CX3CL1 and TNF‐α in the culture media supernatants were assessed at predefined time points by ELISA. After termination of the cultures, CX3CR1 and TNFRSF1A were immunostained in formalin fixed and paraffin embedded sections. To estimate the mean expression of these receptors, quantitative immunohistochemistry was applied. Aspirin significantly (p < 0.05) reduced production of CX3CL1, and the mean decline in CX3CL1 production was inversely proportional to the significantly (p < 0.05) augmented expression of CX3CR1. An inhibition of TNF‐α synthesis in HUVECs in response to aspirin treatment was also reported. There were no signs indicating upregulation of TNFRSF1A. Since autoregulatory relationships between CX3CL1 and CX3CR1 were proposed, overexpression of CX3CR1 observed in aspirin‐treated HUVECs may be a form of compensatory mechanism.WUM grant: 2M2‐N‐14
Cod Liver Oil Supplementation Effects on 2,3‐ Diphosphoglyceric Acid Blood Levels in Atherogenic Rabbits
Authors: Beard Elizabeth , Michals Edward 
Published: June 2021

2,3 Diphosphoglyceric Acid (2,3‐DPG) promotes release of oxygen from hemoglobin in the blood of higher animals, and may reduce atherogenic plaque development in hyercholesterolemic rabbits. Eicosapentanoic acid (EPA) converts arachidonic acid in cell membranes to Prostaglandin I‐3, which inhibits platelet aggregation and reduces blood clot formation. Atherogenesis and increased blood vascular fibrin clot formation can be induced in rabbits by feeding a diet containing 2% cholesterol for a month. Blood clot formation at the intimal surface in the aorta reduces oxygen availability which leads to lipid infiltration and plaque development. The effect of feeding atherogenic rabbits cod liver oil (CLO) containing 10% EPA, was studied here to determine its effect on blood levels of 2,3 Diphosphoglyceric Acid (2,3‐DPG).For a month, 12 white, New Zealand strain, male rabbits were fed atherogenic diet (AD) of 92% Purina Rabbit Chow(PRC), 6% Corn Oil and 2% Cholesterol. In the next 8 weeks, 6 rabbits were fed a control diet (CD) of PRC and 6 continued to be fed AD. Half of the CD and AD groups receied 0.8ml CLO daily. Blood 2,3‐DPG means after 2 weeks were: 1.51ug/ml in (CD ) vs 1.75 in the (CD + CLO) and 1.39 in ( AD) vs 1.81 in ( AD+ CLO) animals. After 8 weeks the means were 2.12 (CD) vs 2.35 (CD+CLO), and 1.51 (AD) vs 1.82 (AD+ CLO). The ( CD+CLO ) animals had the highest 2,3 DPG levels of all groups and the least aortal lipid infiltration. (AD+CLO) 2,3 DPG levels were significantly higher than in (AD) controls and they had lower lipid infiltration in their aortae. Blood plasma cholesterol levels in the AD groups were significantly lower in the ( AD+CLO ) vs the (AD) control rabbits.
Optimizing the Microfil Dye Perfusion Technique will Allow for Rat Cerebral Vascular Network Analysis through uCT Image Quantification
Authors: McCarter Monika , Balaez Alexander , Yarrow Joshua , Zubcevic Jasenka , Raizada Mohan 
Published: June 2021

