bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 110: Association of Blood Pressure Phenotype With Measures of Target Organ Damage
Authors: Urbina Elaine M , Ferguson Michael , Lande Marc , Meyers Kevin , Samuels Joshua , Flynn Joseph T
Published: September 2019

Ambulatory hypertension (HT) and masked hypertension (MH, normal in clinic, high on ambulatory BP monitoring, ABPM) are associated with target organ damage (TOD) in adults, while white coat hypertension (WC, high in clinic, normal on monitor) is felt to be benign. We sought to determine if BP phenotype is associated with TOD in youth. We measured casual BP, ABPM, adiposity, LV mass index (LVMI), systolic and diastolic function (E/e’ ratio) and pulse wave velocity (PWV) in 365 adolescents (15.6 + 1.7 years, 63% white, 58% male). BP phenotype was determined by mean of 6 casual aneroid SBPs, and 24-hour SBP on ABPM (Spacelabs Inc., Snoqualmie, WA) by age, sex and height specific pediatric cut-points (normotensive, NT=224; WC=90; MH=23; HT=28). ANOVA was used to evaluate differences in CV risk factors and TOD across ABP phenotypes. General linear models were used to determine if BP phenotype was an independent predictor of TOD after adjusting for age, demographics, and adiposity. There were no differences in age, race/ethnicity. MH had more females, HT were heavier than NT. There was no difference in dipping but 24-hour SBP load (%readings above 95
th
%ile) increased across groups (NT=12, WC=18, MH=55, HT=64, p≤0.02). There was no difference in LVM index (NT=31.8, WC=33.5, MH=32.6, HT=33.1 g/m
2.7
). WC had reduced strain compared to MH (-19.5 vs -23%). There were significant differences in diastolic function, and arterial stiffness. BP phenotype remained a significant determinant of E/e’ and PWV after adjustment for age, sex and BMI z-score (p≤0.0006). We conclude that 24-hour BP phenotype adds to prediction of diastolic dysfunction and arterial stiffness but not LVMI or systolic function.
Abstract 120: Protective Role of Vascular Smooth Muscle Rho-Related BTB Domain Containing Protein 1 in Hypertension and Arterial Stiffness
Authors: Fang Shi , Mukohda Masashi , Wu Jing , Nair Anand R. , Liu Xuebo , Lu Ko-Ting , Davis Debbie R. , Quelle Frederick W. , Sigmund Curt D.
Published: September 2019

Rho-related BTB domain containing protein 1 (RhoBTB1) is an atypical GTPase associated with human hypertension. RhoBTB1 was decreased in aorta from mice expressing a hypertension (HT)-causing PPARγ mutation (P467L) specifically in vascular smooth muscle (VSM, S-P467L mice). Restoration of VSM RhoBTB1 improved vasodilation, reversed arterial stiffness and HT by suppressing phosphodiesterase 5 (PDE5) activity. Here we sought to reveal the molecular function of RhoBTB1 and study its protective role in Angiotensin II (Ang II) induced hypertension. PDE5 and RhoBTB1 reciprocally co-immunoprecipitated in HEK293 cells; and notably, endogenous Cullin3 from HEK293 cells was also present in RhoBTB1/PDE5 immunoprecipitant. Whereas, RhoBTB1 was not sufficient to inhibit PDE5 activity
in vitro
(1.9±0.2 vs 1.7 ±0.2 nmol/min/mg, n=3), it was required for PDE5 ubiquitination in HEK293 cells. RhoBTB1-mediated PDE5 ubiquitination was blunted by pan-Cullin inhibitor MLN4924 treatment, and MLN4924 increased PDE5 activity in aorta. Thus, RhoBTB1 serves as a substrate adaptor for Cullin3-Ring ubiquitin ligase (CRL3) complex. Like mutation in PPARγ, Ang II infusion also reduced aortic RhoBTB1 expression. We generated mice with VSM specific, tamoxifen inducible RhoBTB1 (S-RhoBTB1) expression. Activation of RhoBTB1 expression with tamoxifen partially prevented Ang II induced HT and vascular dysfunction. However, activation of the RhoBTB1 transgene after 2-week of Ang II infusion did not reverse established Ang II HT and failed to reverse impaired vasodilation to acetylcholine and sodium nitroprusside in aorta and carotid artery. Remarkably however, arterial stiffness as measured by aortic Pulse Wave Velocity was decreased in S-RhoBTB1 compared to non-transgenic mice receiving Ang II infusion (4.6±0.4 vs 3.2±0.3 mm/ms, p<0.05, n=5-7). In conclusion, RhoBTB1 serves as CRL3 substrate adaptor and promotes PDE5 ubiquitination. Pretreatment with RhoBTB1 partially prevents Ang II HT, while restoration of VSM RhoBTB1 was not sufficient to reverse Ang II mediated HT but showed a potential in reducing arterial stiffness.
Abstract 124: NaCl Treatment Prior To Chronic Angiotensin Ii Infusion Exaggerates Vascular Inflammation And The Development of Abdominal Aortic Aneurysms By Affecting Immune Cell Response
Authors: Yakoub Mina , Temme Sebastian , Hering Lydia , Flögel Ulrich , Rump Lars C , Stegbauer Johannes
Published: September 2019

