tbuckley/cabot-search huggingface dataset:
Abstract 15252: Ischemic-Trained Monocytes Improve Arteriogenesis During Hindlimb Ischemia
Authors: Gustavo Falero-Diaz, Catarina d Barboza, Felipe Pires, Roberto I Vazquez-Padron, Omaida C Velazquez, Roberta M Lassance-Soares
Journal: Circulation (2020)

Introduction: Recent studies have shown that innate response can build immunological memory. This process called “trained immunity” is an epigenetic reprogramming of the monocytes driven by a metabolism shift towards glycolysis. Hypothesis: Since HIF-1a is a major player in monocytes activation and also targets some epigenetic enzymes, we hypothesize that hypoxia/ischemia can lead to “trained immunity” improving arteriogenesis in a mouse model of hindlimb ischemia. Methods: Mice subjected to a unilateral single ischemia insult for 24hours (24h group: femoral artery ligation for 24 h) or by ischemia reperfusion cycles (Cycle group: ischemia-reperfusion in 4 cycles of 5 minutes) or non-ischemia (sham group), were used as donors in the monocyte transfer experiment. Recipient mice underwent to permanent hindlimb ischemia one day prior the tail vein injection of bone marrow (BM) monocytes from the ischemic leg. Laser Doppler assessed blood flow recovery before and after hindlimb ischemia. Arteriogenesis was quantified on recipient mice by assessing the diameter of gracilis collaterals. A 24h group monocytes from ischemia and non-ischemia leg was used as donors to test the systemic vs. local effect of the ischemic-trained monocytes. Lin- cells were used as a control. Cultured human monocytes were subjected to 24h hypoxia and gene expression for epigenetic enzymes was performed by real time rt-PCR Results: Blood flow recovery in recipients who received ischemic-trained monocytes (24h and cycle) improved overtime compared to sham. Arteriogenesis was significant greater in 24h group compared to sham. Surprisingly, the improvement in blood flow recovery was abolished using combined monocytes from ischemic and non-sichemic, suggesting that ischemia training has a local effect in the monocytes. The Lin- experiment confirmed that the ischemia training is monocyte specific. Moreover, hypoxia regulated epigenetic enzymes responsible for histones methylation in human monocytes. Conclusions: Monocytes can be trained by previous ischemia/hypoxia insult and improve arteriogenesis during hindlimb ischemia. The molecular mechanisms that lead the trained immunity by hypoxia still unknown, however epigenetic modifications might play a role in this process.
Abstract 16116: Chronic Kidney Disease in HIV Population and Cardiovascular Disease
Authors: Bertrand Ebner, Jelani Grant, Louis Vincent, Quentin Loyd, Catherine Boulanger, Alexis Powell, Barry E Hurwitz, claudia Martinez
Journal: Circulation (2020)

Background: Chronic kidney disease (CKD) is well known to increase the risk of cardiovascular disease (CVD). However, there is limited knowledge about the association between CKD in persons living with HIV (PLWH) and CVD. We sought to investigate the prevalence and characteristics of CVD in PLWH with and without CKD at a large single center in South Florida. Methods: A retrospective chart review of 985 of PLWH from a Special Immunology clinic at a large center in South Florida between 2017-2019 was performed. Data on demographics, clinical, laboratory and diagnostic studies were obtained from electronic health records. Results: The prevalence of CKD in PLWH in our cohort was 11%. The group of CKD was older (58 vs. 51 years p&lt;0.05), with significantly more men (66% vs. 53% p=0.012). The CKD cohort had increased rates of hypertension, coronary artery disease (CAD), heart failure, diabetes mellitus, and cerebrovascular disease (&lt;0.05 for all). PLWH with CKD had a significantly higher HbA1C level, systolic and diastolic blood pressure, statin use, and lower LDL-C (p&lt;0.05 for all). Subjects with HIV and CKD had a higher rate of cardiac catheterization (7.2%), with an increased rate of obstructive CAD (6.3%), when compared to PLWH without CKD (1.3% and 0.7%, respectively, p&lt;0.05 for both). The rate of diastolic dysfunction was significantly higher in PLWH with CKD than those without CKD (p=0.004), although, no difference in ejection fraction (p=0.079) was noted. We found a significantly lower average CD4 count in individuals with HIV and CKD compared to those without CKD (483 ± 297 cells/mm 3 vs. 570 ± 342 cells/mm 3 , p=0.006). No significant difference was noted between groups in mean viral load, proportion with undetectable viral load, and use of antiretroviral medications. Prevalence of chronic hepatitis infection (B and/or C) was also higher in the CKD cohort (p&lt;0.05). Conclusion: In this study, we found a comparable rate of CKD compared to age-matched patients from the general population. We found higher rates of traditional CVD risk factors and disease in the CKD cohort, without significant difference in HIV-related factors. This supports the importance of CVD risk factor optimization in this population.
Abstract P080: Lifetime Trauma Is Associated With Elevated Blood Pressure In Middle-aged And Older Latinas
Authors: Danny Vo, Billy A Caceres
Journal: Circulation (2021)