IntroductionVascular pathophysiology is a hallmark of hypertension (HTN)‐linked cardiovascular disease, as increased peripheral resistance leads to vascular remodeling. Consistent with this is the evidence of links between impaired cerebral blood flow and hypoperfusion of the brainstem in HTN (1‐2). Thus, establishment of a technique for the cast dye perfusion would allow for 3D quantification of the microvasculature in order to investigate cerebral vascular changes associated with HTN and stroke.MethodsMale SHR and Wistar Kyoto (WKY) rats (3 and 12 week) were intracardially perfused using varying procedures. Focusing on limiting vessel damage and bubbling, Protocol 1 was as follows: 20 ml Microfil dye (47% dye, 51% diluent, 1% curing agent), 0.1 ml/min. Protocols 2,3,4 and 5 followed an identical procedure, however, perfusion speeds varied from 0.1 to 35 ml/min. A PBS/Nitroprusside/Heparin mixture was added to Protocol 6 to induce greater vessel dilation, prior to perfusion with a 1:4 dye to diluent ratio, with 0.2 ml of curing agent and 0.5 ml heparin at 50 ml/min. All procedures allowed for curing overnight at 4C.ResultsuCT imaging revealed that Protocol 6 provided the best perfusion with minimum damage to microvessels.ConclusionThus, our study has established a protocol to generate 3D images of the brain vasculature and puts us in a unique position to compare the impact of HTN on microvessels in the autonomic brain regions.AcknowledgementsThis research was made possible through funding from the APS UGSRF program. Special thanks to Mohan Raizada and lab for all of their support and guidance.
Clinical Salt‐Sensitive Hypertension Induced by Chronic Aortic Denervation in Rat is Dependent on the Activation of Intrarenal RAS
Authors: Rodriguez‐Martínez Manuel , López‐Rodríguez Juan , Calvo‐Turrubiartes Miriam , Casillas‐Santana Miguel , Martínez‐Mendoza Itzel 
Published: June 2021

We have reported in rats (BJMBR 46:868‐880:2013) that the interaction of chronic aortic denervation (AD) and high sodium diet (HNa, 8%) increases the likelihood of developing clinical salt‐sensitive hypertension (cSSHT). To assess whether intrarenal RAS activation is involved in cSSHT, mean arterial pressure (MAP, mmHg) and plasma total nitrogen oxides ([NOx]p, µM) were measured in two occasions in each rat: after 7 days on low sodium diet (LNa = 0.04%) and again after 21 days on high sodium diet (HNa, 8%) in three groups of conscious male Wistar rats: (SHM: n = 9) sham bilaterally chronic aortic denervated , (AD: n = 9) real bilaterally chronic aortic denervated and (AD + LOS: n = 9) AD plus Losartan (10 mg/kg/day) only during the 21 days on HNa. At the end, the renal medullary superoxide anion production (RMSAP, cpm/mg) and the urinary excretion of angiotensinogen (Uagt/Ucreat, µg/g) were measured too. SSi = Salt Sensitivity index = HNaMAP ‐ LNaMAP, mmHg; Δ[NOx]s = LNa[NOx]s ‐ HNa[NOx]s, µM. Values are mean ± SEM; ° p< 0.005, *p<0.0001 vs. LNaMAP; ♦p=0.03,# p=0.01 vs. SHM.

LNa
HNa
SSi
Δ[NOx]s
RMSAP

MAP
MAP

LNa‐HNa
HNa

SHM
116
122
6
16
1.8 x 106

n = 9
±2
±2
±1
±3.0
±0.2 x 106

AD
126#
140*#
14♦
14
4.8 x 106♦

n = 9
±2
±2
±2
±2.6
±0.6 x 106

AD+LOS
126#
132°#
6
17
4.5 x 106♦

n = 9
±2
±2
±1
±3.5
±0.5 x 106

Uagt/Ucreat samples are being processed and analyzed ConclusionsThe clinical Salt‐Sensitive Hypertension (cSSHT = SSi 蠅 10 and MAP 蠅 130, mmHg) induced by chronic aortic denervation in rat is dependent on the activation of intrarenal RAS. Supported by C13‐FAI‐03‐36.36
Sympathetic Overactivity to the Liver: A Possible Contributor to Hepatosteatosis in Diet‐Induced Obesity?
Authors: Young Colin , Morgan Donald , Rahmouni Kamal , Mark Allyn , Davisson Robin 
Published: June 2021