Chronic high salt (NaCl) intake is a major risk factor for cardiovascular diseases. Recent studies showed that excessive chronic NaCl intake affects immune response and thereby contributes to the pathogenesis of vascular injury. However, it remains unclear whether NaCl intake initially primes immune cell response by promoting memory T cells and sensitize the development of vascular injury in response to a subsequent stimulus. Therefore, we investigate whether 14 days of NaCl treatment (1% NaCl) followed by a 7 day washout period affects the incidence and outcome of abdominal aortic aneurysms (AAA) in apolipoprotein E deficient (ApoE-KO) mice infused chronically with angiotensin II (Ang II) (1000ng/kg/min) via osmotic minipumps for 10 days. Assessment of AAA was done by magnetic resonance imaging (MRI). To visualize vascular inflammation
in vivo
, perfluorocarbon nano-emulsions (PFC) injected intravenously before and 2, 4, 7 and 10 days after chronic Ang II infusion were detected by combining 1H/19F MRI using a
19
F RARE sequence. After 10 days of Ang II infusion, aortas with perivascular fat were dissected. Aortic inflammation and immune cells infiltration were analyzed by flow cytometery, immunohistology and realtime PCR. The survival rate of ApoE-KO mice pretreated with NaCl was significant lower and the AAA incidence rate was significant higher compared to non-NaCl treated apoE-KO mice. The amount of
19
F signal detected in areas of AAA was significantly increased in apoE-KO mice pretreated with NaCl. Histological analysis confirmed these results. At day 10, proinflammatory cytokines like TNF-alpha, iNOS and TGF-ß as well as numbers of neutrophils, monocytes as well as effector memory CD4 and CD8 T cells were significantly higher in aortas of NaCl pretreated apoE-KO mice compared to non-NaCl treated mice. In conclusion, these results suggest a significant role of NaCl in priming immune cell phenotype and thereby mediating vascular inflammation and damage in Ang II infused apoE-KO mice.
Abstract 129: The Microbiome Product Urolithin a Abrogates the Tgf-β Egfr Pai-1 Pathway by Inhibiting Egfr Activation and Expression
Authors: Melo Ana Clara , Pirro Nancy T , Tallant Ann , Gallagher Patricia E , Chappell Mark C
Published: September 2019

Introduction:
Ellagitanins are highly abundant in various foods including fruits, nuts and wines, and particularly high in commercial muscadine grape-derived supplements. The microbiome metabolizes ellagitanins to urolithins. Urolithin A (UA), the final product of the microbiome processing pathway may contribute to the cardioprotective effects of ellagitanins; however, the cellular signaling mechanisms of UA are unclear. Since the TGFβ-PAI-1 pathway contributes to fibrosis, cellular senescence and progressive kidney injury, we evaluated the effects of UA on TGFβ-induced stimulation of PAI-1 in rat renal proximal tubule cells (rPTCs - NRK52E). We hypothesize that UA may be an endogenous anti-fibrotic compound that attenuates the TGFβ-PAI-1 response.

