bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Risk Factors of Chronic Mountain Sickness
Authors: Richalet Jean‐Paul , Gazal Steven , Espinoza Jose R , Austerlitz Frédéric , Macarlupu Jose Luis , Leon‐Velarde Fabiola , Marchant Dominique , Gouya Laurent 
Published: November 2023

Chronic mountain sickness (CMS) is a pathological condition resulting from the loss of adaptation to high altitude. The syndrome is characterized by an excessive number of red blood cells (Excessive Erythropoiesis) associated with a high concentration of hemoglobin, hypoxemia and sometimes pulmonary hypertension. In the Peruvian Andes, the estimated prevalence of this condition is higher than 10% in the adult population living above 2500 m. The pathophysiology is not yet clearly established. Alteration of the control of ventilation, especially during sleep could induce a severe hypoxemia that would trigger excessive secretion of erythropoietin (EPO), leading to increased red cell production. We collected clinical and physiological data and blood samples in a cohort of 143 CMS patients and 101 control subjects living at high altitude in Cerro de Pasco (4300m). Leukocytes DNA was extracted by salting out procedure, DNA was quantified and qualified with NanoDrop™ 2000. We performed a genome wide association study using an Illumina HumanOmni5 array (4,301,332 SNPs). CMS was associated with low arterial O2 saturation and high body mass index. We evidenced several genes that could be related to a susceptibility to develop CMS or pulmonary hypertension (ATM, NPAT, PPARGC1A, ATP9A, WWOX). These pathways revealed as submitted to recent positive selection. Moreover, the admixture level of European low lander ancestry in the genome of this population seemed to influence the occurrence of CMS and the polymorphism of selected genes. A replication study is planned to confirm our preliminary results.Support or Funding InformationLaboratory of Excellence GrEx
Chronic intermittent hypoxia decreases the levels of corticotropin‐releasing hormone receptor 2 in the nucleus of the solitary tract in rats
Authors: Wang Lei , Mifflin Steve 
Published: November 2023

Corticotropin‐releasing hormone (CRH) has been suggested to play a role in the nucleus of the solitary tract (NTS) to regulate sympathetic activity and cardiovascular function but the distribution of CRH receptors in the NTS is not fully understood. In this study, we used RNAscope in situ hybridization and CD IGS rats to examine the mRNA levels of CRH receptor type 1 (CRHR1) and CRH receptor type 2 (CRHR2) in regions of the NTS (13.68 mm – 14.76 mm caudal to bregma) implicated in the regulation of sympathetic and cardiovascular function. The results showed that both CRHR1 and CRHR2 were expressed in the NTS. In general, there was higher mRNA levels of CRHR2 compared to CRHR1 in the NTS with CRHR2 being 319% ± 69% greater than CRHR1. The higher levels of CRHR2 compared to CRHR1 was mainly observed in the middle portion of the NTS we examined (13.8 mm – 14.28 mm caudal to bregma). We investigated whether CRHR1 and CRHR2 levels were influenced by chronic intermittent hypoxia (CIH), a model of sleep apnea associated with sympathetic excitation and hypertension in rats. We found that CIH did not affect the mRNA levels of CRHR1 but significantly decreased the mRNA levels of CRHR2 in the NTS by 34% ± 14%. These results demonstrate that both CRHR1 and CRHR2 mRNAs are expressed in the NTS and suggest that dys‐regulation of CRHR2 may contribute to CIH‐induced hypertension.Support or Funding InformationNIH HL088052
Vessel Reactivity and Blood Flow in Rats Exposed to Neonatal Supplemental Oxygen
Authors: Vellookunnel Shilpa , Chandrasekar Shreya , Sturgeon Madison , Murphy Austin , Hoover Michael , Bates Melissa 
Published: November 2023