Obesity is associated with hepatic pathologies, such as steatosis and fibrosis, but the involvement of the autonomic nervous system in these processes remains unclear. Given that elevations in sympathetic outflow play a role in other obesity‐induced diseases (e.g., hypertension), we tested the hypothesis that obesity is associated with hepatic sympathetic overactivity. Male C57Bl/6 mice were fed a high fat diet (HFD; 60% fat; n=5) or normal chow (5% fat, n=6) for 20 weeks and were then instrumented for direct anesthetized recordings of multifiber sympathetic nerve activity (SNA) to the liver. Hepatic SNA recordings revealed a near doubling of basal sympathetic outflow to the liver in HFD mice and this was evident when evaluated as a frequency (33±2 vs 63±5 spikes/s, normal chow vs HFD, p<0.05) or integrated voltage (0.28±0.02 vs 0.46±0.03 volts/s/min, normal chow vs HFD, p<0.05). Removal of afferent input, via cutting of the hepatic nerve distal to the recording electrode, indicated that elevated efferent sympathetic outflow was a large contributor to the increased basal liver SNA (efferent SNA: 0.23±0.02 vs 0.36±0.03 volts/s/min, normal chow vs HFD, p<0.05). These findings provide the first direct evidence of hepatic sympathetic overactivity in obesity and suggest that elevated liver SNA may play a role in obesity‐mediated hepatic disorders, including hepatosteatosis.HL63887, HL84207, K99HL166776
Reduced Regional Cerebral White Matter Perfusion in Middle‐Aged Hispanic Adults
Authors: Pasha Evan , Tarumi Takashi , Gonzales Mitzi , Pearman Miriam , Haley Andreana , Tanaka Hirofumi 
Published: June 2021

BackgroundHispanics are at least 1.5 times more likely to have mild cognitive impairment and exhibit dementia symptoms 7 years earlier than non‐Hispanic Caucasians. Regional cerebral hypoperfusion has been implicated as an initial event in the pathogenesis of dementia.AimTo compare cerebral perfusion in brain regions susceptible to vascular related hypoperfusion in Hispanic and non‐Hispanic Caucasian adults.MethodsApparently healthy middle‐aged Hispanic (n=16) and non‐Hispanic Caucasian (n=16) subjects were matched across age, gender, years of education, and cognitive status. Arterial spin labeled perfusion magnetic resonance imaging estimated cerebral blood flow in a priori brain regions of interest.ResultsMean cerebral perfusion was significantly lower in the Hispanic cohort than matched non‐Hispanic Caucasian peers in the right (38±32 vs. 76±22 ml/100 g/min, p=0.005) and left posterior white matter (39±32 vs. 72±31 ml/100 g/min, p=0.047). These differences remained significant even after controlling for blood pressure (p<0.05).ConclusionsMiddle‐aged Hispanic adults demonstrated significantly lower cerebral perfusion to the right and left posterior white matter compared with matched non‐Hispanic Caucasian peers. Hypoperfusion in these regions may contribute to cerebrovascular changes that could lead to early cognitive declines in the Hispanic population.Supported in part by grants from the American Heart Association (09BGIA2060722, APH), the National Institute of Neurological Disorders and Stroke (R01NS75565, APH), the National Institute on Aging (F31 AG040890, MMG), and American Federation for Aging Research (8A0024, APH).
Sympathetic and respiratory activities during increases in osmolarity in an in situ rat preparation.
Authors: Silva Elaine , Bassi Mirian , Menani Jose , Zoccal Daniel , Pedrino Gustavo , Colombari Debora , Colombari Eduardo 
Published: June 2021

In the present study, we investigated the changes in the thoracic sympathetic (tSNA) and phrenic nerve activity (PNA) induced by hypertonic saline (HS) infusion in different concentrations in decorticated arterially‐perfused in situ rat preparations. Juvenile male Holtzman rats (P 28‐38, 60‐100 g, n = 6/group) were used. In one group of rats, intra‐arterial infusions of HS (0.175; 0.3; 0.7; 1.5 e 2 M NaCl; 200 µL each in 15 seconds) were made in ascending order and in another group only a single infusion of 2 M NaCl was done. Infusion of 2 M NaCl increased tSNA when combined with previous HS infusions in ascending concentrations (35.1 ± 5.6% vs. Ringer solution: ‐1.1 ± 2.1%, p<0.05), whereas single infusion of 2 M NaCl did not change tSNA (‐0.1 ± 2.1% vs. Ringer solution: 1.4 ± 1.9%). Infusion of 2 M NaCl did not induce significant change in the PNA either alone (3.0 ± 0.5 bpm, Ringer solution: ‐2.5 ± 1.5 bpm) or combined with previous HS infusions in ascending concentrations (4.9 ± 1.7 bpm vs. Ringer solution: 1.5 ± 0.4 bpm). The osmolality of the perfusate increased after HS infusion in ascending concentrations (306.5 ± 1.8 vs. pre infusion: 298.3 ± 1.6 mOsm/kg; p<0.05). These data show that acute 2 M NaCl infusion increases tSNA only when preceded by the administration of ascending concentrations of HS in the in situ rat preparations.Supported by Capes; CNPq; FAPEG and FAPESP
A Novel Method to Quantify Diaphragm Muscle Fiber Type Clustering in the Context of Sarcopenia
Authors: Vasdev Amrit , Greising Sarah , Medina Juan , Sieck Gary , Mantilla Carlos 
Published: June 2021