Results:
TGFβ (5 ng/ml) treatment markedly increased PAI-1 levels 10-fold [43.9 ± 0.7 vs 3.5 ± 0.3 ng/ml; P<0.001, n=3] in the rPTCs at 24 hrs. The TGFβ receptor (TGFβR) kinase (ALK5) inhibitor SB525334 or UA abolished the increase in PAI-1 to TGFβ [SB: 1.3 ± 0.3; UA: 2.0 ± 0.4 ng/ml; P<0.001, n=3]; UA exhibits an IC50 of 3.1 μM to abrogate the TGFβ-PAI-1 response. Since the TGFβ pathway may transactivate the EGFR, treatment with the EGFR kinase inhibitors AG1478 (AG, 1 μM) and Lapatinib (LAP, 1 μM) also abrogated the PAI-1 response to TGFβ [AG: 3.3 ± 0.4; LAP: 6.2 ± 1.4 ng/ml; P<0.001, n=3]. Addition of EGF alone increased PAI-1 to a similar extent as TGFβ [46.6 ± 2.7 ng/ml; P<0.001, n=3], and treatment with UA or AG abolished the EGF-PAI-1 response [2.4 ± 0.1 and 1.3 ± 0.1 ng/ml, respectively; P<0.001, n=3]. Given the dependence on EGFR signaling for PAI-1, we determined whether UA directly attenuates EGFR stimulation. Indeed, UA treatment inhibited peak EGFR phosphorylation to EGF at 5 mins [10 μM: 67 ± 4%; 50 μM: 71 ± 5%; P<0.05, n=3], and reduced total EGFR expression at 24 hrs [10 μM: 27 ± 11%; 50 μM: 66 ± 7%; P<0.05, n=6]. UA was devoid of cytotoxic effects (LDH release).

Conclusion:
The present study is the first to establish that UA abrogates the TGFβ-EGFR-PAI-1 pathway via the inhibition of EGFR stimulation and expression. Moreover, the potency of UA to attenuate PAI-1 is comparable to its physiological levels. The microbiome product UA may convey anti-fibrotic actions within the kidney by targeting the EGFR system.
Abstract 132: COUP-TFII is a Novel Regulator of the TGF-β Pathway in Renal Fibrosis by Mediating the SMAD Signaling Cascade
Authors: Ashraf Usman , Durairajpandian Vishnuprabu , Kumarasamy Sivarajan
Published: September 2019

