bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovarian Cancer Cell Exosome Interactions with Platelets: A role for the Novel Transmembrane Protein SUSD2
Authors: Rodezno Tania G. , Stein Sarah J. , Graber Katelyn N. , Hora Kirby A. , Madeo Marianna , Roetman Jess J. , Gubbels Jennifer AA. , Larson Mark K. 
Published: June 2021

Ovarian cancer (OvCa) is the deadliest gynecologic cancer and ranks as the seventh‐leading cause of cancer death among women. OvCa can metastasize without the aid of the circulatory or lymphatic system by traveling through the peritoneal fluid (ascites), adhering to the mesothelial lining, and spreading to neighboring organs. Furthermore, OvCa tumors can hijack platelets as a means to evade immune responses and medicinal therapies. Recently, a novel tumor cell surface protein, Sushi Domain Containing 2 (SUSD2), was correlated with increased OvCa survival rates, as well as lowered platelet adhesion. Given that OvCa tumor cells are bathed in relatively minimal levels of platelets in the ascites, we hypothesized that OvCa cells can interact with platelets distally via released exosomes, and that exosome‐platelet interaction can be inhibited by abundant SUSD2 presence on the tumor cells. To test this hypothesis, exosomes were harvested from OvCa‐derived cell line media supernatant, isolated via differential ultracentrifugation, and verified via Western blotting for exosome‐specific markers and flow cytometric gating on exosome‐sized cell particles. Exosomes derived from SUSD2‐knockdown cell lines were secreted at significantly higher amounts compared to cells with higher levels of SUSD2 expression. Similarly, exosomes from SUSD2‐knockdown cells had a more pronounced positive effect on agonist‐induced platelet activation as measured by GPIIb/IIIa integrin conformational activation, as well as increased platelet spreading on fibrinogen. The results suggest a mechanistic role of SUSD2 in OvCa exosome production and exosome‐platelet communication, and a link between cancer cell and platelet interaction that does not require proximal contact.Support or Funding InformationResearch was supported in part by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103443), as well as funding from the National Science Foundation/EPSCoR program [IIA‐1355423], the state of South Dakota, the Cynthia Ballentine‐Roesler Memorial Fund, and an undergraduate fellowship from the American Physiological Society.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Non‐invasive assessment of arterial stiffness correlates with age‐related vessel structure: a new Popmètre Device for Rats
Authors: Amaral Sandra Lia , Fabricio Mayara F. , Vidal Mateus R. , Ruiz Thalles F.R. , Zago Anderson S. , Vicentini Carlos A. , Jordão Maria T. , Michelini Lisete C. 
Published: June 2021

Arterial stiffness measurement, evaluated by pulse wave velocity (PWV), is a predictor of cardiovascular events. Among the main factors that affect arterial stiffness are cross‐sectional area, medial wall thickening and wall‐to‐lumen ratio. Recently, a device using finger‐toe pulse wave velocity was validated for humans study, but to better understand the mechanisms that change arterial stiffness, it is necessary to use the arterial vessel for genic, proteic and histological analysis. Therefore, a new device – popmètre® – was designed for measurements of PWV in animals and it was not validated yet. The aim of this study was to correlate the PWV using a new device for animal studies with vessel structure in rats of different ages. Forty‐two Wistar rats were allocated into 3 groups of different ages: Young: 1 month; Adult: 4 months and Older: 12 months. Two photodiodes were positioned on the right thoracic and pelvic members for PWV measurement, on anesthetized rats. Then, aorta, carotid, femoral and renal arteries were extracted and prepared for histological analysis (cross sectional area – CSA and wall thickness). Results of PWV and morphometric analysis were then correlated using Pearson correlation test. As expected, PWV was 46% higher in adult rats compared with young rats and 20% higher in aged rats compared with adult ones. Cross sectional area was significantly higher in aged rats compared with young rats in aorta (+151%), carotid (+94%), femoral (+62%) and renal (251%) arteries. Wall thickness was not altered among groups. A significant correlation was observed between CSA and PWV in all arteries: aorta (r=0.5642; p<0.001); carotid (r=0.6854 p<0.001); femoral (r=0.6642 p<0.001) and renal ( r=0.7817; p<0.0001). Wall thickness did not correlate with PWV. The results of this present study allow us to suggest that PWV measurement, obtained by a new device pOpmètri® for small animals, was able to detect age‐related vessel structure in rats.Support or Funding InformationSão Paulo Research Foundation (FAPESP) and Coordination for the Improvement of Higher Education Personnel (CAPES).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of Smooth Muscle, but not Endothelial, Mineralocorticoid Receptors Prevents Obesity‐Associated Coronary Vascular Dysfunction in Females
Authors: Brown Scott M. , Meuth Alex I. , Jaffe Iris Z. , Bender Shawn B. 
Published: June 2021