Introduction: Latina women are more likely than non-Latina White women to have uncontrolled and undertreated hypertension. Prior research suggests greater exposure to traumatic experiences (such as interpersonal violence) is associated with elevated blood pressure and higher cardiovascular disease risk in women. However, few studies have investigated these associations among Latina women, a population that is at increased risk for hypertension. The purpose of this pilot study was to fill knowledge gaps by examining the associations of lifetime trauma (including childhood and adulthood) with blood pressure in middle-aged and older Latinas. Hypothesis: We assessed the hypothesis that lifetime trauma is associated with elevated blood pressure in middle-aged and older Latinas. Methods: Participants were recruited from an existing study in New York City called the Washington Heights/Inwood Comparative Effectiveness Research Project. Data collection consisted of a questionnaire administered by a research coordinator and in-office assessment of two blood pressure readings using recommended guidelines. The average systolic and diastolic blood pressures were calculated from these two measurements. Lifetime trauma was assessed with the Life Events Checklist which assesses 17 potentially traumatic experiences. We summed responses to the Life Events Checklist to create a count of lifetime trauma. Posttraumatic stress disorder (PTSD) symptoms were assessed with the PTSD Checklist-Civilian Version that assess presence and severity of 17 PTSD symptoms in the last month. We used linear regression models to separately examine the associations of lifetime trauma with systolic and diastolic blood pressure adjusted for demographic characteristics, health behaviors, PTSD symptoms, sociocultural factors (such as discrimination and acculturation). Results: The final sample included 50 Latina women (ages 42-77, mean=63.1 [9.7]). All women reported at least one traumatic experience with an average of 4.8 traumatic experiences in their lifetimes (range 1-10). A higher count of lifetime trauma (B [SE] = 5.56 [2.63], p = 0.04) was positively associated with greater systolic blood pressure in adjusted regression models. Although women who reported a higher count of lifetime trauma had higher diastolic blood pressure, this association was not statistically significant (B [SE] = 2.14 [1.67], p = 0.21). Conclusion: Findings indicate a higher count of lifetime trauma is associated with elevations in systolic blood pressure among Latina women. This is consistent with results of studies that have examined associations of lifetime trauma with blood pressure among women in the general population. There is a need for larger studies that incorporate longitudinal designs to investigate the associations of trauma and other sociocultural factors with blood pressure among Latina women.
Abstract 15602: Sex-differences in Extreme Exercise-induced Adverse Cardiovascular Remodeling
Authors: Gemma Sanguesa, Aline Meza, Anna Alcarraz, Cira Rubies, Lluis Mont, Montserrat Batlle, Eduard Guasch
Journal: Circulation (2020)

