bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaping During Pregnancy Results in Arterial Stiffness in Offspring
Authors: Aboaziza Eiman , O'Reilly Juliana , Moore Josh , McLaughlin Sarah , Olfert I. Mark , Chantler Paul 
Published: June 2021

Electronic cigarettes (Ecigs) are promoted as effective smoking cessation tools, and consequently widely used among pregnant women who are motivated to quit tobacco cigarette smoking. Emerging evidence demonstrates that Ecigs can be dangerous to cardiovascular health. Babies born to women who vape represent a uniquely vulnerable population for this type of exposure, because they may be adversely impacted during a critical developmental period. It is unknown if cardiovascular harm potential of Ecigs without nicotine is conferred to offspring of vaping mothers. Pulse wave velocity (PWV) provides an indirect measure of arterial stiffness (with stiffer vessels having higher PWV) and can be useful for characterizing cardiovascular disease progression.Sprague‐Dawley rat dams were exposed to either nicotine‐free Ecig vapor (Ecig0, Joyetech eGrip OLED using 5‐sec puffs @17.5 W) or ambient air. Exposure consisted of 20 puffs over 1‐hour each day, 5 days/week, and resulted in an average daily TPM of ~120 mg/m3. Maternal exposure started on gestational day 2 and continued until pups were weaned (postnatal day 21). Pups were never directly exposed. Left common carotid arteries (LCCA) of 4‐month old pups (n=5 per group) were noninvasively imaged via Doppler ultrasound. PWV was measured using the regional transit‐time (TT) method (PWV=Δd/Δt; where d is distance between proximal (downstream to aortic arch) and distal (upstream of bifurcation) points on the LCCA, and t is the arrival time of pulse wave upstroke relative to R‐wave peak on ECG). Repeated (≥3) measurements were made for each variable and averaged. TT measurements were performed using a Vevo2100 ultra high frequency ultrasound platform with heart rate monitoring system (VisualSonics Inc, Toronto, ON, Canada). Results were processed using VisualSonics analysis software.Left common carotid arterial PWV (mean ± SD) in the Ecig0 group (6.6 ± 2 m/s) was significantly higher (p<0.01) than in the air control group (3.2 ± 0.7 m/s).Offspring exposed to nicotine‐free Ecig vapor in utero had higher PWV than controls, indicating stiffer arteries and an increased risk for cardiovascular disease. Further studies will determine the long‐term implications of this vascular impairment. Clinicians and policy‐makers need to be aware of these risks to discourage pregnant women from using Ecigs (with or without nicotine).Support or Funding InformationWVU Cancer Institute Philip R Dino Innovative Research Grant (IMO); APS STRIDE Fellowship (JO); AMIF: NIH S10RR026378, P20RR016440, P30GM103488, P20RR016440, P30GM103488 and U54GM104942 (SM)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Signaling of IL13 through IL4Ra Promotes Cardiac Regeneration
Authors: Paddock Samantha J , Wodsedalek Dylan J , Kenarsary Aria , O'Meara Caitlin C 
Published: June 2021

IntroductionDuring the first week of life, neonatal mice are able to regenerate their hearts after injury with minimal scarring. Our lab has previously published that the global knockout of anti‐inflammatory cytokine Interleukin 13 (IL13) inhibits neonatal cardiac regeneration in mice. IL13 primarily acts through the IL4Ra/IL13Ra1 heterodimer receptor to promote cell cycle activity. However, how IL13 specifically signals in the heart to promote this phenotype remains unexplored. We hypothesize that the deletion of the IL4Ra component of IL13's receptor complex will lead to a similar lack of regeneration in the mouse heart.MethodsTo delineate IL13 signaling mechanisms in the mouse, we utilized various knockouts of IL13 signaling—IL13 global knockout mice, IL4Ra global knockout mice, and C57/BL6 wildtype mice. With cardiomyocytes (CMs) isolated from these models, we analyzed the dynamics of downstream factors of recombinant IL13 (rIL13) in vitro. Additionally, at postnatal day 1 (P1), our mouse models were given apical resections to remove up to 10% of the apex of the heart. After resection, we investigated mRNA and protein expression of downstream markers, as well as CM proliferation at different time points. We also analyzed overall regenerative potential through echocardiography and Gömöri trichrome staining.ResultsIn vitro administration of rIL13 to wildtype neonatal mouse CMs resulted in strong, but transient activation of AKT and ERK1/2, which have been shown to be pro‐survival and pro‐proliferative respectively. In our IL4Ra KO mice, we see an attenuation of this signaling. At 7 days post resection (dpr), we see a significant decrease in proliferating CMs from IL13 KO mice when compared to wildtype. Additionally, at 21dpr in vivo, we observe significant fibrotic apical scars in IL13 KO mice, indicating lack of cardiac regeneration.ConclusionFrom these results, our data suggests that depletion of IL13 and its receptor, IL4Ra, inhibits regenerative pathways in the heart.Support or Funding InformationAmerican Heart AssociationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Role of Thbs‐1/CD47‐Drp1 signaling following ischemia reperfusion in the aging heart
Authors: Kelm Natia , Beare Jason , Yuan Fangping , LeBlanc Amanda 
Published: June 2021