The Chicken ovalbumin upstream promoter factor II (COUP-TFII) acts as a transcriptional activator/repressor in a cell-type dependent manner. In our previous study, we have shown that under high salt (HS) regimen both the systolic and diastolic blood pressures (BP) and urinary protein excretions were decreased in Coup-TFII mutant rats compared to Dahl Salt-Sensitive (SS) rats. The current study extended this investigation to understand the mechanism by which a targeted disruption of
Coup-TFII
locus in SS rats leads to a renal protective phenotype. In addition a significant decrease in renal fibrosis, an improved GFR was observed in the Coup-TFII mutant rats. Since TGF-β is one of the main regulators of salt induced renal fibrosis through SMAD signaling, and therefore we tested the SMAD singling cascade. The anti-fibrotic SMAD7 level was found to be up-regulated in Coup-TFII mutant rat kidneys when compared to the SS rat kidneys. Also, we observed decrease in the levels of SMAD3 and SMAD4 and down regulation of pro-fibrotic genes such as Col1A1 and Col3A1 in Coup-TFII mutant rat kidneys. Similar observations were also found in HK2 cells deficient in COUP-TFII (HK2 -/- COUP-TFII) that the pro-fibrotic proteins such as SMAD2/3 and SMAD4 were up-regulated, however the anti-fibrotic SMAD7 levels were also up-regulated in COUP-TFII-/- HK2 cells. Furthermore, the pro-fibrotic genes such as COL3A1 was also found to be down-regulated in the HK2-/-COUP-TFII cells. Overall, our study provides evidence to believe that targeted disruption of COUP-TFII demonstrated reno-protective phenotype via regulating the SMAD signaling and thus renal fibrosis.
Abstract 134: Dopamine D
2
Receptor Modulates Wnt Expression and Control of Cell Proliferation
Authors: Konkalmatt Prasad , Kumar Megha , Asico Laureano , Freyberg Zachary , Jose Pedro A , Armando Ines
Published: September 2019

Injury to the kidney triggers a cell proliferation response that can be adaptive, leading to repair of the tubular epithelium, or maladaptive, leading to fibrosis and chronic kidney disease. The Wnt pathway is activated in response to kidney injury and contributes to the fibrotic response. Although transient activation of the pathway is needed for repair of injured tissue and increase in cell proliferation, the sustained activation may promote fibrosis. The mechanisms regulating the expression of a key Wnt ligand, Wnt3a, or the modulation of its activity are unknown. We tested the hypothesis that dopamine D
2
receptor (D2R) signaling modulates β-catenin and T-cell factor (TCF)/lymphoid enhancer factor (LEF)-mediated transcriptional activity by effects on Wnt3a expression. In mice and human renal proximal tubule cells (RPTCs) D2R downregulation (siRNA, 20 nM, 72h) or antagonism (sulpiride, 1 μM, 6h), decreased β-catenin phosphorylation and increased TCF/LEF reporter activity (50-70%, P<0.05) and Wnt3a expression. Conversely D2R agonism (quinpirole, 1 μM, 24h) increased β-catenin phosphorylation (20%, P<0.05), and decreased TCF/LEF reporter activity (35%; P<0.05) and Wnt3a expression (45%, P<0.05). Human RPTCs carrying D2R variants (SNPs) resulting in decreased D2R expression have increased expressions of Wnt3a (50%, p<0.05) and Ki-67, a cell proliferation marker, that are decreased by transient overexpression of the D2R. Furthermore, selective renal D2R silencing or renal ischemia/reperfusion in mice increases renal expression of Wnt3a and Ki-67, which are both are reversed by selective D2R overexpression in the kidney. Wnt3a and Ki-67 colocalize in the nucleus of proximal tubules cells of mice subjected to ischemia/reperfusion indicating the involvement of the Wnt/β-catenin pathway in injury-induced cell proliferation. Conversely, Wnt3a downregulation in RPTCs carrying D2R variants not only decreased Ki-67 but also decreased cell apoptosis (Tunel reaction). Our results suggest that D2R is a transcriptional modulator of canonical Wnt signal transduction with broad implications for health and development of new therapeutics.
Abstract 139: Nicotinic Acetylcholine Receptor Genes Contribute to Leptin Resistance
Authors: Li Changwei , Shen Luqi , Zhang Ruiyuan , Wang Jia-Sheng , Shen Ye , Cordero Jose , Xie Zhong-Ru , Loou Lei , Liang Lirong
Published: September 2019

Background:
The mechanisms of leptin resistance among overweight/obese individuals in not fully understood. Smokers have lower body mass index (BMI) compared to non-smokers, and quit smoking results in weight gain. Therefore, we aimed to evaluate whether smoking related genes contribute to leptin resistance.