Introduction: There is emerging evidence in men that sustained high-intensity training promotes an adverse cardiovascular remodeling, thereby increasing the risk of atrial fibrillation, ventricular arrhythmias and coronary calcification. Whether men and women are similarly affected by high intensity exercise-induced harm is unclear. Our aim was to study sex differences in a long-term endurance training rat model. Methods: Male and female Wistar rats were subjected to high intensity training for 16 weeks (INT, 60min 60cm/s, male n=20, female n=15). Sedentary rats (SED, male n=20, female n=18) were used as controls. At the end of the training period, rats had an electrocardiogram and echocardiography performed. Vascular fibrosis was assessed in descending aorta, left carotid, and intramyocardial arteries (IMA), right and left atria, and left ventricle (LV) histological samples. mRNA levels of cardiac hypertrophy, fibrosis, oxidative stress and inflammation genes were assessed in LV samples by Real-Time PCR. Results: INT male rats presented lower heart rate (382±9, 340±10, SED vs INT, p&lt;0.01) and a longer QRS duration (18.8±0.6, 22.4±1.1, SED vs INT, p&lt;0.01), while these were not modified in the INT female group. Echocardiography showed eccentric LV hypertrophy in both trained male and female rats. High intensity exercise induced fibrosis in the descending aorta and carotid in both males and females, but IMA were only affected in trained male rats. In the heart, exercise-induced atrial fibrosis similarly occurred in both trained male and female rats. No training-induced fibrosis was evident in the LV of both INT male and female rats. Regarding LV mRNA analysis, INT males showed a reduction of desmin, TTN and N2BA/N2B ratio, whereas INT females exhibited higher desmin mRNA levels and lower αMHC/βMHC ratio. Intense exercise did not increase LV mRNA levels of fibrosis, oxidative stress and inflammation markers neither in males nor in females. In comparison to males, females had lower LV myocardial fibrosis as well as lower fibrosis markers. Conclusions: Male and female rats exhibit qualitatively different cardiovascular remodeling after extreme exercise. Nevertheless, both sexes might develop exercise-induced adverse vascular and cardiac effects.
Prognostic Value of Natriuretic Peptides and Cardiac Troponins in COVID-19
Authors: Jonathan W. Cunningham, Brian L. Claggett, Karola S. Jering, Muthiah Vaduganathan, Ankeet S. Bhatt, Ning Rosenthal, Scott D. Solomon
Journal: Circulation (2021)

iven the variable severity of coronavirus disease 2019 (COVID-19), clinicians need biomarkers that identify high-risk patients at the time of hospitalization.While elevated troponin is associated with greater mortality in COVID-19, 1,2 studies of natriuretic peptides (NPs) have been inconclusive. 2,3e investigated the independent prognostic value of NPs and troponin in COVID-19 inpatients discharged (alive or dead) between April 1 and November 30, 2020, with laboratory data in Premier Healthcare Database (n=48 510).COVID-19 infection, comorbidities and outcomes were defined using the International Classification of Diseases, Tenth Revision codes.Only biomarkers at admission (days 1 or 2) were considered.Associations between biomarkers and in-hospital death were assessed by logistic regression, adjusted for 18 covariates: age, sex, race/ethnicity, month, region, obesity, chronic renal/pulmonary disease, diabetes, hypertension, smoking, cancer, and 6 cardiovascular conditions (heart failure, myocardial infarction, peripheral vascular and cerebrovascular disease, valve disease, and atrial fibrillation).Supporting data are available to qualified researchers from Premier.The Mass General Brigham Institutional Review Board approved the study.NPs were available in 12 252 (25%) patients, and were analyzed in 4 groups: ≤35, 36 to 100, 101 to 400, and >400 pg/mL for BNP (B-type natriuretic peptide) and ≤100, 101 to 200, 201 to 1500, and >1500 pg/mL for NT-proBNP (N-terminal pro-B-type natriuretic peptide).Patients with higher NPs were older (mean, 74 years of age in the highest group vs 54 years of age in the lowest) and more likely to have heart failure (61% vs 5%) and atrial fibrillation (46% vs 5%).Adjusted risk of death was markedly greater in the highest versus lowest NP group
Site-specific glycoproteomic analysis revealing increased core-fucosylation on FOLR1 enhances folate uptake capacity of HCC cells to promote EMT
Authors: Li Jia, Jun Li, Pengfei Li, Didi Liu, Jing Li, Jiechen Shen, Bojing Zhu, Chen Ma, Ting Zhao, Rongxia Lan, Liuyi Dang, Wang Li, Shisheng Sun
Journal: Theranostics (2021)