Coronary vascular dysfunction is an independent predictor of cardiac mortality in obesity and diabetes, both of which are associated with inappropriate activation of the renin‐angiotensin‐aldosterone system (RAAS). We recently demonstrated that systemic mineralocorticoid receptor (MR) blockade with spironolactone treats coronary vascular dysfunction in male Zucker Obese rat model. The aim of the present study was to investigate MR involvement in coronary dysfunction induced by western diet (WD) feeding in female mice, via both systemic blockade and using vascular cell‐specific MR knockout (KO) mice. Female C57BL/6J, endothelial cell (EC)‐specific MR KO mice, and smooth muscle cell (SMC)‐specific MR KO mice were fed either control diet or WD for 16 weeks. Systemic MR blockade was achieved in a group of WD fed C57BL/6J mice via spironolactone (Spiro; sc, 20 mg/kg/d) treatment for 16 weeks. Mice were 28–32 weeks of age at study completion. WD feeding induced obesity, hyperinsulinemia, hyperglycemia, glucose intolerance and adipose inflammation, but did not change blood pressure. Coronary vascular function was assessed via wire myography of left ventricular coronary arteries. Coronary endothelium‐dependent vasodilation to acetylcholine (ACh) was impaired by WD feeding and this was prevented by Spiro treatment and in SMC MR KO mice fed a WD, independent of blood pressure. Pretreatment of coronary arteries with the superoxide dismutase mimetic Tempol restored maximal dilation to ACh in WD fed mice. EC MR KO had no effect on coronary function in mice fed control diet or WD. Endothelium‐independent vasodilation to sodium nitroprusside was principally unaffected by WD feeding. Furthermore, in SMC MR KO mice, WD‐induced enhancement of coronary vasoconstriction to the thromboxane mimetic U46619 was prevented. Additional studies revealed that WD feeding increased gene markers of endothelial inflammation (ICAM‐1, PECAM) and fibrosis (collagen I) in aorta and that this is prevented in SMC MR KO mice fed a WD. SMC MR deletion did not, however, attenuate WD‐induced visceral adipose inflammation or glucose intolerance. Taken together, this study confirms and extends our previous findings regarding MR involvement in obesity‐associated coronary vascular endothelial dysfunction. Specifically, these data provide further insight into the mechanisms underlying the beneficial effects of MR antagonism in obesity, in particular highlighting a novel role of SMC MR, but not EC MR, as an important mediator in the development of obesity‐associated coronary vascular dysfunction.Support or Funding InformationFunded by VHA BLR&D BX002030 (SBB) and NIH NHLBI R01 HL119290 (IZJ).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Microarray Analysis of Long Noncoding RNAs in the Heart and Plasma of Type 2 Diabetic db/db Mice
Authors: Pant Tarun , Dhanasekaran Anuradha , Bosnjak Zeljko , Ge Zhi‐Dong 
Published: June 2021

