bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Light Pollution Affect the Development of Atherosclerosis?
Authors: Wendroth Robert H. , McGann Eric G. , Howatt Deborah A. , Pendergast Julie S. 
Published: June 2021

Exposure to light at night has been steadily increasing since industrialization. Light at night comes from light bulbs, light pollution produced by cities, and more recently from the widespread use of personal electronics (smart phones, tablets, laptops) at night. Previous studies in outbred mice have shown that dim light at night (DLAN) disrupts circadian rhythms and increases body weight, but it is unknown whether DLAN affects the development of cardiovascular disease. In this project, we are testing the hypothesis that DLAN accelerates the development of atherosclerotic lesions in C57BL/6J Apolipoprotein E‐deficient (ApoE−/−) mice. We single‐housed male ApoE−/− mice in light‐tight boxes at 7 weeks of age for 1 week in 12h light:12h dark (12L:12D) and then in DLAN (12h light: 12h dim 5 lux light) for 12 weeks. Control mice were maintained in 12L:12D for 13 weeks. Body weights did not differ between ApoE−/− mice in 12L:12D and DLAN. In 12L:12D, ApoE−/− mice had a robust daily rhythm of eating behavior that peaked during the night. However, after a few days in DLAN, ApoE−/− mice had a low‐amplitude eating behavior rhythm that persisted for the entire experiment. Preliminary data also suggest that ApoE−/− mice in DLAN had increased atherosclerotic lesion area and serum cholesterol levels compared to ApoE−/− mice in 12L:12D. These data suggest that DLAN disrupts the daily rhythm of eating behavior and may also increase atherosclerosis.Support or Funding InformationThis research was supported by the National Institutes of Health awards P20GM103527 and R03DK107851, an American Physiological Society Undergraduate Summer Research Fellowship, and the University of Kentucky. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelial Cell Pannexin1 Modulates Severity of Ischemic Stroke by Regulating Cerebral Inflammation and Myogenic Tone
Authors: Good Miranda Elizabeth , Eucker Stephanie A. , LI Jun , Bacon Hannah M. , Lang Susan M. , Butcher Joshua T. , Johnson Tyler J. , Zuo Zhiyi , Isakson Brant E. 
Published: June 2021

Ischemic stroke is a leading cause of morbidity and mortality in the United States; however, there currently exists only one effective acute pharmacological therapeutic intervention. Purinergic signaling has been shown to regulate vascular function and pathological processes, including inflammation and arterial myogenic reactivity, and plays a role in ischemic stroke outcome. Purinergic signaling requires extracellular purines; however, the mechanism of purine release from cells is unclear. Pannexin1 (Panx1) channels are novel purine release channels expressed throughout the vascular tree that couples regulated purine release with purinergic signaling. Therefore, we examined the role of smooth muscle and endothelial cell Panx1 in cerebral ischemia/reperfusion injury outcomes using conditional cell‐type specific transgenic mice. Deletion of endothelial cell Panx1, but not smooth muscle cell Panx1, significantly reduced cerebral infarct volume 24 hrs post‐reperfusion following a 90‐min ischemic injury. Infiltration of leukocytes into brain tissue and development of cerebral myogenic tone were both significantly reduced when mice lacked endothelial Panx1. Interestingly, Panx1 regulation of myogenic tone was unique to the cerebral circulation, as mesenteric myogenic reactivity and blood pressure were independent of endothelial Panx1. Overall, deletion of endothelial Panx1 mitigated cerebral ischemic injury by reducing inflammation and myogenic tone development, indicating that endothelial Panx1 is a possible novel target for therapeutic intervention of ischemic stroke.Support or Funding InformationNIH F32 HL131399, NIH P01 HL120840, NCI P30 CA044579‐23This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
SUBSTANCE P REGULATES INFLAMMATORY PATHWAYS IN LYMPHATIC MUSCLE
Authors: Kumar Amy , Lee Yang , Muthuchamy Mariappan , Chakraborty Sanjukta 
Published: June 2021