Ischemia reperfusion (IR) injury leads to activation of dynamin‐related protein (Drp‐1), causing mitochondrial fission and generation of reactive oxygen species (ROS), but the molecular mechanisms that activate Drp‐1 are not known. The purpose of this study was to establish the signaling pathway between Thbs‐1/CD47 and fission protein (Drp‐1) through PGC‐1 following IR in advancing age.MethodsFemale Fischer‐344 rats were divided into 4 groups: Young Control, Young+IR, Old Control and Old+IR. Echocardiography measurements were done at baseline and 72 hours after IR (30 minutes of ischemia,72 hrs of reperfusion). After evaluation of heart function and coronary flow using vevo3100, hearts were explanted and mitochondrial ROS generation was measured using MitoPY1 (O2·−), as well as protein levels of Thbs‐1, PGC‐1, and Drp‐1. In vitro, rat aortic endothelial cells (RAEC) received hypoxic conditions to mimic IR in vivo model. Cells were treated with SiRNA for PGC‐1 or control scrambled SIRNA and then underwent hypoxia challenge to evaluate PGC‐1 effect on Drp‐1. Cell lysate was collected for Western Blot after 36 hours of transfection.ResultsMitochondrial O2·− generation in heart tissue increased in both age groups following IR. Old animals experiencing diastolic dysfunction at the baseline, after IR they exhibited reduced systolic function and exacerbated diastolic dysfunction compared to young controls. IR induces Thbs‐1 and Drp‐1 expression in young and old hearts. SiRNA to PGC‐1 enhanced levels of Drp‐1 in RAECs and increases ROS generation after hypoxia.ConclusionLeft ventricular diastolic dysfunction during IR is potentiated due to increased generation of ROS. These results highlight a novel signaling pathway by which Thbs‐1 regulates mitochondrial fission (Drp‐1) and ROS generation during hypoxia, and presumably, following IR. Inhibiting Thbs‐1 immediately after IR may prevent Drp‐1‐mediated mitochondrial fission and is likely to improve diastolic function of the heart by reducing ROS‐mediated cardiomyocyte damage in the aged population.Support or Funding InformationNIH R01 AG05358 Gheen's FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vascular Contributions to Intracranial Hemodynamic Pulsatility and Pulsatile Dampening in Adults
Authors: Lefferts Wesley K , DeBlois Jacob P , Augustine Jacqueline A , Heffernan Kevin S 
Published: June 2021

