bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of myogenic cell transplantation on collateral capillary arteriogenesis
Authors: Sivesind Padon M. , Hamzeinejad Vahid , Cardinal Trevor R. 
Published: June 2021

Current treatments for peripheral arterial occlusive disease (PAOD), including angioplasty and bypass grafting fail in up to 25% of patients, or are not indicated in up to 50%, so there is a need to develop additional treatment options. Patients with native collaterals have a better prognosis, so a treatment such as cell transplantation that promotes collateral arteriogenesis is a potential PAOD treatment. Unfortunately, bone marrow derived stem cells, the main cell type that has been investigated, have limited clinical effectiveness in enhancing pre‐existing collateral growth. Therefore, delivering a stem cell type native to the collateral‐containing tissue, such as myogenic stem cells, could have improved outcomes. Additionally, about 20% of patients never develop collaterals, and no one, to our knowledge, has evaluated the effect of cell therapy on collateral capillary arteriogenesis (CCA), which can reperfuse ischemic tissue in animals without native arteriolar collaterals and therefore represents a potential therapeutic target in patients who lack native collaterals. To test the hypothesis that myogenic cells enhance CCA, we ligated the spinotrapezius feed artery in Balb/C mice to induce CCA, and delivered myogenic cells, thrombin (positive control), or vehicle to the muscle. Seven days post ligation, ‐‐‐‐arterialized collateral capillary (ACC) number and diameter were determined. As expected, thrombin increased ACC number, but myogenic cells had no effect, 9.3 ± 0.5 vs 7.1 ± 0.4, respectively. However, myogenic cells increased ACC diameter as compared to untreated (12.1 ± 0.8 μm vs 10.3 ± 0.3 μm, respectively) and both myogenic cells and thrombin increased the maximum ACC diameter (29.9 ± 3.4 μm and 27.9 ± 2.0 μm vs 18.8 ± 1.1 μm, respectively). These results are consistent with previous studies indicating that thrombin enhances arteriogenesis and suggest that myogenic cells have a similar effect, but likely without the deleterious pro‐inflammatory effects of thrombin. Because myogenic cells increase arteriogenesis and macrophages are an essential part of arteriogenesis, we also tested the hypothesis that myogenic cells increase macrophage content by performing CD68 staining. Although macrophage number increased following ligation, neither myoblasts nor thrombin further increased macrophage number. The lack of difference in macrophage number despite enhanced CCA could be because the day‐7 timepoint was too late, as macrophages peak around day‐3, or because a shift towards either classically‐activated macrophages or alternatively‐activated macrophages, which have a greater effect on arteriogenesis, would not be detected by the CD68 stain. Therefore, future studies may include a day‐3 timepoint and a stain for alternatively‐activated macrophages.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebrovascular Hyper‐permeability and Memory Impairment after Cortical Contusion Injury during Hyperhomocysteinemia in Mice
Authors: Muradashvili Nino , Tyagi Suresh C. , Lominadze David 
Published: June 2021

Traumatic brain injury (TBI) is the devastating public health problem worldwide. It is accompanied with inflammation, cerebrovascular dysfunction, and memory impairment. The latter is known to be greatly affected by cellular prion protein (PrPC). Elevated blood level of Homocysteine (Hcy), called hyperhomocysteinemia (HHcy) is considered to be an independent inflammatory and high risk factor for many cerebrovascular diseases. HHcy was found in TBI patients. High level of Hcy is associated with increased levels of another inflammatory marker fibrinogen (Fg). In the present study, we tested the hypothesis that HHcy exacerbates TBI‐induced macromolecular protein extravasation resulting in enhanced Fg‐PrPC complex formation leading to reduction in short‐term memory.Cerebrovascular permeability was studied in cystathionine‐β‐synthase heterozygote knockout (CBS+/−) mice, a well‐known model of HHcy. As a control we used wild type (WT, C57BL/6J) mice. Mice were subjected to cortical contusion injury (CCI) or sham operation (sham). Cerebrovascular permeability was assessed by measuring the fluorescence intensity of Alexaflour 647‐labeled bovine serum albumin (647‐BSA) in extravascular space using an intravital fluorescence