bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐regulation of Cardioprotective Gene Expression by NF‐kappaB, AP‐1, and STAT3 in Late Phase Ischemic Preconditioning
Authors: Tranter Michael , McGuinness Myc , Paulding Waltke , Haar Lauren , Ren Xiaoping , Jones W. Keith 
Published: June 2021

IntroductionWe have shown that NF‐κB regulates the expression of over 200 genes in late ischemic preconditioning (IPC) and its activation is necessary for the cardioprotection of late IPC. We have also demonstrated that Hsp70.3 is one of these NF‐κB regulated genes whose expression is necessary to elicit late IPC protection.ResultsUsing a novel non‐viral DNA delivery agent to apply transcription factor decoys to the in vivo murine heart, we show that, in addition to NF‐κB, transcriptional blockade of AP‐1, or STAT3 prior to IPC abrogates the late phase of cardioprotection. We hypothesize that NF‐κB, AP‐1, and STAT3 co‐regulate a common subset of genes, including Hsp70.3, that are critical for late phase IPC cardioprotection. Results using in vitro reporter assays demonstrate coordinated regulation of the Hsp70.3 promoter by NF‐κB, AP‐1, and STAT‐3. We also used PCR based gene microarrays to examine in vivo expression changes of 238 previously identified NF‐κB‐dependent genes under conditions of AP‐1 and STAT3 inhibition after IPC to identity additional genes co‐regulated by this trio of IPC requisite transcription factors.ConclusionsThe set of genes whose expression is co‐dependent on multiple cardioprotective transcription factors after IPC are likely to underlie common critical pathways of cardioprotection and may represent novel therapeutic targets for the treatment of ischemic heart disease.This work was supported by NIH grant R01 HL63034 (WKJ).
Myocardial TRPV activation associated with high fat diet and cardioprotection
Authors: Haar Lauren Lynn , Rubinstein Jack , Tranter Michael , Jiang Min , Jones W Keith 
Published: June 2021

Clinical data suggests obese patients have improved outcomes after myocardial infarction as compared to non‐obese patients. It has been shown that cardioprotective effects of high fat diet are dependent upon transient receptor potential vanilloid 1 (TRPV1) channel activation. However, there are six TRPV channels and, to date, little is known about the expression or function of TRPV 2–6 in the heart. The goal of this study was to investigate the expression of the six TRPV channels in the myocardium and to evaluate their potential role in the link between obesity/high fat diet and cardioprotection. Our results show expression of all six TRPV genes in the myocardium. In addition, mice subjected to ischemic stimuli or maintained on a high fat diet display increases in TRPV channel expression. We hypothesize that TRPV channel activation by high fat diet plays a role in modulating myocardial function and cell survival. To understand the role of TRPV channels in the myocardium, we utilized echocardiography and examined the effect of TRPV channel activation, using relatively selective pharmacological agents, on in vivo cardiac function. We also investigated the expression and effect of TRPV channel activation on the function of isolated cardiomyocytes. TRPV channels play an important role in regulating cardiac function and may represent potential therapeutic targets for the treatment of cardiac pathologies.This work was supported by NIH grant R01 HL63034 (WKJ).
Endothelin‐1 blockade with bosentan attenuates15‐F2t‐Isoprostane adverse effects on postischemic rat hearts
Authors: Xia Zhengyuan , Liu Hui‐min , Xia Zhong‐yuan , Liu Yanan , Lei Shaoqing , Mao Xiaowen , Irwin Michael G 
Published: June 2021