The brain is a high‐flow organ that requires continuous, non‐pulsatile blood flow. Intracranial blood flow pulsatility depends on the ability of the large elastic arteries and cerebrovasculature to dampen pulsatile hemodynamics transmitted from the heart. Aging is accompanied by large artery stiffening and reductions in cerebrovascular dampening, ultimately increasing intracranial pulsatility. It is unclear what hemodynamic forces may be responsible for these age‐related changes in the transmission and dampening of intracranial pulsatility across the lifespan. The purpose of this study was to explore hemodynamic contributors to intracranial pulsatility and pulsatile dampening in 244 adults between 35–85 yr (49% female, 56±12 yr, 27±4.2 kg/m2). Intracranial pulsatile dampening was calculated as the ratio between common carotid and middle cerebral artery (MCA) blood velocity pulsatility index (PI) measured via Doppler. Carotid ultrasound and wave intensity analysis were used to measure carotid diameter, forward compression wave energy (W1), wave reflection index (RIx), and forward traveling expansion wave (W2). Aortic (carotid‐femoral) and carotid pulse wave velocity (PWV) were assessed via tonometry and carotid ultrasound, respectively, and expressed as a ratio (aortic:carotid PWV). Carotid pulse pressure (PP) was measured via tonometry. Multiple regression was used to examine the contributions of 1) age, sex, BMI, aortic:carotid PWV, carotid diameter, PP, and W1 to intracranial pulsatility (MCA PI); and 2) age, sex, BMI, aortic:carotid PWV, carotid diameter, RIx, and W2 to intracranial pulsatile dampening. After entering all variables, significant predictors of MCA PI included age (β,0.44), aortic:carotid PWV (β,0.16), PP (β,0.29), and W1 (β,0.20; R2=0.50, p<0.01). Significant predictors of intracranial pulsatile dampening included age (β,−0.47), sex (β,−0.43), and RIx (β,0.26; R2=0.53, p<0.01). Our data confirms recent literature linking age, exaggerated stiffening of the aorta compared to carotid artery, and extracranial hemodynamics to intracranial pulsatility in the MCA. Moreover, our findings indicate age, sex, and wave reflections in the carotid artery impact the ability of the cerebrovasculature to dampen transmission of pulsatile hemodynamics. These data highlight the potential utility of the large extracranial arteries as therapeutic targets to reduce intracranial pulsatility and importance of carotid wave reflections in dampening intracranial pulsatility.Support or Funding InformationFunded in part by an ACSM Foundation Research Grant (WKL), AHA Predoctoral Fellowship (WKL), and Dairy Research Institute/Dairy management Inc. Grant 1154 (KSH).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Reduction in Cardiac Function Precedes Structural Adaptations in Experimental Spinal Cord Injury
Authors: Fossey Mary , Poormasjedi‐Meibod Malihe‐Sadat , Hayes Brian , Erskine Erin Laurel , Azad Reathm K , Granville David James , Ramer Matt Steven , West Christopher Roy 
Published: June 2021

IntroductionChronic high‐thoracic spinal cord injury (SCI) is associated with systolic dysfunction, cardiomyocyte atrophy and the upregulation of major proteolytic pathways in the heart. How such dysfunction manifests with time is presently unknown.MethodsMale Wistar rats underwent complete SCI at the 3rd thoracic spinal level (T3‐SCI; n=10) or dorsal durotomy (SHAM; n=5). T3‐SCI rats were terminated at different time points: three days post‐SCI (3‐day SCI; n=5) or seven days post‐SCI (7‐day SCI; n=5). SHAM rats were terminated at seven days post‐durotomy. On termination day, prior to euthanasia, left‐ventricular (LV) catheterization was performed to assess cardiac function. Additionally, cardiac tissue was collected for histological analysis to quantify cardiomyocyte dimensions (standardized to femur length).ResultsRelative to SHAM, T3‐SCI rats at both 3‐day and 7‐day post‐SCI exhibited reduced stroke work (SW; p=0.036), load‐independent contractile function (inferred with end‐systolic pressure‐volume relationship, ESPVR; p=0.0013) and maximal rate of LV systolic pressure increment (dP/dtmax; p=0.0070). The maximal rate of LV relaxation (i.e. ‐dP/dtmin; p=0.019) was reduced at 3‐day and 7‐day post‐SCI vs. SHAM; however, tau (time constant of isovolumic relaxation) was not different (p=0.15). There were no differences for any functional indices between 3‐day vs. 7‐day SCI. Histological analysis of cardiomyocytes indicates no significant differences in length and width in SCI groups vs. SHAM (length p=0.20; width p=0.24).ConclusionSystolic cardiac function decreased significantly in both 3‐day and 7‐day SCI rats vs. SHAM. This indicates a rapid onset of cardiac dysfunction following T3‐SCI. Cardiomyocyte atrophy was not present in either 3‐day or 7‐day SCI rats, implying a reduction in cardiac function precedes structural remodeling.Support or Funding InformationHeart and Stroke Foundation of Canada (HSFC), International Collaboration on Repair Discoveries (ICORD) and Blusson Integrated Cure Partnership (BICP).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dislocation of Lysyl Oxidase and Deformation of Cardiomyocytes in Response to Myocardial Ischemic Injury in Mice
Authors: Chu Qing , Xiao Ying , Song Xin , Kang Y. James 
Published: June 2021