microscopy. Formation of Fg‐PrPC complex in brain sample cryosections was studied using immunohistochemistry and confocal microscopy. Short‐term memory changes were evaluated by a novel object recognition test (NORT) and Y maze spontaneous alternation and two trial recognition tests.Pial venular permeability to 647‐BSA was greater in all experimental animals with CCI compared to that in respective sham‐operated mice. However, in injured CBS+/− mice the protein leakage was greater (201±6 % of baseline) than that (166±9 % of baseline) in WT animals with CCI. Enhanced Fg‐PrPC complex formation was found in WT animals after CCI compared to that in sham mice. Increased depositions of Fg and PrPC and their complex formations were detected in CBS+/− mice compared to those in control WT group. Short‐term memory deficiency after CCI was noted in both mice groups. However, reduction in short‐term memory (difference in discrimination ratios between sham and CCI groups) defined by NORT was greater (0.4±0.05) in CBS+/− mice compared to that (0.2±0.04) in control WT mice.Thus, our study reveals a novel, additive effect of HHcy in TBI‐induced memory impairment, which can be therapeutically targeted in future.Support or Funding InformationSupported in part by NIH grant NS084823, AHA grant 17SDG33670372, and UofL SOM Basic grant 57139This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebrovascular Reactivity and Cognitive Function in Hypertensive and Non‐Hypertensive Adults
Authors: Lefferts Wesley , DeBlois Jacob P. , Mammolito Girolamo L. , Dressel Elizabeth A. , Receno Candace N. , Heffernan Kevin S. 
Published: June 2021

Hypertension and its vascular consequences contribute to cognitive dysfunction. Accelerated cerebrovascular aging in hypertension may impair cognitive function by impairing cerebrovascular reactivity. Cerebrovascular reactivity in hypertension is often assessed by manipulating CO2, which may not directly reflect reactivity occurring from changes in metabolic supply and neuronal demand during a cognitive task (i.e. neurovascular coupling). The purpose of this study was to compare macro‐ and microvascular hemodynamics at rest and during cognitive activity (Stroop task) in 30 middle‐aged, medicated hypertensive (HTN) and 30 age‐, sex‐, and body mass index (BMI)‐matched non‐HTN adults (56±6 yrs, BMI 28.2±2.9 kg/m2; 32 men). Brachial mean pressure (MP) was measured from an oscillometric cuff. Macrovascular measures included common carotid artery (CCA) mean blood flow from ultrasound and middle cerebral artery (MCA) mean blood velocity from transcranial Doppler. Conductance was calculated as blood flow and mean velocity relative to MP for CCA and MCA, respectively. Microvascular measures included prefrontal cortex (PFC) oxy‐(O2Hb) and deoxyhemoglobin (HHb), and tissue saturation index (TSI) via near‐infrared spectroscopy. Data were analyzed using a 2×2 repeated measures ANOVA but are expressed as change from baseline. Accuracy and hit reaction times were computed to assess cognitive performance. Stroop accuracy (Non‐HTN 95±4%, HTN 95±3%) and reaction time (Non‐HTN 960±142 ms, HTN 998±148 ms) were similar between groups (p>0.05). CCA and MCA conductance were not altered during Stroop (p>0.05). PFC HHb decreased similarly in both groups (p<0.05), while TSI response during Stroop tended to differ (p=0.09) between groups. A significant interaction revealed HTN increased O2Hb during Stroop, while O2Hb was unaltered in Non‐HTN. Differences in O2Hb responses remained when expressed relative to MP. Changes in PFC TSI were positively associated with Stroop accuracy in HTN (r=0.41, p<0.05) but not Non‐HTN (r=0.16, p>0.05). Our data indicate that HTN and Non‐HTN have similar pressure‐mediated macrovascular hyperemia to cognitive activity resulting in a maintenance of macrovascular conductance. HTN exhibit greater increases in O2Hb to achieve similar cognitive performance compared to Non‐HTN, perhaps suggestive of early cerebral aging in HTN. The augmented O2Hb response may contribute to overall tissue oxygenation (TSI) which is associated with preserved cognitive performance in HTN.Support or Funding InformationSupported by an AHA Pre‐Doctoral Fellowship and Foundation Research Grant from ACSMThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Impact of Grey Matter Normalization on Cerebrovascular Reactivity
Authors: Katchen Karly B. , Miller Kathleen B. , Howery Anna J. , Corkery Adam T. , Johnson Sterling C. , Rowley Howard A. , Barnes Jill N. 