Premature babies make up 12.8% of live births per year. Because their lungs are poorly developed, supplemental oxygen is a necessary treatment. Recent studies in our laboratory in a rat model of prematurity show that aortic pulse wave velocities were higher in rats exposed to neonatal supplemental oxygen, indicating significant aortic stiffening. This study aims to determine if supplemental oxygen also affects the downstream vasculature reactivity. We hypothesized that exposure to supplemental oxygen during the neonatal period will decrease vessel reactivity and we will observe smaller changes in blood flow with hypoxic and hypercapnic (vasodilator) challenges. Twelve month old rats exposed to 80% and 21% oxygen for eight days during the neonatal period were ventilated with hypoxia (12% O2), hypercapnia (5% CO2), and room air in the lab. After 10 minutes of exposure, 10 μm neutron‐activated BioPAL microspheres were injected into the left ventricle and allowed to circulate. The brain, liver, kidneys, spleen and heart were removed, hydrolyzed, and vacuum filtered. Microspheres were used to quantify changes in visceral blood flow. 80% O2 exposed rats and 21% O2 rats showed no significant difference in change in blood flow to the kidney, but further brain and visceral vascular beds are still to be measured. If a significant difference is found in the other vasculature, this would suggest supplemental oxygen exposure would decrease vessel reactivity in premature infants.Support or Funding InformationThe University of Iowa Start‐Up Fund
Ventilatory acclimatization to hypoxia in deer mice native to high altitudes
Authors: Ivy Catherine M , Scott Graham R 
Published: November 2023

Hypoxia at high altitudes constrains O2 supply to support metabolism, thermoregulation in the cold, and the aerobic scope needed for exercise. Many highland taxa appear to have physiological specializations for overcoming these challenges, but relatively little is known about the importance of hypoxia acclimation responses in high‐altitude natives, such as ventilatory acclimatization to hypoxia (VAH) and erythropoiesis. Highland taxa often possess a high haemoglobin‐O2 binding affinity, which safeguards arterial O2 saturation (SaO2) and tissue O2 delivery in hypoxia, but could foreseeably affect hypoxia acclimation responses. We examined this issue by comparing captive populations of deer mice (Peromyscus maniculatus) from high and low altitudes. Mice from each population were acclimated to normoxia and moderate hypoxia (12 kPa O2, simulating the PO2 at the native altitude of highlanders at 4300m) for 6–8 weeks. Highland mice were also acclimated to more severe hypoxia (9 kPa, the PO2 at ~7000m), which induces the same SaO2 in highlanders that lowlanders experience at 12 kPa. In lowlanders, hypoxia acclimation augmented the hypoxic ventilatory response (HVR), increased SaO2 in hypoxia, blunted the hypoxic depression of body temperature, increased blood [haemoglobin], and induced right ventricle hypertrophy (a sign of maladaptive pulmonary hypertension). Hypoxia acclimation had little effect on the HVR in highlanders, such that the hypoxic control of breathing appeared to be fixed like that in hypoxia‐acclimated lowlanders. Right ventricle hypertrophy did not occur in either moderate or severe hypoxia in highlanders, suggesting that they have blunted hypoxic pulmonary vasoconstriction and hypertension. The increase in blood [haemoglobin] was lower in highlanders than in lowlanders at 12 kPa, but highlanders mounted a robust increase in severe hypoxia (9 kPa), suggesting that differences in SaO2 and not the erythropoietic process contribute to differences in blood [haemoglobin] between populations. Therefore, high‐altitude adaptation appears to have blunted several hypoxia acclimation responses in deer mice.Support or Funding InformationSupported by NSERC of Canada.
Perinatal Supplemental Oxygen Alters the Ventilatory and Pulmonary Vascular Responses to Hypoxia in Adult Rats
Authors: Hoover Michael , Greiner Tyler J , Rotella Diane , Vellookunnel Shilpa , Chandrasekar Shreya , Bates Melissa 
Published: November 2023

Ascent to altitude is associated with increased ventilation and pulmonary vasoconstriction. These physiological responses are related in healthy subjects such that a high ventilatory drive is associated with blunted pulmonary vasoconstriction. Adults born prematurely and given supplemental oxygen at birth have a blunted ventilatory response to hypoxia. We hypothesized that the hypoxic ventilatory and pulmonary vasoconstrictor responses would be unrelated following neonatal exposure to supplemental oxygen. To test our hypothesis, we used a well‐established rat model of 80% O2 (OXY) exposure for 14 days post‐natally, with 21% O2 exposure as a control (CON). Six‐to‐nine months later, we assessed the ventilatory response to graded hypoxia using barometric plethysmography. We also catheterized the right and left ventricles to evaluate the hemodynamic response to 10 minutes of 12% O2 (hypoxia). We found that, to our surprise, OXY rats did not demonstrate a depressed ventilatory response to hypoxia. However, these animals experienced increased right ventricular systolic pressure in response to 12% O2. This was driven primarily by an increase in cardiac output and not increased vascular resistance. There was no relationship between the hypoxic ventilatory drive and right ventricular pressure. In CON animals, the increase in right ventricular pressure with hypoxia was driven primarily by vasoconstriction and, as expected, there was a relationship between the ventilatory and pressure responses. These data suggest that neonatal supplemental oxygen alters the hemodynamic response to hypoxia, possibly through enhanced sympathetic drive. The relationship between ventilation and pulmonary pressure may not translate to individuals born prematurely.Support or Funding InformationThe University of Iowa Start‐Up Fund
Aortic Hemodynamics and Cognition in Women with a History of Hypertensive Pregnancy
Authors: Miller Kathleen B , Fields Julie A , Harvey Ronée E , Lahr Brian D , Joyner Michael J , Miller Virginia M , Barnes Jill N 
Published: November 2023