ObjectiveDiabetic cardiomyopathy (DCM) refers to diabetes‐associated changes in the structure and function of the myocardium that is not directly attributable to other confounding factors such as coronary heart disease or hypertension. Long noncoding RNAs (lncRNAs) are emerging as the regulator of the development, proliferation, and aging of cardiovascular cells and the pathogenesis of cardiac hypertrophy and heart failure. Little is known regarding lncRNA expression profiles in DCM. The present study was to develop lncRNA expression profiles of the heart and serum of type 2 db/db mice with and without DCM and identify candidate genes for DCM.ResultsEchocardiography results indicate that there was no significant differences in the thickness of left ventricular wall, left ventricular end‐diastolic volume, the peak velocity of mitral E and A waves, isovolumic contraction time of the left ventricle, ejection time of the left ventricle, and myocardial performance index between type2 db/db mice and C57BL/6 controls at 6–8 weeks of age. Left ventricular end‐systolic volume was significantly increased, and ejection fraction and mitral E/A ratio were significantly decreased in db/db mice with DCM at 18–20 weeks of age compared with age‐matched controls. Profiling revealed differentially expressed (DE; adjusted P –value<0.05) lncRNAs in heart and plasma were 663 and 152 whereas the mRNA expressions in the same order were 447 and 127 of Wild type (C57BL/6, db/db) mice vs type 2 db/db (C57BL/6, db/db) whereas in the Wild Type old (C57BL/6, db/db) mice vs type 2 db/db with DCM (C57BL/6, db/db) total LncRNA and mRNA deregulated in heart were 816 and 662 whereas the mRNA expression in the same order were 662 and 2580.ConclusionDCM is associated with changes in global patterns of lncRNA expression. Our study lays the foundation for further studies defining the role of individual lncRNAs in the pathogenesis of DCM.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mitophagy Must Be Maintained at a Certain Level in Order to Provide Cardioprotection in Mice During Fasting
Authors: Bantis Katrina , Zhang Yawen , Kobayashi Satoru , Liang Qiangrong 
Published: June 2021

Previous literatures have shown a clear yet undefined relationship between caloric restriction, or fasting, and preserved cardiac function. Indeed, it has been demonstrated that fasting attenuates acute ischemic injury, chronic cardiac remodeling, and heart failure in mammalian models. Mitophagy, or mitochondrial degradation, has been implicated in mediating such cardioprotection, however the underlying molecular mechanism remains uncharacterized. Mitophagy plays a homeostatic role in mammalian cells, targeting excessive or damaged mitochondria for lysosomal degradation. Such degradation is essential in both dictating mitochondrial turnover during a cell's basal state as well as during times of stress when oxygen free radical species threaten a cell's ability to appropriately perform. We previously showed that one‐day fasting accelerated while two‐day fasting reduced mitophagy flux in the mouse heart, suggesting time‐differential effects of fasting on cardiac mitophagy. In the present study, we set out to determine if manipulating the level of mitophagy could mediate cardiac function during fasting. We subjected genetically altered transgenic (TG) mice with moderate‐ and high‐expression levels of Parkin, an E3 ubiquitin ligase that tags damaged mitochondria for degradation in order to promote mitophagy, in the heart as well as Parkin knockout (KO) mice and wild‐type (WT) mice to 48‐hours of complete caloric restriction. We then determined their cardiac function using echocardiography and invasive left ventricular (LV) catheterization. The results showed that 48‐hour fasting triggered cardiac dysfunction in WT mice, as indicated by significantly reduced heart rate, fractional shortening, maximal left ventricular pressure, and left ventricular contractility. Moreover, between the WT control (fed) and fasted KO mice, the latter group showed a significant reduction in these same cardiac parameters, suggesting that mitophagy is essential to the maintenance of cardiac function during fasting. Interestingly, between the WT control and the fasted TG mice which expressed moderate levels of Parkin, a significant change in cardiac function was not observed whereas significant cardiac dysfunction was observed between the WT control and TG mice that expressed high levels of Parkin. Taken collectively, our findings suggest that the downregulation of mitophagy under prolonged fasting mediates cardiac dysfunction and, thus, a specific level of mitophagy is required in order to be cardioprotective in mice.Support or Funding InformationThis study was supported by an NIH grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sodium Butyrate Attenuates Angiotensin II‐Induced Cardiac Hypertrophy by Inhibiting COX2/PGE2 Pathway via a HDAC5/HDAC6‐Dependent Mechanism
Authors: Zhang Linlin , Deng Mokan , Lu Aihua , Chen Yanting , Chen Yang , Wu Chunying , Wang Weidong , Tan Zhi , Yang Tianxin , Zhu Qing , Wang Lei 
Published: June 2021