Published: June 2021

Grey matter atrophy occurs with age; however, most studies on cerebral blood flow responses to hypercapnia and age do not normalize to grey matter volume. It is possible that adults with lower brain blood flow and lower brain blood flow responses simply have less grey matter. This is especially relevant in the context of aging, where grey matter declines 0.83% per year. Therefore, the purpose of this study was to determine the impact of grey matter volume (GM) normalization on the cerebrovascular reactivity quantification in young and older healthy adults. We recruited 15 young (YA: age = 26 ± 4 y; BMI = 23 ± 1 kg/m2) and 10 older (OA: age= 64 ± 3 y; BMI= 22 ± 3 kg/m2) habitually exercising men and women. Middle cerebral artery velocity (MCAv), mean arterial pressure (MAP), and end‐tidal carbon dioxide (ETCO2) were measured continuously at rest and during a stepped hypercapnia protocol. GM was calculated from a T‐1 weighted scan on a 3T MRI scanner and segmented using SPM12. Cerebrovascular conductance index (CVCi) was calculated as CVCi = MCAv/MAP. Reactivity was calculated as the linear relationship between the change in ETCO2 and the change in MCAv and CVCi. GM normalization was performed by dividing MCAv and CVCi by GM. GM was significantly higher in the young compared with the older adults (YA: 0.71±0.02 L; OA: 0.62±0.01 L; p<0.001). MCAv reactivity values normalized to GM were significantly higher than those of raw MCAv reactivity in both young (YA: Raw: 1.7±0.3 cm/s/mmHg; Norm: 2.3±0.4 cm/s/L/mmHg; p<0.001) and older adults (OA: Raw: 2.0±0.3 cm/s/mmHg; Norm: 3.3±0.4 cm/s/L/mmHg; p<0.001). However, MCAv reactivity was not different between groups for both the raw and GM normalized data (p>0.05). Similar results were found for CVCi reactivity such that CVCi reactivity values normalized to GM were higher than raw CVCi reactivity for both young (YA: Raw: 0.017±0.002 cm/s/mmHg2; Norm: 0.023±0.003 cm/s/L/mmHg2; p<0.001) and older adults (OA: Raw: 0.015±0.002 cm/s/mmHg2; Norm: 0.024±0.003 cm/s/L/mmHg2; p<0.001). However, there were no significant differences in CVCi reactivity between young and older adults for both raw and normalized data (p>0.05). These results suggest that GM normalization changes reactivity values similarly between young and older habitually exercising adults.Support or Funding InformationSupported by National Institute of Health grant HL118154.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sympathetic Nervous System Reactivity in Women following Preeclamptic Pregnancies
Authors: Usselman Charlotte W. , Adler Tessa E. , Leone Cheryl , Paidas Michael J. , Stachenfeld Nina S. 