A history of hypertensive disorders of pregnancy, including preeclampsia, place women at an elevated risk of developing hypertension and cognitive impairments as they age. The purpose of this study was to determine if aortic hemodynamics were related to cognition in postmenopausal women with a history of hypertensive disorders of pregnancy. We evaluated 33 postmenopausal women with a history of preeclampsia (PE: age = 59 ± 5 y; BMI = 29 ± 5 kg/m2; years since last pregnancy = 35 ± 3 y) and 29 postmenopausal women with a history of normotensive pregnancy (NTP: age = 59 ± 5 y; BMI = 26 ± 5 kg/m2; years since last pregnancy = 35 ± 3 y). Participants underwent a cognitive testing battery including letter‐number sequencing, trail making test B, letter fluency, and category fluency tests to evaluate executive functioning and working memory. Mean arterial pressure (MAP) was measured with a brachial blood pressure cuff. Applanation tonometry (SphygmoCor) was used to derive the aortic pressure waveform and calculate aortic systolic blood pressure (ASBP), aortic diastolic blood pressure (ADBP), augmentation index (AI), and augmented pressure (AP). There were no differences in cognitive scores between groups (p > 0.05). Brachial blood pressure (MAP: 103 ± 2 vs. 103 ± 3 mmHg) and aortic hemodynamic measures (ASBP: 123 ± 3 vs. 121 ± 3 mmHg; ADBP: 78 ± 2 vs. 77 ± 2 mmHg; AI: 31 ± 2 vs. 28 ± 1 %; AP: 17 ± 1 vs. 15 ± 1 mmHg) were also similar between PE women and NTP women, respectively (p > 0.05 for all). There were no associations between measures of aortic hemodynamics and cognitive scores in women independent of their pregnancy history (p > 0.05). When evaluating these relationships within each group, ADBP was significantly associated with worse scores for letter‐number sequencing and letter fluency in PE women (r = −0.433 and r = −0.441, respectively, p < 0.05). Taken together, our results indicate aortic hemodynamic measures are not associated with cognition in middle‐aged postmenopausal women with different pregnancy histories; however, future studies should address the influence of elevated aortic hemodynamic variables and the longitudinal change in cognitive function in postmenopausal women with different pregnancy histories.Support or Funding InformationNIH AG44170, NIH 118154
Pilot Study: Effects of Short‐term Summer School Program on Plasma Cognitive Marker and Non‐lipid Cardiovascular Risk Factors in Female Adolescents
Authors: Choi Myung Dong , Park Kyung‐Shin 
Published: November 2023