Substance P (SP), a neuropeptide that acts through the neurokinin receptors is associated with the sensory innervation of lymphoid tissue and modulates lymphatic contractile function and lymph flow. SP signaling is associated with several inflammatory pathologies. The role of lymphatics in body fluid homeostasis, lipid absorption and inflammation and immunity rely on the contractility of the lymphatic muscle cells (LMCs). We have shown that lymphatic contractile dysfunction is associated with perturbations in inflammatory mechanisms and that SP activates both inflammatory and contractile pathways in lymphatics. However, the specific inflammatory pathways and the resultant cytokines activated by SP in LMCs is unknown. We hypothesized that SP stimulates the pro‐survival AKT and MAPK pathways, and increases pro‐inflammatory cytokines. Cultured rat mesenteric LMCs were treated with SP (1 mM) and total RNA and protein were isolated at different time points (6 hr and 24 hr). Western analysis was carried out to detect the total and phosphorylated forms of AKT, JNK, GSK3b, b‐catenin, FOXO1 and PDCD4. b‐actin was used as control. The relative levels of inflammatory cytokines and chemokines, and specific inflammatory microRNAs (miRNAs) were analyzed by real time PCR. Our results indicate that SP activates the AKT and JNK pathways to significantly increase inflammatory cytokine and chemokine expression, and induces expression of miR 17–5p, miR19b and miR186 in the LMCs. Additionally, SP stimulates expression of genes, involved in lymphatic remodeling. Taken together our data demonstrate that SP activates multiple inflammatory signaling pathways in the LMCs that contribute to an inflammatory response in lymphatics during pathological conditions.Support or Funding InformationAmerican Heart AssociationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
An Ex Vivo Platform for Studying Angiogenesis in Perfused Microvascular Networks
Authors: Motherwell Jessica , Katakam Prasad , Murfee Walter 
Published: June 2021

A challenge in tissue engineering biomimetic models for studying angiogenesis is building the physiological complexity of real microvascular networks. Utilizing an alternative top‐down approach, our laboratory recently introduced the rat mesentery culture model as an ex vivo experimental platform for investigating the multi‐cellular dynamics involved in angiogenesis within an intact microvascular network. However, a current limitation of the model is that microvessels are not perfused. The objective of this study was to demonstrate the feasibility of perfusing microvascular networks during the culture of rat mesentery tissue. Adult Wistar rat mesentery tissues were harvested along with a feeding second order arteriole and venule, and then transferred to a customized tissue chamber for perfusion. The arteriole was cannulated with a glass pipette (40 – 60 μm diameter) and secured in place with 7–0 suture. Injection with blue food dye through the cannulated arteriole identified the lumens of vessels across the hierarchy of intact microvascular networks and confirmed successful perfusion. Tissues with cannulated arterioles were cultured in the perfusion chamber up to three days with either minimum essential media (MEM) or MEM supplemented with 10% serum. Live/dead labeling confirmed that cannulated mesentery tissues remain viable after three days in culture. Additional labeling with BSI‐lectin identified endothelial cells along microvascular networks and confirmed the tissues were undergoing angiogenesis, characterized by increases in vascular density and capillary sprouting. These results demonstrate the ability to perfuse intact microvascular networks ex vivo in cultured mesentery tissues and supports the novelty of the rat mesentery culture model as a biomimetic tool for investigating angiogenesis.Support or Funding InformationNIH R01AG049821This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of aging on vasomotion responses to varying rates of local heating.
Authors: Del Pozzi Andrew T. , Martin Zachary T. , Soave Kayla M. , Hodges Gary J. 
Published: June 2021

We compared the cutaneous microvascular vasomotion responses of 8 young (23 ± 1 yr) and 8 older (68 ± 2 yr) adults in the forearm and leg using laser‐Doppler fluxmetry (LDF) and wavelet analysis to investigate endothelial, neurogenic, and myogenic activity. We measured cutaneous microvascular responses at uncontrolled basal temperature (27 ± 2.2 °C), controlled basal temperature (33 °C), and initial vasodilation (onset of heating), and sustained vasodilation, at 42 and 44 °C, in response to both a slow (0.1 °C · 10 s‐1) and a fast (0.5 °C · 10 s‐1) local heating protocol. At baseline (no heating), there were no differences between the groups (all P > 0.05). At a controlled local temperature of 33 °C (thermoneutral), neurogenic activity was higher in the leg of the young compared to the older group (P = 0.04). Following the initiation of the heating protocols, the young participants responded with higher neurogenic activity in the forearm compared to the older group during fast local heating (P = 0.03), but not in response to slow local heating (P > 0.05). In the leg, the young group had higher endothelial nitric oxideindependent activity compared to the older group (P = 0.01) for both heating protocols. The young group also had an increase in endothelial nitric oxide‐dependent activity during the slow protocol (P < 0.001), while the older cohort experienced increases in neurogenic (P = 0.02) and myogenic (P = 0.04) activity. Following 35 min at 42 °C, neurogenic activity was significantly increased in the leg of the older group compared to the young group during the slow heating protocol (P = 0.02). Furthermore, after increasing local temperature from 42 to 44 °C, the older adults had higher endothelial nitric oxide‐independent activity (P = 0.04) in the forearm of the fast protocol while the young subjects had higher neurogenic activity (P = 0.04). Neurogenic activity in the leg of the older group was increased (P = 0.02) during the fast protocol at 44 °C. These results suggest that regional differences in the response to local heating persist with age and that the primary mechanisms responsible for vasodilation caused by local heating are diminished with age; however, overall vasodilation is offset by the other mechanisms. Moreover, our results suggest that as we age the reliance on endothelial activity shifts from endothelial nitric oxide‐dependent to endothelial nitric oxide‐independent mechanisms. These data suggest that the cutaneous bioavailability of nitric oxide is diminished with age.Support or Funding InformationBall State University SPA Fellows StipendThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Critical role of angiotensin II type 2 receptors in the control of mitochondrial and cardiac function in angiotensin II‐preconditioned rat hearts
Authors: Nuñez Rebeca , Javadov Sabzali , Escobales Nelson 
Published: June 2021