Methods:
A total of 541 SNPs in seven genes of the nicotinic acetylcholine receptors family (
CHRNB2-B4, CHRNA3-A6
) were evaluated for interactions with leptin on BMI among 748 European American participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Significant SNPs were evaluated for replication among 3,844 participants of the Framingham Heart Study (FHS) 3
rd
generation cohort. Multivariate linear regressions were used in single SNP-based analyses controlling for age and sex. Gene-based analyses were performed using the GATES method. MESA and FHS results were combined through meta-analysis methods.

Results:
After Bonferroni correction, a total of 34 SNPs within genes
CHRNA3
,
CHRNA5
,
CHRNA6
,
CHRNB2, and CHRNB3
significantly (
P
<8.20х10
-4
, correcting for 61 linkage disequilibrium blocks) interacted with leptin on BMI, of which, 23 SNPs reached genome-wide significance (
P
<5.00х10
-8
), and 34 SNPs were successfully replicated in the FHS.
CHRNB2
rs2072661 (minor allele frequency=0.24) was most significant with a major G allele negatively interacting with leptin on BMI (MESA: β=-0.05, p=8.20х10
-4
; FHS: β=-0.05, p=1.31х10
-11
; Meta: β=-0.05, p=4.19х10
-16
), indicating that individuals with the major alleles were less resistant to leptin. Meanwhile, gene-based analysis revealed that the seven genes were all significantly interacting with leptin on BMI with meta-analysis p values ranging from 2.62х10
-13
for
CHRNB2
to 4.25х10
-5
for
CHRNA4
.

Conclusion:
Nicotine acetylcholine receptor genes modify the sensitivity of leptin on BMI.
Abstract 140: Neuronal Prorenin Receptor Deletion Attenuates Astrogliosis and Inflammation in the Arcuate Nucleus of Mice Fed With High Fat Diet
Authors: Worker Caleb J , Feng Yumei
Published: September 2019

The (pro)renin receptor (PRR) is a key component of the brain renin-angiotensin system and plays a pivotal role in the development of hypertension. However, its importance in high fat diet (HFD)-induced metabolic physiology is not well understood. We recently showed that neuron-specific PRR deletion (PRRKO) improves fasting blood glucose and glucose tolerance in mice under 16 weeks of HFD. However, the molecular mechanisms by which PRR acts remain unclear. Previous research showed that astrogliosis, characterized by enhanced glial fibrillary acid protein (GFAP) expression, is a result of HFD treatment. NF-kB signaling pathway activation leads to hypothalamic inflammation and astrogliosis. Accordingly, we hypothesized that PRR deletion in the neurons improves type II diabetes by regulating astrogliosis and inflammation in the arcuate nucleus (ARC) during HFD. To test our hypothesis, PRRKO and wildtype (WT) littermates were fed with either HFD (60% calories from fat) or normal fat chow (NFD, 10% calories from fat) with matching calories for 16 weeks. Brain tissues were immunolabeled with GFAP and NF-kB p65 and presented as relative fluorescence unit, RFU. We found that in the NFD groups, the GFAP immunolabelling was similar in the ARC (3.9 ± 1.1 vs. 2.2 ± 0.7) between WT and PRRKO mice, suggesting that PRRKO has no effect on astrocyte status in a NFD condition. Following 16 weeks of HFD, the GFAP intensity (7.6 ± 2.2, p=0.04) was significantly increased in the WT mice. PRR deletion in the neurons significantly reduced the HFD-induced astrogliosis in the ARC (4.0 ± 0.6, p=0.02) compared with the WT mice fed HFD. The NF-ĸB p65 level was elevated in the ARC of WT mice following 16 weeks of HFD compared with the NFD (13.1 ± 1.6 vs. 5.4 ± 0.6, p<0.0001). Interestingly, PRR deletion prevented the elevation of NF-ĸB p65 levels induced by HFD (6.7 ± 0.7, p<0.0001). Furthermore, astrocyte specific NF-ĸB p65 levels were higher in the WT mice fed a HFD compared to NFD (77.6 ± 1.6 vs. 14.1 ± 2.9, p<0.0001). Notably, under HFD treatment, PRRKO significantly reduced the astrocytic NF-ĸB p65 levels compared with the WT mice (33.1 ± 6.3, p<0.0001). Our data indicate that PRRKO attenuates HFD-induced type II diabetes and is associated with reduction in astrogliosis and NF-kB activation in the ARC.
Abstract 147: Copeptin and Mid-Regional Pro-ANP in Women With Suspected or Confirmed Preeclampsia: Comparison With the sFlt-1/PlGF Ratio
Authors: Neuman Rugina , Alblas van der Meer Maaike , Saleh Langeza , van den Berg Sjoerd , van den Meiracker Ton , Visser Willy , Danser Jan
Published: September 2019