15‐F2t‐Isoprostane (IsoP), a specific marker of oxidative stress, is increased after myocardial ischemia. It exerts deleterious effects on postischemic myocardium. We hypothesized that IsoP exacerbates post‐ischemic myocardial injury by stimulating endothelin‐1 (ET‐1) production. Adult rat hearts were perfused by the Langendorff technique. Global myocardial ischemia was induced by stopping perfusion for 40 min followed by 60 min of reperfusion. Hearts were randomized to one of five groups: untreated (C), treated with IsoP (100 nM) or the ET‐1 receptor A/B antagonist bosentan (1 μM) alone or in combination 10 min prior to ischemia and for 15 min during reperfusion or treated with IsoP as above plus delayed bosentan administration 15 min after reperfusion. Coronary effluent ET‐1 levels in the IsoP group were higher than those in the C group during reperfusion accompanied with increased release of cardiac‐specific creatine kinase, reduced cardiac contractility and increased myocardial infarct size (all p<0.05 vs. C). Bosentan administration during early reperfusion exacerbated the IsoP deleterious effects while delayed administration attenuated it. It is concluded that IsoP‐induced ET‐1 production during later reperfusion is detrimental to functional recovery of damaged myocardium while ET‐1 increase during early reperfusion seems to improve it.Supported by NSFC grants (30872447 and 30672003)
Ginkgo Biloba Extract Ameliorates the Formation of Foam Cells by Regulating the Expression of SR‐A and ABCA1 in Macrophage: Role of Heme Oxygenase‐1
Authors: Su Kuo‐Hui , Tsai Jin‐Yi , Kou Yu Ru , Chiang An‐Na , Lee Tzong‐Shyuan 
Published: June 2021

ObjectiveAccumulation of foam cells in intima is the hallmark of early stage atherosclerotic lesion. Ginkgo Biloba extract (EGb761) has been reported to exert excellent anti‐oxidative and anti‐inflammatory properties in the development of atherosclerosis, yet the effect and the molecular mechanisms of EGb on the formation of macrophage foam cells are not fully understood.Methods and resultsTreatment with EGb761 resulted in a dose‐dependent decrease in oxLDL‐mediated cholesterol accumulation in macrophages, a result that was due to a decrease in cholesterol uptake and an increase in cholesterol efflux. Additionally, EGb treatment significantly decreased the mRNA and protein expression of class A scavenger receptor (SR‐A), while EGb had no effect on the expression of CD36, SR‐BI or ATP‐binding cassette (ABC) transporter G1. Furthermore, EGb increased the protein stability of ABCA1 by reducing calpain activity without affecting ABCA1 mRNA expression. Moreover, small interfering RNA (siRNA) targeting heme oxygenase‐1 (HO‐1) abolished the EGb‐induced protective effects on the expression of SR‐A and ABCA1 and calpain activity. Consistently, EGb‐mediated suppression on lipid accumulation in foam cells was also abrogated by HO‐1 siRNA.ConclusionEGb confers the protection from the formation of foam cells by an HO‐1‐dependent regulation on cholesterol homeostasis in macrophages.
Effects of a 4 Hour Exposure to Conventional Peritoneal Dialysis Fluids on the Murine Hepatic Microcirculation
Authors: Patrick Amanda , Fox‐Robichaud Alison E. 
Published: June 2021

Peritoneal dialysis (PD) is associated with structural and functional changes in the peritoneal and liver vasculature limiting its efficacy. Our objective was to examine the impact of high osmolar PD solutions and a 4hr dwell time on the liver microcirculation. Mice were given TNF 500ng or normal saline 50 μl (NS) IP, then 30 min later 2 ml of PD solution was injected. The hepatic microcirculation was examined by intravital microscopy. The PD fluids were a glucose‐based, bicarbonate buffered Physioneal, icodextrin‐based lactate and bicarbonate buffered Extraneal and dextrose‐based, lactate buffered Dianeal, compared to lactated Ringer's.In TNF‐treated mice, Dianeal and Extraneal caused an increase in leukocyte rolling, compared to NS (P>0.004). Adhesion was higher with TNF compared to NS in all groups (P>0.05); however, there was no significant difference between PD solutions. Comparing the 4 hr to a 1 hr dwell, Physioneal only was associated with a 6‐fold increase in adhesion (0.8±0.3 vs 5.2±0.7, P<0.001) and a decrease in leukocyte rolling (8.5±2.1 vs 3.2±0.8, P<0.04) with peritoneal TNF exposure.With a clinically relevant exposure time, TNF, combined with a glucose based, bicarbonate buffered PD solution, induced an increase in leukocyte adhesion in the hepatic microcirculation. Replacement with icodextrin may alleviate the effects of high glucose and cytokine stimulation.
Effects of high salt diet on age‐related hypertension and central AngII‐induced cardiovascular responses
Authors: Basgut Bilgen , Erdos Benedek , Whidden Melissa , Kirichenko Nataliya , Woods Mary , Tumer Nihal 
Published: June 2021