Published: June 2021

Women who have had preeclamptic pregnancies are at risk for life‐long cardiovascular disease. However, the factors contributing to this risk have yet to be established. Sympathetic nervous system dysregulation has been proposed to contribute to cardiovascular dysfunction during preeclamptic pregnancies. Therefore, we examined muscle sympathetic nerve activity (MSNA) at baseline and during a chemoreflex stimulus in women 6–24 months postpartum following a preeclamptic pregnancy (PE; n=6, age 28±2 y, BMI 27±3 kg/m2, 17±4 months postpartum). We hypothesized that MSNA responses to apnea would be greater in PE relative to control subjects, that is, women 6–24 months following a healthy pregnancy and with no history of disordered pregnancies (HP; n=6, 31±6 y, BMI 29±5 kg/m2, 17±4 months postpartum). Integrated MSNA recordings were obtained at baseline and during a voluntary end‐inspiratory apnea. Baseline mean arterial pressure (MAP; 87±10 vs 95±10 mmHg, P=0.2), total peripheral resistance (TPR; 13±3 vs 14±1 mmHg/L/min, P=0.4), and heart rate (HR; 74±5 vs 74±13, P=0.9) were similar in PE vs HP. Baseline MSNA was higher in PE compared to HP (26±9 vs 14±6 bursts/100 heartbeats, P<0.01). The voluntary apnea was maintained for a similar duration in PE and HP (44±17 and 45±10 sec, P=0.9), without any difference in mean MAP (93±14 and 99±11, P=0.4), TPR (14±4 and 14±2, P=0.6), or HR (74±8 and 81±22, P=0.5) between groups. To discern between mild and moderate phases of chemoreflex stress, the apnea was divided into initial (i.e. first half) and latter (i.e. second half) phases for subsequent analyses. The initial phase of the apnea elicited a large increase in MSNA in the PE women which exceeded that observed in HP (37±13 vs 19±11, P=0.03, respectively). The peak sympathetic response observed in the latter half of the apnea was similar between PE and HP (56±21 vs 49±13 bursts/100hb, P=0.5). Thus, the sympathetic nervous system response to a mild chemoreflex stimulus is exaggerated in women who have had preeclampsia within the past 6–24 months relative to women without a history of preeclampsia. We have demonstrated that a recent history of preeclampsia is associated with chronic sympathetic activation as well as greater sympathetic reactivity. We propose these changes to the sympathetic nervous system contribute to the life‐long risk for cardiovascular disease in formerly preeclamptic women.Support or Funding InformationFunded by the Paul Titus Fellowship, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High fat diet increases salt sensitivity and promotes hypertension and kidney inflammation/injury in Dahl salt sensitive rats
Authors: Fernandes Roxanne , Garver Hannah , Harkema Jack J. , Galligan James J. , Fink Gregory D. , Xu Hui 
Published: June 2021

Salt sensitivity of blood pressure and renal inflammation/injury are common in obesity associated hypertension. We and others have previously reported that high fat (HF) diet promotes hypertension in Dahl salt sensitive (SS) male rats ingesting a “normal” salt diet (NS, 0.3% NaCl). It is unclear if the HFNS diet would induce renal inflammation/injury and if a low salt intake would reduce blood pressure and renal inflammation/injury in this model of obesity‐associated hypertension. Therefore in the current study, Dahl SS male rats were fed a normal fat (NF, 10% kcal from fat) and HF (60% kcal from fat) diet with different salt contents for 24–26 weeks after weaning (3 weeks of age). HFNS (n=9) rats had a much higher MAP than NFNS rats (n=10) at the end of the study (158±1 mmHg versus 130±1 mmHg, P<0.05). However, in low salt fed rats (LS, 0.1% NaCl), MAP at the end of the study was only slightly higher in HFLS (n=4) than NFLS (n=5) rats (131±1 mmHg vs 121±3 mmHg, P<0.05). Renal tissues were taken from rats at 24 weeks after feeding. Renal injury was histologically characterized as the grade of tubular proteinosis, tubular atrophy, glomerulofibrosis, and interstitial fibrosis. Renal inflammation was identified by counting the infiltration of macrophages (CD68) and T cells (CD3) in cortex and medulla. HFNS feeding caused much more severe renal injury and higher CD68 infiltration than NFNS, but this was not observed in HFLS fed rats. NSNF rats also showed more CD68 infiltration than all LS rats. HFNS and NFNS rats showed similarly higher CD3 infiltrations than all LS rats. HFNS fed rats exhibited significantly increased expression of renal proliferating cell nuclear antigen (PCNA, a cellular proliferation marker) but this was not seen in HFLS fed rats. Body weight was not significantly greater, but visceral adipose accumulation was higher, in HFNS and HFLS rats compared to NFNS and NFLS fed rats, respectively. HF fed rats did not show significant alterations in plasma levels of fasting glucose, insulin, leptin, aldosterone or serum creatinine compared to NF rats. Our studies suggested that high fat diet associated hypertension and renal inflammation/injury in Dahl SS male rats are both salt‐sensitive, but are not associated with obvious metabolic disorders. Low salt diet may be useful in protecting against obesity associated hypertension and renal inflammation/injury.Support or Funding InformationNIH NHLBI 2P01HL070687This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Overexpression of ELABELA in the Renal Medulla Attenuated DOCA/salt‐Induced Hypertension in Sprague Dawley rats