Both arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) are believed to contribute to the pathogenesis of preeclampsia (PE), although current evidence is inconclusive. Here we studied AVP and ANP as biomarkers (measured as their surrogates copeptin and mid-regional pro-ANP, MR-proANP, respectively) for the prediction of PE and adverse pregnancy outcome, making use of a large prospective cohort study in 526 women with suspected or confirmed preeclampsia (age 18 - 48) originally aimed to evaluate the use of sFlt-1/PlGF ratio for the prediction of PE. Women with confirmed PE (n = 134) displayed higher copeptin (median 6 [range 1 - 61] vs. 4 [1 - 42] pM; P<0.01) and MR-proANP (52 [2 - 342] vs. 31 [2 - 298] pM; P<0.001) levels than 250 women with suspected PE. Yet, when subdividing the women according to sFlt-1/PlGF ratio (≥85 versus <85), no differences in copeptin levels were observed (5 vs. 5 pM), while MR-proANP levels remained elevated in women with a sFlt-1/PlGF ratio ≥85 (64 vs. 32 pM; P<0.0001). In accordance with this observation, copeptin correlated only marginally with sFlt-1 (r = 0.17), and not with PlGF, while MR-proANP correlated strongly with both, sFlt-1 (r= 0.30) and PlGF (r=-0.29). To discriminate maternal complications on top of traditional predictors (gestational age, parity, diastolic blood pressure and proteinuria), the sFlt-1/PlGF ratio displayed a higher C-index than copeptin and MR-proANP (0.74, 0.63 and 0.68, respectively, vs. 0.62 for the traditional predictors only), and the same was true for the discrimination of fetal/neonatal complications (C-index = 0.81, 0.76 and 0.78 vs. 0.76). Finally, multiple regression analysis revealed that both copeptin (P=0.015) and MR-proANP (P=0.024) were independent determinants of proteinuria but not blood pressure. In conclusion, both copeptin and MR-proANP levels are elevated in women with PE but have limited value to predict pregnancy complications when compared with the sFlt-1/PlGF ratio. Interestingly, copeptin (but not MR-proANP) effects appear to be largely independent from sFlt-1/PlGF, and predominantly reflect the renal phenotype in this condition.
Abstract P103: Atherosclerotic Cardiovascular Disease Risk Reduction in High Risk Populations: A Resident Driven Quality Improvement Initiative
Authors: Chang Eric Y , Abe Temidayo , Campbell Krystle , Ahmad Hadia , Anyanwoke Chisom , Odinkemere Chima , Bakinde Nicolas
Published: September 2019

Background:
Current guidelines recommend statins for patients with clinical ASCVD and more specifically, to target LDL-C levels <70mg/dL. However, recent studies suggest that overall statin usage in ASCVD patients is suboptimal (58%), with less than one-third of these individuals on a high-intensity dose. Our goal was to assess LDL-C levels amongst patients with known ASCVD within a large safety-net academic medical center, while identifying factors leading to suboptimal cholesterol control, to determine potential targeted interventions to improve patient outcomes and guideline compliance.