Rationale: Epithelial-mesenchymal transition (EMT) has been recognized as an important step toward high invasion and metastasis of many cancers including hepatocellular carcinoma (HCC), while the mechanism for EMT promotion is still ambiguous. Methods: The dynamic alterations of site-specific glycosylation during HGF/TGF-β1-induced EMT process of three HCC cell lines were systematically investigated using precision glycoproteomic methods. The possible roles of EMT-related glycoproteins and site-specific glycans were further confirmed by various molecular biological approaches. Results: Using mass spectrometry-based glycoproteomic methods, we totally identified 2306 unique intact glycopeptides from SMMC-7721 and HepG2 cell lines, and found that core-fucosylated glycans were accounted for the largest proportion of complex N-glycans. Through quantification analysis of intact glycopeptides, we found that the majority of core-fucosylated intact glycopeptides from folate receptor α (FOLR1) were up-regulated in the three HGF-treated cell lines. Similarly, core-fucosylation of FOLR1 were up-regulated in SMMC-7721 and Hep3B cells with TGF-β1 treatment. Using molecular approaches, we further demonstrated that FUT8 was a driver for HGF/TGF-β1-induced EMT. The silencing of FUT8 reduced core-fucosylation and partially blocked the progress of HGF-induced EMT. Finally, we confirmed that the level of core-fucosylation on FOLR1 especially at the glycosite Asn-201 positively regulated the cellular uptake capacity of folates, and enhanced uptake of folates could promote the EMT of HCC cells. Conclusions: Based on the results, we proposed a potential pathway for HGF or TGF-β1-induced EMT of HCC cells: HGF or TGF-β1 treatment of HCC cells can increase the expression of glycosyltransferase FUT8 to up-regulate the core-fucosylation of N-glycans on glycoproteins including the FOLR1; core-fucosylation on FOLR1 can then enhance the folate uptake capacity to finally promote the EMT progress of HCC cells.
Abstract 14833: The Association Between Cardiovascular Disease Knowledge and Risk Factors Among African American Breast Cancer Survivors in the Deep South
Authors: Michelle S Williams, Chizoba Anyimukwu
Journal: Circulation (2020)

Introduction: African American breast cancer survivors in the Deep South have a disproportionately high burden of cardiovascular disease (CVD) mortality. This is due, in large part, to multiple potentially modifiable CVD risk factors that are disproportionately high in this group, such as high blood pressure, obesity, and poor dietary habits. The purpose of this study was to assess the association between CVD risk factors and heart disease knowledge among African American breast cancer survivors in the Deep South. Hypothesis: We hypothesize that the key CVD risk factors (smoking, BMI, physical activity, healthy diet, total cholesterol, blood pressure, and blood sugar) will be positively associated with heart disease knowledge score. Methods: The Heart Disease Knowledge Questionnaire was used to assess the participants’ knowledge of heart disease and heart disease risk factors. Questions from My Life Check were used to assess the participants CVD risk factors. Multivariate regression analyses were performed to determine which CVD risk factors and demographic characteristics can predict the participants’ heart disease knowledge score. Results: Seventy African American breast cancer survivors living in the Deep South enrolled in the study. A research team member administered the questionnaires over the phone. The mean age of the participants was 56.76 years (± 10.36) and 42.9% had a college degree or higher level of education. Results of a multivariate regression analysis showed that the number of healthy diet score components was the only cardiovascular health metric that was statistically significantly associated with heart disease knowledge score (p = .01). Education level was the only demographic characteristic that was statistically significantly associated with heart disease knowledge score (p = .004). Conclusions: Our results indicate that women with more knowledge of heart disease and higher levels of education are more likely to have better cardiovascular health metrics. Our findings underscore the need to disseminate and implement health education interventions aimed at increasing knowledge of modifiable CVD risk factors that are targeted towards African American breast cancer survivors in the Deep South.
Abstract 15541: Novel Molecular Entity for Effective Cardiac Regeneration: 5’ppp Microrna Induces Reprogramming and Accelerates Cardiomyocyte Maturation
Authors: Jiabiao Hu, Conrad Hodgkinson, Syeda S Baksh, Richard E Pratt, Victor J Dzau
Journal: Circulation (2020)