Lysyl oxidase (LOX), a copper‐dependent amine oxidase, is located in the intercalated discs between cardiomyocytes in the heart and responsible for the catalysis of collagen and elastin cross‐linking of the extracellular matrixes. However, in response to myocardial ischemic injury, LOX is dislocated to the cytosol, along with deformation, of cardiomyocytes in the ischemic myocardium. The present study was undertaken to explore the relationship between LOX dislocation and the deformation of cardiomyocytes in response to myocardial ischemia. Male C57BL/6J mice aged 8–12 weeks old were subjected to left anterior descending (LAD) coronary artery ligation to induce ischemic injury. The hearts were collected at 1st, 4th, or 7th day after the surgery and cut into frozen/paraffin sections to detect LOX location and the morphological changes of cardiomyocytes. Most of the survived cardiomyocytes in the ischemic infarct area were deformed from the rod‐shaped to the rounded detected on the 7th day after the surgery. Corresponding to the deformation of cardiomyocytes, the junction between cardiomyocytes become disturbed, and the intercalated discs disappeared. Connexin 43 (Cx43), an important gap junction protein located in the intercalated discs, was significantly reduced in the ischemic infarct area at day 1, but slightly recovered at day 7 after LAD ligation. However, the recovered Cx43 proteins were mainly located in the cytosol of cardiomyocytes. LOX proteins were increased gradually from day 1 to day 7 in the ischemic infarct area in comparison with the sham‐operated controls, and were mostly dislocated in the cytosol of cardiomyocytes. The results suggest that in response to ischemic injury, dislocation of LOX in cytosol of cardiomyocytes is likely responsible at least in part for the breakage of the junction between cardiomyocytes, leading to loss of the cell polarity and impaired contractile function of cardiomyocytes.Support or Funding InformationScientific research funds of West China Hospital, Sichuan UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PP242, mTOR inhibitor, decreases phenylephrine‐induced vascular contractility in hypertensive and normotensive arteries
Authors: Quinones Patricia Martinez , Patel Viral , Lewis Steven , McKenzie Jaine , Warner Alex , McCarthy Cameron , Wenceslau Camilla , Komic Amel , Webb R Clinton 
Published: June 2021

Cardiovascular disease is the leading cause of death in cancer survivors. The short‐term and long‐term cardiotoxic effects of targeted chemotherapeutics is not well known. PP242, a dual inhibitor to mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and 2 (mTORC2), is a targeted therapy in clinical trials for various malignancies including bladder, ovarian and gastric cancer. mTORC1 inhibition has been associated with heart failure, while mTORC2 inhibition has been considered cardioprotective. We hypothesized that PP242 leads to enhancedcontractile response to phenylephrine (PE), and impaired Acetylcholine (ACh)‐induced relaxation. We studied the effects of PP242 on the contractility and relaxation of aortic rings and mesenteric resistance arteries (MRA) of male Wistar rats (12–15 weeks old, n=4) and spontaneously hypertensive rats (SHR) (15–18 weeks old, n=6) on a wire myograph. Vessel segments were exposed to PP242 (500nM) for one‐hour incubation. Normotensive aortic rings exposed to PP242 showed a decreased contractile response to PE (LogEC50±SEM, Ctrl:−7.617±0.178 vs Drug: −7.292±0.129) and increased relaxation to ACh (LogEC50±SEM, Ctrl:−6.917±0.164 vs Drug: −7.588±0.164). SHR aortic rings exposed to PP242 (LogEC50±SEM, Ctrl:−7.606±0.129 vs Drug: −7.124±0.118) showed decreased contractility but no difference in ACh‐induced relaxation. No differences were observed in normotensive MRA. SHR MRA showed decreased PE‐induced contraction (LogEC50±SEM, Ctrl:−5.402±0.060 vs Drug:‐−5.322±0.065) and increased ACh‐induced relaxation (LogEC50±SEM, Ctrl:−7.992±0.117 vs Drug:−8.139±0.092). Our data suggest that dual inhibition of mTORC1 and mTORC2 with PP242 may provide a cardioprotective effect by limiting vasoconstriction and may be a good therapeutic agent for hypertensive cancer patients. However, long term treatments with this targeted therapy need to be evaluated for vascular dysfunction induction, as the hypocontractile effect could contribute to failure of the cardiovascular system, which could be associated with cardiotoxicity.Support or Funding InformationNIH P01 HL134604 (RCW), k99GM11888 (CFW)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Therapeutic Telomerase Reactivation for the Prevention of Doxorubicin‐Induced Cardiotoxicity
Authors: Chatterjee Shambhabi , Hofer Teresa , Gupta Shashi Kumar , Thum Thomas , Bär Christian 
Published: June 2021