Angiotensin II preconditioning (APC) involves an angiotensin II type 1 receptor (AT1‐R)‐dependent translocation of PKCɛ and survival kinases to the mitochondria leading to cardioprotection after ischemia‐reperfusion (IR). However, the role that mitochondrial AT1‐Rs and angiotensin II type 2 receptors (AT2‐Rs) play in APC is unknown. We investigated whether pretreatment of Langendorff‐perfused rat hearts with losartan (L, AT1‐R blocker), PD 123,319 (PD, AT2‐R blocker) or their combination (L+PD), affects mitochondrial AT1‐R, AT2‐R, PKCɛ, PKCδ, Akt, PKG‐1, MAPKs (ERK1/2, JNK, p38), mitochondrial respiration, and cardiac function. The results indicate that expression of mitochondrial AT1‐Rs and AT2‐Rs were enhanced by APC 1.91‐fold and 2.32‐fold, respectively. Expression of AT2‐R was abolished by PD but not by L, whereas the AT1‐R levels were abrogated by both blockers. The AT1‐R response profile to L and PD was also shared by PKCɛ, Akt, MAPKs, and PKG‐1, but not by PKCδ. A marked increase in state 3 (1.84‐fold) and respiratory control index (1.86‐fold) of mitochondria was observed with PD regardless of L treatment. PD also enhanced the post‐ischemic recovery of RPP by 74% (p<0.05) compared with APC alone. Losartan, however, inhibited the rate pressure product (RPP) by 44% (p<0.05) before IR and reduced the APC‐induced increase of post‐ischemic cardiac recovery by 73% (p<0.05). These findings suggest that APC upregulates angiotensin II receptors in mitochondria and that AT2‐Rs have a permissive effect on AT1‐R‐dependent signaling and suppress mitochondrial respiration and cardiac function. These results support a critical role of mitochondrial AT2‐Rs in the control of cardiac function in APC.Support or Funding InformationSupported by the National Institutes of Health (NIH) Research Centers in Minority Institutions (RCMI) Program grant No. G12M007600, National Heart, Lung, and Blood Institute (NHLBI) grant SC1HL118669 (SJ), and the University of Puerto Rico.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dopamine Receptor D3 Agonist (Pramipexole) Abolishes Morphine‐Induced Cardiac Fibrosis in Mice
Authors: Gaweda Gabriel G. , Iyer Rugmani P. , Shaver Patti R. , Grilo Gabriel A. , Dinkins Mai‐Lynne , Stoffel Hamilton J. , Clemens Stefan , de Castro Brás Lisandra E. 
Published: June 2021