Education and health are the most important in school‐aged children and adolescents. It is well known that physical activity is a crucial component of health promotion and academic achievement in youth. However, schools do not provide recommended amount of physical activity during regular school seasons. It was reported that especially children in low socio‐economic status (SES) communities have poorer physical health and lower academic performance than children higher in SES. Recent studies indicated that increased physical education in school improves academic achievement and physical health. Thus, this pilot study seeks to find further evidence for the role of extended summer school programs including physical activities in relation to biomarkers of cognition and cardiovascular health in the area of low SES communities.PURPOSETo determine the effects of short‐term summer school programs including 2‐hour exercise per day on a cognitive marker and non‐lipid cardiovascular risk factors in female adolescents.METHODSThirty high school female students were recruited and 15 students were assigned to the summer school attendant group (SA) and completed summer school programs, including 2‐hour exercise daily for 5 weeks and 15 students were in non‐summer school attendant group (NSA). Plasma brain‐derived neurotrophic factor (BNDF), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) were measured immediately before and after summer vacation. One‐way ANCOVA was used to determine differences in BNDF, ICAM, and VCAM changes between the groups.RESULTSPlasma BNDF was elevated in SA group after summer vacation, compared with the NSA (12.8±2.2 ng/ml vs.10.0±1.7 ng/ml, respectively, P<0.001). Plasma ICAM level was decreased in the SA group after summer vacation, compared with the NSA (85.5±21.7 ng/ml vs. 109.2±25.9 ng/ml, respectively, P<0.001). Plasma VCAM was also decreased in the SA group after summer vacation, compared with the NSA (94.9±12.8 ng/ml vs. 109.5±18.4 ng/ml, respectively P<0.001).CONCLUSIONFive‐week summer school program may have a positive influence on memory retention and also decrease systematic cardiovascular risk factors in female adolescents. Thus, these preliminary findings support that school‐aged adolescents, while attending at summer school programs, might have beneficial outcomes on brain's memory function and the cardiovascular health, especially in low socio‐economic status communities. However, this pilot study may not provide a direct relationship among BNDF, memory retention, and academic achievement. Thus, further study is needed to verify whether or not increased plasma BNDF improves academic performance and/or skills.
Amelioration of Sodium Fluoride‐induced hypertension, cardio‐renal oxidative stress and genotoxicity by Azadirachta indica through antioxidant and extracellular signal‐regulated kinase (ERK) 1/2 signalling
Authors: Adejumobi Olumuyiwa , Omobowale Temidayo , Oyagbemi Ademola , Ayenuro Olubukola , Ola‐Davies Olufunke , Adedapo Adeolu , Yakubu Momoh 
Published: November 2023

In this study we investigated the protective effect of Azadirachta indica on sodium fluoride‐induced hypertension, oxidative stress, cardio‐renal toxicity and genotoxicity.Sixty rats were used in this study. They were divided into six groups each containing 10 rats. Group A served as the controls and they received distilled water only for a period of 14 days. Group B rats were administered distilled water only for the first 7 days and thereafter, sodium fluoride was adminstered at 600ppm in drinking water for another 7 days. Rats in groups C and D were pre‐treated with the methanolic extract of AI for the first 7 days alone at the dosages of 100mg/kg and 200mg/kg respectively and thereafter administered NaF at 600ppm in drinking water for 7 days. In groups E and F rats, distilled water alone was given to the rats during the first 7 days while 100mg/kg and 200mk/kg respectively of AI was co‐administered with NaF for another 7 days. At the termination, blood pressure measurement, electrocardiogram, antioxidant status and ERK 1/2 signaling were evaluated.Administration of NaF caused a significant (p<0.05) increase in systolic, diastolic and mean arterial blood pressure values relative to the control. Markers of oxidative stress such as myeloperoxidase, xanthine oxidase, malondialdehyde and hydrogen peroxide were significantly (p<0.05) increased relative to the controls. In addition, significant (p<0.05) decreases in the cardiac and renal contents of nitric oxide, protein and non‐protein thiol and reduced glutathione were also observed. Antioxidant, the activities of antioxidant marker enzymes; glutathione peroxidase, catalase and superoxide dismutase in both cardiac and renal tissues were significantly (p<0.05) decreased when compared with the control group. Treatment with NaF had no significant effects heart rate, QT and QTc (Bazett) values. NaF treatment also caused resulted in a reduction in the expression of Extracellular Regulated Kinase (ERK) 1/2 in both cardiac and renal tissues of treated rats. Genotoxicity studies showed that NaF treatment group elicited a significant (p<0.05) increase in the number of micronucleated polychromatic erythrocytes (MNPCE) in bone marrow when compared with the control group but this was ameliorated by treatment with AI.From this study, it can be concluded that treatment with AI conferred a protective effect NaF‐induced hypertension, oxidative stress, cardiorenal toxicity and genotoxicity through antioxidant and ERK 1/2 signaling in rats.Support or Funding InformationNone
Simvastatin Inhibits Myocardial Apoptosis through Targeting miR‐15a‐5p undergoing Cardiac Surgery
Authors: Ou Zhi‐Jun , Zhou Li , Liu Xiang , Li Yan , Xu Zhe , Zhang Xi , Xu Ying‐Qi , Wang Zhi‐Ping , Ou Jing‐Song 
Published: November 2023