Sarcopenia is the age‐related decline of skeletal muscle function. Sarcopenia involves loss of motor neurons and the subsequent denervation of muscle fibers. Denervated muscle fibers can be re‐innervated through terminal axonal sprouting of neighboring axons. Given the predominant role of motor neurons in establishing muscle fiber type, we hypothesized that sarcopenia (and the associated partial denervatin effects) result in clustering of muscle fibers of the same type (classified by myosin heavy chain isoform composition). Fiber type specific immunofluorescence histology was used to quantify fiber clustering in murine diaphragm muscle (n=15) at 6 and 24 months of age. Clustering was analyzed using the distance between fibers of the same fiber type as well as quantification of the number of type‐identified fibers in a cluster. There was a 14% decrease to the closest fiber for type I and a 24% increase for type IIx and/or IIb fibers (P<0.001) in old vs. young mice. Additionally, a 34% increase to the 3 closest type IIx and/or IIb fibers was found (P<0.001). Changes in the interfiber distances for type‐identified fibers reveals important effects that consider changes in fiber size and proportion across disease conditions. This novel method of analyzing fiber type clustering may be useful in examining pathophysiological conditions of motor unit loss in neuromuscular disorders, myopathies, dystrophies, injuries, or amyotrophic lateral sclerosis.Supported by R01‐AG044615, T32‐HL105355, and the Mayo Clinic.
Role for Bromodomain‐Containing Protein 4 in Pulmonary Arterial Hypertension
Authors: Vaillancourt Mylène , Meloche Jolyane , Ruffenach Grégoire , Provencher Steeve , Bonnet Sébastien 
Published: June 2021

BackgroundPulmonary arterial hypertension (PAH) is associated with sustained DNA damage accounting for a PARP‐1‐dependent downregulation of miR‐204, promoting the expression of oncogenes (Survivin, Pim‐1). Once activated through the transcription factor NFAT, they contribute to the pro‐proliferative and anti‐apoptotic phenotype of PAH‐pulmonary arterial smooth muscle cells (PAH‐PASMC). In cancer, the epigenetic reader Bromodomain‐containing protein 4 (BRD4) sustains cell proliferation. Interestingly, BRD4 is upregulated by DNA damage and is a predicted target of miR‐204. We hypothesized that the PARP‐1/miR‐204‐dependent upregulation of BRD4 triggers the pro‐proliferative and anti‐apoptotic phenotype seen in PAH‐PASMC.Method/ResultsBRD4 is upregulated (immunoblot; p<0.01) in distal PAs and PASMC of PAH patients (n=9) compared to control (n=5). This increase is miR‐204 dependent, as miR‐204 upregulation using mimic in PAH‐PASMC decreases BRD4 (p<0.05). BRD4 activation in PAH‐PASMC induces Survivin and Pim‐1 expression (immunoblot; p<0.05), leading to mitochondrial hyperpolarization (TMRM; p<0.05), decreasing mitochondrial respiration (Seahorse XFe 24) and increasing NFAT activation (p<0.05), all of which were reversed upon molecular (siRNA) and pharmacological ((+)JQ1) inhibition of BRD4. BRD4 inhibition reverses PAH‐PASMC proliferation (Ki67; p<0.05) and resistance to apoptosis (TUNEL; p<0.05). In vivo, BRD4 inhibition reverses sugen/hypoxia induced PAH in rats.ConclusionThrough a miR‐204‐dependent mechanism, BRD4 upregulation triggers the expression of oncogenes contributing to the proliferative and anti‐apoptotic phenotype seen in PAH‐PASMC, whereas BRD4 inhibition improves PAH.