We have shown that miR combo directly reprograms fibroblasts into cardiomyocytes. However, both in vitro and in vivo, the generated cardiomyocytes are immature. Recently, we discovered that cardiomyocyte maturation is enhanced by NFkB activation. While miR combo initiates reprogramming, the effect on NFkB activity is modest. Therefore, miR combo only has a modest effect on maturation. We have now made an important discovery that 5’triphosphorylation (5’ppp) of RNA molecules markedly enhance NFkB activation; leading to increased and accelerated maturation of reprogramed cardiomyocytes. The addition of 5’ppp-RNA increased the number of mature cardiomyocytes by 4-fold (N=5, P&lt;0.05). Moreover, 5’ppp-RNA also accelerated the appearance of mature cardiomyocyte mRNAs (1 day after transfection vs 4 days for unmodified RNA). Importantly, these effects were lost when the 5’ppp moiety was removed. Knockdown studies suggest that 5’ppp-RNA binds to the Pattern Recognition Receptor Rig1. MNase-seq and ChIP-seq analysis suggests that 5’ppp-RNA activates YY1 (N=4, P&lt;0.001). We next asked if 5’ppp modification of the miRNAs within miR combo would also enhance cardiomyocyte maturation; thus, providing a single molecular entity that can initiate reprogramming and accelerate maturation of cardiomyocytes. Indeed, 5’ppp modification of the miR combo miR-1 increased the expression of the mature cardiomyocyte markers Actn2 (4-fold, N=3, P&lt;0.05) and Myh6 (4-fold, N=3, P&lt;0.05). In conclusion, 5’ppp-miR combo is a novel approach that has the advantage of both initiating reprogramming and accelerating cardiomyocyte maturation and should lead to more effective cardiac regeneration and restore cardiac function.
Fc-fused IL-7 mobilizes long-term HSCs in a pro-B cell-dependent manner and synergizes with G-CSF and AMD3100
Authors: Sora Kim, Young-Min Kim, Hyekang Kim, Yeon-Woo Kang, Subin Park, Sang-In Yang, Donghoon Choi, Young Chul Sung, Seung-Woo Lee
Journal: Leukemia (2021)
Abstract 16216: Increases in Renal Nkcc2 and Ncc Preceded the Elevation of Blood Pressure in Mice Treated With Clozapine
Authors: Zhiyun Ren, Laureano D Asico, Xiaoyan Wang
Journal: Circulation (2020)

One of major side effects of clozapine, a common antipsychotic drug, is hypertension. In order to explore the pathogenesis of the drug-induced hypertension, we examined the renal sodium transport proteins and BP in the C57Bl6/J male mice treated with clozapine at different doses for 1 week. Clozapine at 20mg/kg/day via osmotic mini-pump increased SBP ( 110±0.6,mmHg, femoral artery, under anesthesia) and DBP (76.7±1) relative to vehicle (97.6±1.2/71.2±2.7) while the renal protein expression of NKCC2 (180±21, % of vehicle) and NCC (171±22), and ENaC-α (140±7), β(166±21) and γ(130±7) was increased without changes in NHE3 and α1-NKA (n=5/group). Clozapine at lower doses (5&amp;10mg/kg/day,IP) did not change the conscious SBP and DBP monitored daily by tail-cuff, even on day 7 in 5 mg/kg group (115.61±1.6/90.1±1.3) and in 10mg/kg group (116.8±2/89.0±1.6) relative to vehicle (111.9±1.5/86.9±1.4) (n=4/group). Urinary excretion of Na + &amp; K + and serum concentrations of Na + , K + , Cl - , creatinine were similar in all groups. However, renal protein expression of NKCC2 was increased in 5mg/kg (360±80, % of vehicle) and 10mg/kg (247±50) groups; NCC was increased at 5 mg/kg (175±9); α1-NKA was increased in 5mg/kg (216±5) and 10mg/kg (163±2) groups. No increases were found in the protein expression of NHE3 and ENaCs. Those increases in renal NKCC2 &amp;NCC at 5 &amp; 10 mg/kg were consistent with those at 20 mg/kg. AT1R was increased at 5 (221±20) &amp;10mg/kg (255±21) while renin (186±15) and ACE1 (186±5), not ACE2, were increased at 5 mg/kg suggesting an activation of RAAS in kidney. NOX4, not NOX2, was increased at 5 mg/kg (453±69) while NOS3, not NOS1&amp;2, was decreased at 5 (60±21) and 10mg/kg (64±5) groups. TNFα, not IL-6 was increased at 5 (222±18) &amp;10 mg/kg (321±26). In cultured mouse distal convoluted tubule cells, clozapine also increased NCC and α1-NKA at 1nM (169±4;156±7) and 10nm(175±23;183±15) respectively ( 24h,n=4/group). Those changes in kidney, including increases in sodium transport proteins, RAAS components, ROS generation enzymes, inflammation factors and decrease in NO synthase, preceded the elevation of BP suggesting that direct or indirect regulations of clozapine on those proteins may play an important role in the pathogenesis of the drug-induced hypertension.