Methods:
We obtained data from the medical record data warehouse of a primary care outpatient medicine clinic that is predominantly staffed by internal medicine residents with attending physician guidance. Patients with a diagnosis of ASCVD who were evaluated from Jan-Dec 2016 were reviewed. Medical record abstraction was performed and bivariate analyses were conducted to identify potential factors affecting high-intensity statin prescriptions rates and resultant LDL-C levels.

Results:
Our patient population was predominantly African American (93%; 1015/1091). Statins were prescribed for 82% of these patients (897/1091), of which, only 69% (615/897) were on a high-intensity statin. However, LDL-C levels <70 mg/dL were seen in only 41% and 34% of patients on a high-intensity vs non-high-intensity statin respectively. Younger age, female sex, lack of insurance, PHQ scores >4 (indicative of mild depression or greater), and the presence of ≥4 comorbidities were all associated with a lower likelihood of being prescribed a high-intensity statin and/or having controlled LDL-C levels (p<0.05 for all variables).

Conclusion:
LDL-C control appears suboptimal among ASCVD patients within our safety-net patient population. This may reflect the inherent complexity of our patient population, which is predominantly low income, uninsured, and African American. Our future goals are to develop resident driven interventions to properly monitor LDL-C levels, escalate guideline based therapies, and manage comorbid conditions such as depression, hypertension, and diabetes, to decrease ASCVD risk and improve guideline compliance.
Abstract P108: Identify Hypertension Risk from Health Exam Results
Authors: Nguyen Thanh , Zhang Tongbin , Zhang Eric , Zhang Jianyi , Pan Chuandi , Chen Jake
Published: September 2019

Background:
In this work, we demonstrate the pratical application of machine learning in analyzing patient health exams to predict hypertension risk. Hypertension is one of the leading modifiable risk factors for cardiovascular diseases in China.

Methodologies:
The study cohort included 2,241 hypertension patients and randomly selected 2,000 normal subjects (age > 40, 49% female, 51% male) having health exam between 2010 and 2014 from the First Affiliated Hospital of Wenzhou Medical University, one of the top 20 largest hospitals in China. We analyzed hypertension risks in three steps. First, we determined which lab test results are significantly associated with hypertension using student t-test. Second, we predicted hypertension patients using deep-learning neural network. Third, we proposed a predictive risk score to estimate how long a subject would be diagnosed with hypertension following the health exam.

Results:
We identified 34 health exam lab tests which have significant associations with hypertension (Figure 1). The classification models achieved a prediction test accuracy of 99.9% and a positive predictive value of 97% with 10-fold cross-validation. The risk score clearly shows the separation of future hypertension diagnosis (p-value < 10
-6
) in Figure 1.

Discussion and Conclusions:
Our work shows that health exam lab test could effectively help data scientists to develop novel predictive models and identifyfuture hypertension risk. Since the analysis only uses lab exam data, which is affordable and frequently collected, we believe that our model and findings could be further validated and improved in other cohorts, e.g, in the United States.
Abstract P1102: Profile Characteristics of the Population Assisted in the 2018 Less Pressure Campaign of the Brazilian Hypertension Society
Authors: Guerra Grazia M , Bartholomeu Teresa , Salgado Helio C , Plavnik Frida , Tsunemi Miriam H , Angelo Luciana , D'Avila Kátia D , Berger Ana L , Brito Leandro , Evandro Cesarino Evandro , Gowdak Márcia , Bortolotto Luiz A
Published: September 2019

The Brazilian Society of Hypertension (BSH) yearly conducts the National Campaign to promote and encourage the cardiovascular health of the population.

Objective:
To characterize the profile of the population assisted in the “
Less Pressure Campaign
” in 2018.