Authors: Deng Mokan , Fu Ziwei , Chen Yanting , Hu Jiajia , Wang Weidong , Yang Tianxin , Wang Lei , Zhu Qing 
Published: June 2021

ELABELA (ELA) is a recently identified 32‐residue hormone peptide predominantly expressed in the adult kidney, especially in the renal collecting ducts, indicating it may play an important role in the renal regulation of fluid/electrolyte homeostasis and salt sensitivity of blood pressure. Our preliminary results showed that the mRNA levels of ELA were significantly inhibited by 60% in the renal medulla from DOCA/salt hypertensive SD rats. The current study was to test whether inhibition of the renal medullary ELA is responsible for the salt sensitive hypertension induced by DOCA/salt. Male SD rats were uninephrectomized and treated with DOCA pellet (sc, 100 mg/rat) plus 1% NaCl drinking water for 3 weeks. Renal medullary ELA levels were increased by >5 folds in SD rats via transfection of ELA overexpression plasmid into the renal medulla. Functionally, urinary sodium excretion in rats treated with ELA plasmid was dramatically increased compared with that in rats with vehicle plasmid after chronic sodium loading (30.14±7.99 vs. 60.39±10.41 mmole/kg.24h). Furthermore, DOCA/salt‐induced hypertension was significantly attenuated in rats treated with ELA plasmid. The mean arterial pressure in these animal groups was 101 ±6 mmHg on control rats treated with vehicle plasmid, 147 ±10 on DOCA rats treated with vehicle plasmid, 125 ± 12 on DOCA rats treated with ELA plasmid, respectively. These results suggest that inhibition of renal medullary ELA by DOCA/salt treatment may represent a novel pathogenic mechanism for salt‐sensitive hypertension and that induction of ELA expression in the renal medulla could be a therapeutic approach for the treatment of salt‐sensitive hypertension.Support or Funding InformationNational Natural Science Foundation of China ( No. 81600322, No. 81770707, No. 91439205)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Olfactory Receptor 1393 Contributes to the Progression of Diabetes
Authors: Shepard Blythe D. , Koepsell Hermann , Pluznick Jennifer L. 
Published: June 2021

Olfactory receptors (ORs) are G protein‐coupled receptors which serve to detect odorants in the nose. It is now appreciated that these receptors have roles beyond odorant detection and serve important functions in a number of different tissues. Included in the list of ectopic ORs is olfactory receptor 1393 (Olfr1393). We recently found (Shepard, et al Sci Rep 2016) that Olfr1393 is a novel regulator of sodium glucose co‐transporter 1 (Sglt1) surface expression in the renal proximal tubule. Olfr1393 is localized to the apical membrane of the proximal tubule and knockout (KO) mice present with mild glycosuria and improved glucose tolerance despite euglycemia and normal insulin levels. The Sglts have emerged as therapeutic targets for patients with type II diabetes, and these inhibitors have been shown to attenuate the progression of diabetic nephropathy including restoring glomerular filtration rate (GFR) through increased distal sodium delivery. Given Olfr1393's role as a regulator of Sglt1 in the proximal tubule, we hypothesized that the absence of Olfr1393 may attenuate the progression of diabetes and hyperfiltration. To examine this, Olfr1393 WT (n= 7) and KO (n=12) mice were challenged with a high fat diet (60% kcal) for 16 weeks to induce early stage diabetes. As expected, Olfr1393 WT mice displayed significant weight gain and impaired glucose tolerance. GFR (as measured via the transcutaneous detection of FITC‐Sinistrin clearance) was measured after 0, 11.5, and 16 weeks on the diet and, as expected, WT mice developed glomerular hyperfiltration by 16 weeks (μl/min GFR: week 0 – 187.3±16.4; week 16 – 401.0±17.0). Conversely, high fat diet‐fed KO mice exhibited a significant improvement in glucose tolerance (Area under the curve in thousands: WT – 43.0±6.4; KO – 27.9±2.6, p=0.02) and a blunted hyperfiltration (μl/min GFR: week 0 – 170.7±13.6; week 16 – 312.7±25.1; week 16 WT vs KO p=0.02). Collectively, this data indicates that renal Olfr1393 can contribute to the progression of type II diabetes, likely as a regulator of Sglt1.Support or Funding InformationNIDDKThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.