Angiotensin II (AngII) plays an important role in both age‐related and salt‐induced hypertension. The aim of this study was to investigate the effects of age and high‐salt (HS) diet on resting blood pressure (BP) and heart rate (HR), as well as on central AngII‐induced cardiovascular responses. Young (5 mo) and old (27 mo) male F344xBN rats were fed regular chow or HS (8%) for 11 days. BP and HR were measured using radiotelemetry. AngII (10ng/μl/h) or CSF was infused intracerebroventricularly before and during HS for 3 days with osmotic pumps. Old rats had significantly higher BP (108.3±3.6 mmHg) than young (96.1±3.1 mmHg, p<0.05). HS diet caused significant increases in BP in both young and old groups (young: 99.0±3.5, p<0.01; old: 116.3±4.1, p<0.001), but the increase in BP was significantly higher in old rats (p<0.05). In contrast, HR didn't change significantly in either group in response to HS diet. AngII‐induced BP increases were significantly diminished in old rats (4.4±2.0 %) compared with young (12.6±1.3%, p<0.05), while HR responses were similar (15.8±4.0% and 13.5±2.1%). HS diet enhanced AngII‐induced BP and HR elevations in both age groups, but BP increases in old rats (5.9±1.7%) were still significantly lower compared with young (18.8±8.1%, p<0.05). Our findings indicate that sensitivity of BP to HS diet increases with age, and that central AngII‐induced pressor responses are diminished in old rats compared with young both under control conditions and during HS diet treatment.Supported by the Medical Research Service of the Department of Veterans Affairs, by an award from the American Heart Association and by a TUBITAK scholarship.
Sex differences in the sympathetic balance of blood pressure: the role of the α‐adrenergic receptors
Authors: Hart Emma C , Charkoudian Nisha , Wallin B Gunnar , Roberts Shelly K , Johnson Christopher P , Joyner Michael J 
Published: June 2021

In men, muscle sympathetic nerve activity (MSNA) is positively related to total peripheral resistance (TPR) and inversely related to cardiac output (CO). However, this relationship was not observed in young women. We aimed to investigate whether simultaneous β‐adrenergic stimulation offsets this balance in young women. We measured MSNA (peroneal microneurography), arterial pressure (brachial line), CO (open‐circuit acetylene) and TPR before and after systemic β‐blockade with propranolol in 6 young normotensive women (age; 24 ± 2 yrs, body mass index; 23 ± 1 kg/m2). There was no difference in CO (5.7 ± 0.3 L vs. 5.3 ± 0.4 L), mean arterial pressure (MAP; 95 ± 3 mmHg vs. 95 ± 2 mmHg) before and after beta‐blockade. However, there was significant reduction in heart rate (HR; 61 ± 3 beats/min vs. 55 ± 2 beats/min, P<0.05). β‐blockade caused an increase in TPR (17.4 ± 1.2 mmHg/ml/min vs. 18.5 ± 1.3 mmHg/ml/min; P=0.07) and MSNA (28 ± 3 bursts/100hb vs. 33 ± 3 bursts/100hb, P=0.08). Before β‐blockade there was no relationship of MSNA to TPR, CO or MAP. Following β‐blockade, there was a positive relationship between TPR and MSNA (r=0.60). However, there was no relationship of MSNA to cardiac output (r = −0.12). Interestingly, MAP became related to MSNA (r = 0.56). In summary, the β‐adrenergic receptors appear to play a key role in the sympatho‐hemodynamic balance in young women.AHA 09POST2170087
Alternans of repolarization and depolarization in ventricular myocytes
Authors: Chourasia Sonam , Agarwal Anuj , Jing Linyuan , Patwardhan Abhijit 
Published: June 2021