We previously demonstrated that simvastatin inhibited myocardial apoptosis in patients undergoing cardiac surgery. MicroRNAs play an important role in inhibiting myocardial apoptosis. Whether simvastatin inhibitis myocardial apoptosis by regulating microRNAs remain unknown. 70 patients undergoing cardiac surgery, 35 from simvastatin group and 35 from control group, were enrolled. Simvastatin (20mg) was administered preoperatively for 5–7 days. Myocardial tissues biopsies were taken before and after surgery. microRNAs array was performed. Some of up or down expression of microRNAs were validated by real‐time PCR. The expression of proteins related to apoptosis and the up or down expression of microRNAs were detected. Some mRNAs were also detected by real‐time PCR and luciferase assays was performed. microRNAs expression profiling revealed that 317 miRNAs were differently expressed in the normal heart tissue, control and simvastatin group. Simvastatin significantly down‐regulated 94 miRNAs and up‐regulated 41 miRNAs. Among of them, miR‐15a‐5p was significantly decreased by simvastatin, which was validated by qPCR analysis. MiR‐15a‐5p was predicted to target Bcl‐2 mRNA on the position of 2529–2536 nucleotides. Coincident with the change of miR‐15a‐5p, the mRNA expression of Bcl‐2 were increased in simvastatin group. The protein expression of Bcl‐2 was upregulated in simvastatin group before surgery. These findings demonstrated that simvastatin inhibited myocardial apoptosis undergoing cardiac surgery, at least in part, by targeting miR‐15a‐5p/Bcl‐2 pathway.Support or Funding InformationNational Natural Science Foundation of China (81170271, 81370370, 81500215, 81600382, 81670392 and Distinguished Young Scholar 81325001), the Changjiang Scholars Program from Ministry of Education of China, the Guangdong Pearl River Scholars Program, International Cooperation Project (2015DFA31070) from the Ministry of Science and Technology of China, Guangdong Natural Science Fund Committee, China (2015A030312009), Sun Yat‐Sen University Clinical Research 5010 Program; Program of National Key Clinical Specialties, The five and five projects from The First Affiliated Hospital, Sun Yat‐sen University.
Pharmacological cardiac sympathetic afferent denervation in pacing‐induced heart failure
Authors: Senador Danielle , Kaur Jasdeep , Sala‐Mercado Javier A , Krishnan Abhinav C , Alvarez Alberto , Hanna Hanna W , Lovelace Abe T , Rasaiah Megan M , Altamimi Yasir H , O'Leary Donal S 
Published: November 2023

Chronic sympathoexcitation is a hallmark of congestive heart failure. Enhanced input from the cardiac sympathetic afferent reflex (CSAR) appears to be a major contributor to augmented central sympathetic outflow in heart failure (HF) in rats (Myocardial ischemia model. Wang et al., Hypertension, 2014) and dogs (Rapid ventricular pacing model. Wang and Zucker, Am. J. Physiol., 1996). Transient receptor potential vanilloid 1 (TRPV1) expressing cardiac afferent fibers are responsible for CSAR activation, since systemic (Zahner et al., J. Physiol., 2003) and epicardial (Wang et al., Hypertension, 2014) administration of resiniferatoxin (RTX), an ultra‐potent analog of capsaicin that degenerates TRPV1‐expressing neurons, can almost completely abolish CSAR activation in rats. We tested whether epicardial application of RTX degenerates cardiac sympathetic TRPV1‐expressing neurons therefore reducing CSAR reactivity, in canines with pacing‐induced HF. In control studies, stimulation of left ventricular afferents containing TRPV1 via topical application of capsaicin (2 mg/ml) caused a pressor response and tachycardia (Δ=+15 mmHg, +44bpm). These responses were abolished by acute topical application of RTX (50 μg/mL). Experiments were repeated 9 weeks following RTX treatment and the subsequent induction of HF via rapid ventricular pacing. RTX pretreatment abolished the responses to capsaicin, whereas CSAR was preserved in HF if no RTX pretreatment was performed. TRPV1 expressing neuronal degeneration was evaluated through immunofluorescence histology (IFH) in left ventricle tissue samples, with triple labeling for DAPI (nuclei marker), PGP9.5 (nerve terminal marker,) and TRPV1 receptors. RTX treated tissue samples showed considerably lower TRPV1 positive staining when compared to non‐treated samples. The present study validates RTX as a potential therapeutic method to block excessive CSAR activation in pacing‐induced heart failure dogs, therefore expanding pharmacotherapy options for heart failureSupport or Funding InformationNIH HL55473 and HL126706