Prolonged morphine exposure leads to desensitization of the G protein‐coupled mu‐opioid receptor (MOR). Additionally, extended morphine exposure has been shown to associate with cardiac dysfunction. This is problematic for patients undergoing withdrawal from extended morphine pain management, especially those with pre‐existing heart conditions. Recent literature suggests mechanistic interactions between MOR and the dopamine receptor D3 (DRD3). The purpose of this study was to investigate whether a DRD3 agonist (pramipexole, 0.5 mg/kg/day, i.p.; DRD3ag) could reduce morphine‐induced cardiac dysfunction in mice. Thirty mice were randomly divided into 5 groups (G1–G5, Figure 1) and treated with morphine (2 mg/kg/day, i.p.) for 7 days (D7). Two groups were euthanized after morphine tolerance was established at D7 (G1, morphine only; G2, morphine + DRD3ag). The other 3 groups (D14) underwent a subsequent 7‐day period of morphine withdrawal (G3, withdrawal no treatment; G4, morphine + DRD3ag until D7 followed by withdrawal until D14; G5, morphine until D7 followed by withdrawal + DRD3ag until D14). Echocardiography was performed on each animal at D0 to establish a baseline for cardiac function, on D7, and again on D14. Histology and immunoblotting were conducted on the left ventricle (LV) to measure tissue fibrosis, myocyte hypertrophy, and DA receptor expression. Our data show that morphine treatment for 7 days followed by withdrawal induced cardiomyocyte hypertrophy and significantly increased myocardial fibrosis (both at D7 and D14). Picrosirius red staining showed that DRD3ag treatment completely abolished morphine‐induced fibrosis, independent of treatment time. Moreover, significantly decreased cardiomyocyte hypertrophy was noted in all groups receiving DRD3ag in the morphine withdrawal phase. Immunoblotting shows that morphine withdrawal significantly reduced DRD3 expression independent of the presence of DRD3ag. Our results suggest that using a DRD3ag as an adjunctive therapy with morphine could decrease morphine‐induced cardiac fibrosis, and subsequently blunt morphine‐dependent cardiac dysfunction. Further, our data suggest that the DRD3 agonist pramipexole has cardioprotective potential when administered during morphine withdrawal.Support or Funding InformationThe Brody School of Medicine Research Distinction Track, the Department of Physiology, and the Research and Graduate School at East Carolina University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of ICa,L by DHEA in Aortic Smooth Muscle Cells: Voltage‐dependency, Modulation by GPCR Signaling and Inhibition of Glucose‐6‐phosphate Dehydrogenase
Authors: Ochi Rikuo , Chettimada Sukrutha , Gupte Sachin A. 
Published: June 2021

Dehydroepiandrosterone (DHEA) is a hormone abundantly released from adrenal cortex as DHEA‐sulfate (DHEA‐S). DHEA‐S is released also in brain. DHEA and epiandrosterone (EPI), a metabolite of DHEA, produces relaxation of high‐K+ induced contraction of aortic smooth muscle (ASM). EPI increases voltage‐dependent inactivation (voltage‐dependent inhibition, VDI) of ICa,L in ventricular myocytes. Whole‐cell ICa,L was recorded as IBa from ASM cells (ASMCs) of A7r5 cell line and enzymatically isolated bovine coronary ASMCs to study mechanism and modulation of DHEA‐induced inhibition of ICa,L. DHEA produced VDI; acceleration of time course of inactivation, increase of inhibition by depolarization of holding potential (HP) and leftward shift of steady state inactivation curve; f∞, 2s‐V, obtained by 2 s conditioning pulse and f∞, HP‐V as a function HP. In addition, DHEA produced voltage‐independent inhibition (VIDI) represented by inhibition of peak amplitude (ICa,L,peak) of ICa,L elicited by pulses from hyperpolarized HPs. Window ICa,L (IWD) supplies Ca2+ in the E‐C coupling of ASM. IWD obtained from I–V of ICa,L,peak and f∞, HP‐V fitted well with recorded IWD and they were strongly inhibited by DHEA. Efficacy of DHEA‐induced VDI was reduced by rightward shift of f∞, 2s‐V curve produced by depletion of cholesterol by MβCD. Blocking of GPCR signaling by intracellular dialysis of GDP‐β‐S also shifted f∞, 2s‐V to the right and it produced decrease of DHEA‐induced inhibition of ICa,L at depolarized HP (VDI). DHEA and EPI are inhibitors of glucose‐phosphate‐dehydrogenase (G6PD), a redox‐related pentose‐phosphate pathway enzyme. 6‐Aminonicotinamide (6‐AN), another inhibitor of G6PD produced VIDI without inducing VDI. DHEA‐S that does not inhibit G6PD induced small but significant VDI at an order higher concentration of DHEA without generating VIDI. GPCR signaling and membrane cholesterol are indirectly involved in the modulation of DHEA‐induced VDI by affecting basal voltage‐dependent inactivation. The occurrence of VIDI by 6‐AN indicates that G6PD inhibition underlies DHEA‐induced VIDI. DHEA‐induced inhibition of IWD by VDI and VIDI contributes for DHEA‐induced relaxation of ASM.Support or Funding InformationNational Heart, Lung, and Blood Institute Grant RO1 HL‐085352 to S. A. Gupte.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Yoda1‐induced phosphorylation of the Akt and ERK1/2 does not require Piezo1 activation
Authors: dela Paz Nathaniel G. , Frangos John A. 
Published: June 2021