Several studies suggest that repolarization alternans play an important role in initiation of ventricular arrhythmias. While alternans of duration of repolarization, i.e. of action potential duration (APD), has been extensively investigated, little is known about alternans of amplitude of action potentials (APA). The purpose of our study was to examine the relationship between APD and APA alternans and to determine potential mechanisms of APA alternans. Transmembrane potentials were recorded using glass micro‐electrodes in swine ventricular tissue (n=8). From 51 trials we observed that the incidence of APD alternans was 33% of all action potentials recorded for cycle lengths &*8804; 290 ms. Alternans of APA occurred 50% of times when APD alternans occurred and were concordant (long action potentials were also tall) 98% times. Incidence of APD alternans along with APA alternans was 78% with 96% concordance. These results show that occurrence of APA alternans is not rare. Alternans of APA were accompanied by alternans of |dv/dt|max 77 % of times, suggesting that sodium current may underlie alternans of APA. The potential effect of alternans of depolarization phase of the action potential on conduction suggests that this may also play a role in loss of electrical stability.Supported by the American Heart Association (Great Rivers Affiliate) and the National Science Foundation (CBET 07350).
Identification of the impact of contention on heart rate variability
Authors: Mongue‐Din Héloïse , Salmon André , Fiszman Marc Y , Fromes Yves 
Published: June 2021

Several methods allow monitoring electrocardiogram (ECG) in small animals. Sedation may help to maintain animals; however anaesthetic drugs impair the heart rate variability (HRV). Implantable telemetry devices allow experiments in freely moving animals; but this technique requires surgery and thus a prolonged recovering period is necessary prior to ECG recording. Contention is an alternative to these methods, provided a better understanding of its influence on HRV. This study aimed at investigating the impact of contention on some HRV parameters.Telemetric and restrained ECG of Syrian hamsters were performed with TA10ETA‐F20 sensors and the EasyCG system, respectively. Time domain analysis based either on statistical or autoregressive approaches showed no significant difference in HRV at baseline. Investigations in the frequency domain revealed that restrains influenced low frequencies, translating a higher sympathetic activity. Pharmacological assays confirmed that restraints affected the sympathovagal balance.In conclusion, the imprint of contention on HRV was consistent with a shift of the sympathovagal balance towards a higher sympathetic tone.Funding: Association Française contre les Myopathies
Isolation and characterization of lectins from the coronary luminal membrane
Authors: Perez‐Aguilar Sandra , Torres‐Tirado David , Ramiro‐Diaz Juan , Knabb Maureen , Rubio Rafael 
Published: June 2021

The luminal membrane of vascular endothelial cells is coated with a variety of proteoglycans, glycosaminoglycans, glycoproteins and glycolipids. These glycosylated structures sense alterations in flow stimuli to mediate myocardial responses. Several lectinic endothelial proteins, such as VCAM‐1, ICAM‐1, PECAM‐1, integrins, have been implicated in the response to flow, and other proteins that respond to flow have yet to be characterized as to their lectinic nature and include B2R, AT1R and the ENaC channels. To characterize the lectinic structures in guinea pig endothelial membranes, columns were produced with bound sugars of mannose, galactose or N‐ acetylglucosamine or a combination of the three sugars. The eluted lectin fraction was tested using dot blots with antibodies against flow‐sensitive proteins. The results show that approximately 10% of the eluted proteins loaded in columns with single sugar are lectins, and 15% of the protein loaded in the three sugar column are lectins. VCAM‐1, ICAM‐1, PECAM‐1 and ENaCs were all found in the eluent of individual sugars or a mix of the three sugars. These results suggest that there are important flow sensitive proteins that are lectinic in nature and present on the luminal surface of the vascular endothelium. Additionally, these results confirm the presence of lectinic ENaC channels in the endothelial glycocalyx.Funded by CONACyT SEP‐42567, CONACyT‐SALUD 2004‐C01‐156, Fulbright‐Garcia Robles 9583
Increased Urinary Renin Excretion Rate in Chronic Ang II‐infused Rats Fed a High Salt Diet leads to augmented urinary Ang II levels.
Authors: McCormack Michael , Liu Liu , Seth Dale M , Kobori Hiroyuki , Navar L Gabriel , Prieto Minolfa C 
Published: June 2021