Sodium butyrate (NaBu) is reported to play important roles in a number of chronic diseases. The present work is aimed to investigate the effect of NaBu on angiotensin II (Ang II)‐induced cardiac hypertrophy and the underlying mechanism in in vivo and in vitro models. Male SD rats were infused with vehicle or Ang II (200 ng/d) and oral administrated with or without NaBu (1g/kg/d) for two weeks and blood pressure was monitored by the telemetry system. After two weeks, cardiac hypertrophy parameters and COX2/PGE2 pathway were analyzed by Real‐time PCR, immunohistochemistry and Western blot. The content of ANP, PGE2 and activity of HDACs were measured by ELISA. The cardiomyocyte H9C2 cells were used to investigate the underlying mechanism by which NaBu inhibiting Ang II‐mediated hypertrophy. NaBu significantly attenuated Ang II‐induced increase in the mean arterial pressure from 159 ±8 mmHg to 127 ± 7 mmHg (P<0.01). Ang II treatment remarkably increased cardiac hypertrophy as indicated by increased ration of heart weight/body weight and enlarged cardiomyocyte size, extensive fibrosis and inflammation, as well as enhanced expresssion of hypertrophic markers, whereas hearts from NaBu treated rats exhibited a significant reduction in these hypertrophic responses. Mechanistically, NaBu suppressed the expression of COX2/PGE2 along with the production of ANP and phosphorylated ERK (pERK) stimulated by Ang II in vivo and in vitro, which is mediated by the inhibition of HDAC5 and HDAC6 activities. Additionally, expression knockdown of HDAC5 and HDAC6 via gene editing strategy dramatically blocked the hypertrophic response of COX2/PGE2 pathway induced by Ang II in vitro. These results provide solid evidence that NaBu attenuates Ang II‐induced cardiac hypertrophy by inhibiting the activation of COX2/PGE2 pathway in a HDAC5/HDAC6‐dependent manner.Support or Funding InformationNational Natural Science Foundation of China (No. 81600322, No. 81770707, No. 81603587)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Circulating transcriptome as a signature for the diagnosis of pulmonary arterial hypertension.
Authors: Qi Xinshuai , Gonzalez‐Garay Manuel J. , Vanderpool Rebecca , Song Shanshan , Tang Haiyang , Ayon Ramon J. , Desai Ankit , Yuan Jason X.‐J. 
Published: June 2021

IntroductionPulmonary Arterial hypertension (PAH) is a rare disease that progressively leads to right heart failure and risk of mortality. However, the diagnosis of PAH in clinic largely depends on hemodynamic data. Circulating transcriptomic profiles have been developed as biomarkers in multiple cardiovascular diseases and thus can be potentially used to detect the signature of PAH. Here we aim to develop a robust approach for the diagnosis and prediction of PAH and its severity by integrate genotype, phenotype, and gene expression data.MethodsWe analyzed 96 peripheral blood mononuclear cell transcriptomes from PAH patients and control cohort. Gene expression analysis was performed using Rsubread, limma, and EdgeR package in R. Variation calling, filtering. The comparison was performed between PAH, idiopathic PAH with control, and different PAH severity groups. GWAS was performed using Samtools, Vcftools, and PLINK.ResultsA total of 72 genes with significant differential expression and 150 genes associated with PAH severity were identified. In addition, 405 of the 4.1 million identified SNPs are associated with PAH.ConclusionCirculating transcriptome can be used to identify genetic signatures for the diagnosis of pulmonary arterial hypertension based on our preliminary results. Once validated in a larger cohort, the identified genes and SNPs can provide a molecular marker system for the PAH diagnosis in addition to hemodynamic data.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute Effect of Aerobic Exercise on Carotid Strain in Individuals with Multiple Sclerosis
Authors: Grigoriadis Georgios , Rosenberg Alexander J. , Wee Sang Ouk , Schroeder Elizabeth C. , Griffith Garett , Baynard Tracy 
Published: June 2021