BackgroundDoxorubicin (DOX) is one of the most potent chemotherapy agents. Its clinical use however, is restricted due to the severe risk of cardiotoxicity, presumably attributed to high levels of reactive oxygen species (ROS) leading to cardiomyocyte death. Telomerase prevents cell death through maintaining telomeres. In addition, telomerase has non‐canonical, anti‐apoptotic and pro‐survival traits, likely owing to detoxification of ROS. However, telomerase is silenced in adult murine and human hearts.PurposeTo test whether pharmacological reactivation of telomerase may be effective as a therapeutic strategy to prevent doxorubicin‐induced cardiotoxicity.Methods and ResultsWe used a AAV9‐based gene therapy approach to reinstate telomerase expression in cardiomyocytes in a mouse model of chronic DOX‐induced cardiotoxicity. Telomerase treated mice presented with preserved heart weights in comparison to AAV‐empty controls after DOX treatment. Histopathological analyses revealed that this rescue was accompanied by preserved cardiomyocyte size and reduced apoptosis rates. This was also reflected by improved cardiac function parameters determined by echocardiography and Millar catheterization. At the molecular level we observed altered mitochondria morphology and reduced mitochondrial fission in response to telomerase expression. In line, Western blotting post telomerase reactivation revealed lower levels of the mitochondrial fission protein Drp1, which plays a known role in cardioprotection. Complementary in vitro experiments confirmed anti‐apoptotic effects of telomerase in DOX treated human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes.ConclusionOur data suggest that cardiac‐specific telomerase reactivation could be a novel strategy for the prevention of doxorubicin‐induced cardiotoxicity in cancer survivors.Support or Funding InformationThis work was supported by the DFG (BA5631/2‐1 to CB) and ERA‐CVD Network (EXPERT grant to TT).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardioprotective and Hypocholesterolemic Effect of Ethanolic Extract of Mormodicalcharantial in Isoproterenol‐Induced Myocardial Infarction in Adult Wistar Rats
Authors: UBHENIN ABRAHAM EHINOMHEN , INNIH SILVANUS OLUSONYA 
Published: June 2021

ISO was used to induce MI by intraperitoneal injection at the dose of 100mg/kg to Wistar rats Serum lipid profile and cardiac marker enzymes were obtained and then measured calorimetrically. The results show that isoproterenol‐induced myocardiac infarction were associated with significant (p<0.05) increase in the activities of cardiac marker enzymes in the serum with concomitant decrease in the activities of these enzymes in the myocardial tissue as compared to control group. There were also significant (p<0.05) increase in serum level of total cholesterol , trigyceride, low density lipoprotein and very low density lipoprotein in the group injected with isoproterenol ( group ii) as compared with control group . Pretreatment with leaf extract of Mormodicalcharantial significantly (p<0.05) prevented this alteration of the lipid profile and also of the activities of these cardiac marker enzymes both in the serum and myocardial tissue as compared to isopreterenol‐induced control group. Mormodicalcharantialpossesses cardioprotective effects.Support or Funding InformationThe authors receive no grant for this research but however are grateful to the Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Benin, for the use of their research laboratory also acknowledge the technical help of Prof. P.O. Udia , Dept. of Biochemisry, University of Benin, Benin City, Nigeria,This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.