This study examined the urinary excretion of renin (uRen), angiotensinogen (uAGT), and angiotensin II (uAngII) in chronic AngII‐infused Sprague‐Dawley rats fed a high salt (HS) diet. Three groups were studied: 1) AngII‐infused [80 ng/min, 14 d, n=5]; 2) AngII‐infused plus HS [Ang II+HS; 8% NaCl; n=4]; 5) AngII‐infused, HS plus an AngII type 1 receptor blocker (ARB) [Ang II+HS+Candesartan, 25 mg/L, drinking water, 14 d, n=5]. Systolic blood pressures increased in AngII (175±10 mmHg) and were augmented by HS in AngII+HS rats (222±8 mmHg). By day 13, uRen, uAGT and uAngII excretion rates increased in AngII‐infused rats, and in AngII+HS rats: [uRen (AngII: 9±3 vs. AngII+HS: 10±4 ×10‐5 Enzyme Units/day); uAGT (AngII: 1107±106 vs. AngII+HS: 4363±1673 ng/day); uAngII: (HS:1,851±327; AngII: 3,813±431; AngII+HS: 8,570±889 vs. NS: 2080±361 fmol/day; respectively)]. ARB treatment prevented these increases (uRen: 5±3×10‐5 Enzyme Units/day; uAGT: 240±28 ng/day; uAngII: 3,796±1,059 fmol/day). Thus, HS exacerbates the increases in uRen, uAGT, and uAngII as well as the systolic blood pressure in AngII‐dependent hypertensive rats.NIH [IdeA Program (P20‐RR‐017659‐06) and the Tulane‐BIRCWH Program (K12HD043451)]; and the AHA (09PRE2209079 and 09BGIA2280440).
INFLUENCE OF MATERNAL HIGH SODIUM DIET ON SYSTEMIC AND RENAL RENIN ANGIOTENSIN ALDOSTERONE SYSTEM OF MALES AND FEMALES OFFSPRING WISTAR RATS
Authors: Ramos Débora Rothstein , Costa Nauilo Lima , Jang Karen Lucasechi Lopes , de Oliveira Ivone Braga , Furukawa Luzia Naoko Shinohara 
Published: June 2021

Objectiveto evaluate the renin angiotensin system (RAS) of male and female offspring, which mothers received high sodium diet during pregnancy.Methods and Results (mean±SEM p<0.05 n=8/group)Female Wistar rats received normal salt diet (NSD 1.3%) or high salt diet (HSD 8.0% NaCl) during pregnancy. The offsprings (offNSD, offHSD), males (M) and females (F) were fed NSD until 12 week old. The blood pressure (mmHg) was lower in F (112±2.4) than M offHSD (120±2.4). Aldosterone (pg/mL) was higher in F offNSD (1005±153.3) and offHSD (988±210.2) compared to M offNSD (410±35.8) and offHSD (302±24.9) respectively. The plasma renin activity (ng/mL/h) was lower in M offHSD (2.2±0.6) than M offNSD (4.2±0.4). The renal renin activity (ng/mg tissue/h) was higher in M offHSD (16.4±1.8) than M offNSD (9.0±0.8); and it was lower in F (6.7±1.2) than M offHSD (16.4±1.8). The renin granules (%) was lower in M offHSD (38.4±4.2) than M offNSD (60.7±5.0), and in F offHSD (46.4±4.4) than F offNSD (65.8±4.2). The renin gene expression of renin (IDVrenin/β‐actin) in renal cortex (1.0±0.1) and medulla (0.6±0.06) was lower in M offHSD than M offNSD (1.5±0.2; 1.5±0.2 respectively).ConclusionMaternal HSD decreases systemic RAS and gene expression of renal renin in males but not females. Probably there is influence of estrogen in female offspring.Financial support: FAPESP
Evidence for Aldosterone‐mediated regulation of Na‐K ATPase in kidney proximal tubules
Authors: Parks Jason , Barati Michelle T , Salyer Sarah A , Mandal Amritlal , Klein Janet D , Khundmiri Syed J 
Published: June 2021