INTRODUCTIONIndividuals with multiple sclerosis (MS) have increased arterial stiffness, a known risk factor for cardiovascular disease. Acute aerobic exercise is a stressor affecting markers of arterial stiffness, such as carotid strain (CS) and beta stiffness index, which provides insight into aspects of arterial function. Individuals with MS may have different responses to exercise compared to healthy individuals due to arterial dysfunction, which can be evaluated via markers of arterial stiffness.PURPOSETo evaluate the acute effect of aerobic exercise on CS in individuals with MS.METHODSSixteen individuals with MS (42 ± 8 yrs; 27.5 ± 6.9 kg/m2) underwent treadmill walking at 60% of their peak aerobic capacity for 20 min. Images of the carotid artery were obtained in the radial view with ultrasonography at baseline, immediate and 30 min post‐exercise. Speckle tracking software was used to calculate the following variables of arterial function: CS, CS time to peak (TPK), CS rate, CS rate TPK, radial velocity (RV), RV TPK, radial displacement (RD) and RD TPK. Carotid systolic blood pressure (cSBP) was measured via applanation tonometry and longitudinal carotid beta stiffness index via ultrasonography.RESULTSSee Table. CS rate, RV and carotid systolic blood pressure (cSBP) increased immediate post‐exercise (p<0.05). CS TPK and RD TPK decreased immediately post‐exercise and RD TPK remained decreased at 30 min post‐exercise (p<0.05). HR and beta stiffness index increased immediately post‐exercise (p<0.05) and returned to baseline at 30 min (p>0.05).CONCLUSIONThe baseline levels of CS in individuals with MS are lower than values reported for middle‐aged adults in the literature, indicative of baseline arterial dysfunction. Beta stiffness index increased immediately after exercise. While CS rate increased after exercise in individuals with MS similar to beta stiffness index, the difference disappeared after statistically controlling for HR. Our results suggest that individuals with MS do not improve arterial stiffness with acute aerobic exercise, providing more evidence for arterial impairment.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Sex and Exercise Intensity on Acute Flow‐Mediated Dilation Response to Aerobic Exercise in Healthy Young Adults
Authors: Kim Han‐Kyul , Hwang Chueh‐Lung , Lim Jisok , Yoo Jeung‐Ki , Perez Hannah , Handberg Eileen M. , Christou Demetra 
Published: June 2021

Brachial artery flow‐mediated dilation (FMD), a measure of endothelial function, is an independent predictor of future cardiovascular events. Sex and exercise intensity influence the acute FMD response to aerobic exercise in older adults, but in young adults this has not been investigated. Therefore, the purpose of this study was to compare the acute FMD response to a single bout of high‐intensity interval training (HIIT), moderate‐intensity continuous training (MICT) and low‐intensity continuous training (LICT) in young men vs. women. Twenty‐eight healthy young adults (14 men and 14 premenopausal women, 21.2±0.3 vs. 21.5±0.8 years of age, means ± SE, P =0.7) participated in this randomized crossover study. Brachial artery FMD was measured in response to reactive hyperemia following 5‐min forearm occlusion using high resolution ultrasonography. FMD measures were obtained prior to exercise, at the end of a single bout of HIIT (40 min, 4 × 4‐min intervals at 90% peak heart rate (HRpeak), MICT (47 min, 70% HRpeak) and LICT (47 min, 50% HRpeak) on the treadmill and following 60‐min recovery from exercise. The acute FMD response was influenced by exercise intensity but not sex (P=0.006 for exercise intensity × time and P=0.9 for sex × exercise intensity × time), thus the results are presented for men and women combined. FMD was attenuated by 20.7% following the end of HIIT (6.96±0.51 vs. 5.47±0.48%, pre‐ vs. end of exercise; P=0.001) and returned to pre‐exercise levels following 60‐min recovery (P>0.99). However, FMD did not change in response to MICT(7.10±0.53 vs. 6.32±0.57 vs. 7.26±0.37%; P≥0.3) and LICT (7.14±0.41 vs. 7.46±0.56 vs. 7.15±0.43%; P>0.99). In conclusion, exercise intensity, but not sex, significantly impacts the acute FMD response to aerobic exercise in young adults.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.