Piezo1 is a mechanosensitive cation channel that is expressed by endothelial cells (ECs) and can be activated by fluid shear stress. It has been previously shown to be important for a number of shear‐induced EC responses, ranging from increased intracellular calcium to cell alignment. Most recently, Piezo1 has been implicated as a critical regulator of vascular tone and blood pressure. Yoda1, a selective small molecule agonist of Piezo1, has been shown to induce responses similar to those activated by fluid shear stress in ECs, such as calcium influx. Since shear stress‐induced intracellular calcium release is known to cause activation of Akt and ERK1/2, we sought to determine whether Yoda1 stimulation of EC can lead to similar responses and whether they are Piezo1‐mediated. In this study, we show that Yoda1 can robustly activate both the Akt and ERK1/2 signaling pathways in ECs. Additionally, we found that the ion channel antagonists, gadolinium and ruthenium red, but not the specific Piezo‐blocking peptide, GsMTx4, effectively blocks Yoda1‐induced Akt activation. Taken together, our results suggest that despite Yoda1 being a selective Piezo1 agonist, Yoda1‐induced activation of these two independent signaling pathways is not entirely dependent on Piezo1 activation.Support or Funding InformationThis work was supported by NIH MERIT Award R37 HL040696 to J.A.F.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of BKCa Channels in Mesenteric Artery Vascular Smooth Muscle Tone of Diabetic Rats
Authors: HERNÁNDEZ‐GARCIA ANA PATRICIA , HERNÁNDEZ‐MÉNDEZ AURELIO , CHI‐AHUMADA ERIKA GUADALUPE , ALGARA‐SUÁREZ PAOLA , ESPINOSA‐TANGUMA RICARDO 
Published: June 2021

High conductance calcium‐dependent potassium (BKCa) channels are broadly distributed in different tissues where their activity is regulated by depolarization and calcium. The BKCa channels are abundant in vascular smooth muscle and their role regulating contractile tone has been widely discussed. Several studies have reported that in diabetes mellitus (DM) potassium currents mediated by these channels are diminished, especially in those located in small resistant vessels. BKCa channels are present in conducting arteries as well but their role in muscle tone seems to be small if any.The objective of this work was to study the role of BKCa channels in muscle tone of diabetic rat mesenteric arteries.Male Wistar rats (190 ± 10 gr in weight) were used and DM was induced by injecting streptozotocin (65 mg/kg) into de caudal artery. At 4, 8 and 10 weeks after streptozotocin or vehicle injection, rats were sacrificed and the mesenteric artery excised. We conducted isometric tension experiments using 10 micromolar of the selective channel activator NS1619 or 100 nM Iberiotoxin, a specific blocker of the BKCa channels applied at the peak of the maximum contraction induced by 10 microM phenylephrine (PE). We also took confocal fluorescence images to identify the localization of the alpha subunit ‐BKCa channel in mesenteric artery rings.Tension experiments show that NS1619 had no significant effect on the contraction induced by PE neither in control or DM rats, no matter the time of DM evolution (for example, at 10 weeks the percentage of relaxation was of 11.93 ± 4.73 in DM and of 9.0 in control group). Similarly, Iberiotoxin by itself had a weak contractile effect on the vascular tone of control and DM groups (for example, DM of 10 weeks the percentage of contraction was of 2.65 ± 1.89 and of 6.07 ± 3.34 in control rats). Immunofluorescence shows that BKCa alpha subunit channel is present within the endothelium, the smooth muscle cells and the adventitia. However, it is noteworthy that the alpha subunit is more abundant in endothelial cells and to a lesser extent in muscle cells where it can be seen mainly at the cytoplasm.We concluded that in spite that the BKCa channels are expressed in mesenteric artery smooth muscle, they do not participate in maintaining the muscle tone because they are present mainly intracellulary. At present we are conducting experiments to know the localization of the BKCa beta subunit and see if DM affect it.Support or Funding InformationSupported by CONACYT Grant 223350 to RETThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.