Recent investigations from several laboratories have shown MR expression and increased NHE3, NHE1, and NBCe1 activities in kidney proximal tubules (PT) after aldosterone (Aldo) stimulation. Non‐genomic effects of Aldo have been demonstrated in human kidney PT cells (HK‐2). We hypothesize that Aldo increases Na+/K+ ATPase (Na/K) activity in PT. In the present study we aim to 1) determine if MR is present in human and rat kidney PT 2) determine if Aldo regulates Na/K expression and activity in rat basolateral membranes 3) determine if Aldo increases Na/K subunit in human kidney PT cells. IHC analysis of human and rat kidneys showed presence of MR in PT. Adrenalectomy (ADX) resulted in decreased MR, Na/K, and NHE1 in PT and β and γ ENaC in DCT and CCD. Treatment with Aldo restored MR, Na/K, and NHE1 expression in PT and ENaC expression in DCT and CCD. In human kidney PT cells (HK2, HKC‐5,‐8, and ‐11) Aldo caused translocation of MR into nucleus. Aldo increased Na/K expression and activity in human kidney PT cells. The effects of Aldo on Na/K activity in human kidney PT cells was blocked by specific inhibitors of MR (spironolactone) and by 11β‐HSD inhibitor carbonexolone but not by a GR inhibitor (mifepristone). Treatment with Aldo resulted in decrease in intracellular pH in human kidney PT cells. These results suggest that Aldo may regulate Na/K and NHE1 expression and activity in human and rat kidney PT.Funded by VAMR and AHA
Defective cAMP‐dependent HCO3‐ Secretion Leads to Abnormal Mucus
Authors: Yang Ning , Garcia Mary Abigail S. , Quinton Paul M. 
Published: June 2021

Cystic fibrosis (CF) is a hereditary, fatal disease caused by a unique pathology that appears to begin with thick mucus that obstructs the lumina of hollow organs. In the present study, PAS‐AB Staining, morphometry, pH stat and mucus collection assay methods were used to investigate the formation of abnormal mucus in CF mouse small intestine. We found that in the wild type mouse small intestine, carbachol (100 μM, an intracellular Ca2+ mediated activator) induced goblet cell mucus release, but did not stimulate sustained HCO3− secretion. Whereas, forskolin (10 μM) + IBMX (100 μM) applied to activate intracellular cAMP‐mediated pathways did not have any detectable effect on goblet cell mucus release, but did induce sustained HCO3− secretion. With HCO3− in the basolateral solution, PGE2 (1 μM) + 5‐HT (10 μM), cAMP and Ca2+mediated activators, induced more mucus release from goblet cells in the presence than in the absence of HCO3−. In CF mouse small intestine, PGE2 (1 μM) + 5‐HT (10 μM) also stimulated goblet cell mucus release, but there was no significant difference in mucus releasing goblet cells with or without HCO3− in the basolateral solution. cAMP activated HCO3− secretion was missing in CF intestine. These results suggest that a defect in cAMP‐dependent HCO3− secretion, rather than in mucus release, leads to the abnormal mucus observed in CF mouse.Supported by Elizabeth Nash Memorial Fellowship