Methods:
This is a descriptive cross-sectional study based on the campaign MMM with the general public of the São Paulo city Brazil in May. The campaign comprised multi-professional interventions made by five workshops: 1)blood pressure(BP)measurement with automatic devices; 2)exercise guidelines; 3)anthropometry, i.e., measurement of weight, height, and abdominal circumference (AC) and calculation of body mass index (BMI); 4)nutritional guidance; and 5)psychological orientation. Data analysis was in accordance with the VII BSH Guidelines, which considered values ≥140mmHg for systolic BP (SBP) and ≥90 mmHg for diastolic BP (DBP) as altered.

Results:
A total of 1184 individuals were assisted; of these, 49% (580) were men and 51%(604) were women. The mean age was 53.5±15 years, the total participants, 51% (627) declared they were normotensive, 32% (380) stated they were hypertensive and 15,3% (182) do not know if you have hypertension. The BP of 31% (380) of the individuals was altered compared with normotensive (627) as follows: SBP146.9±14mmHg vs SBP 115.8±12; DBP 90.9±10mmHg vs 76.1±8, and heart rate 78.9±14 vs of 79.2±12, respectively between hypertensive, normotensive individuals. The anthropometric data of the participants with altered BP compared with normotensive population were the following: weight was statistically significant (p=0,0407) 77±15kg vs 71.9±18Kg; BMI was statistically significant (p=0,0007) 27.5±14Kg/m2 vs 21.9±22Kg/m2; and AC was statistically significant (p=0,0000) 98.5±11 vs 96.4±11cm respectively between hypertensive and normotensive individuals. When analyzing the association between sex and hypertension, it was identified that 48.9% (186) hypertensive were female and 51% (194) were male, when the association was assessed no statistical difference was found (p=0.0658) between sex and hypertension.

Conclusions:
The study points to the need for investment in educational and awareness actions to promote better control of the hypertensive population
Abstract P1109: Cholesterol Regulation of Hydrogen Sulfide-Mediated Vasodilation
Authors: Mendiola Perenkita J , Gonzalez Bosc Laura V , Kanagy Nancy L
Published: September 2019

Hydrogen sulfide (H
2
S) is produced within the vascular wall by cystathionine γ-lyase (CSE). CSE is expressed throughout the vascular tree however, the sensitivity to H
2
S-induced dilation in small resistance size arteries (<100 μm) is greater than the dilation sensitivity in large arteries (>300 μm). Although H
2
S can induce vasodilation in different size arteries, it is not clear how H
2
S signaling mechanisms differ in large and small arteries, garnering H
2
S-induced dilation prominent and important in small resistance arteries. We previously demonstrated that within endothelial cells, H
2
S-mediated vasodilation involves activation of transient receptor potential cation channel subfamily V member 4 (TRPV4)-dependent Ca
2+
influx and large conductance Ca
2+
-activated potassium (BK) channel. Based on previous reports that membrane cholesterol negatively regulates TRPV4 mobility and BK activity, we hypothesized that H
2
S-mediated vasodilation is diminished by membrane cholesterol and that lower sensitivity in large arteries might be due to higher levels of membrane cholesterol in endothelial cells. Isolated pressurized mesenteric arteries (300-380 μm) were treated luminally with vehicle (HEPES) or the cholesterol-depleting agent, methyl β cyclodextran (MBCD, 100 μM) and exposed to H
2
S donor, NaHS (10 μM). Analysis of H
2
S-induced dilation (expressed as % Ca
2+
free diameter) showed that MBCD treatment significantly enhanced H
2
S-mediated vasodilation (vehicle: 1.2% ± 1.2, MBCD: 8.9% ± 2.3, p = 0.012, n = 5 animals/group). Additionally, mesenteric arteries of different orders were luminally loaded with the fluorescent cholesterol-binding agent, filipin III (20 μg/ml, ex/em: 405/461 nm) the endothelial glycocalyx marker DyLight 594-tomato lectin (20 μg/ml, ex/em: 561/613 nm) and the nuclei stain SYTOX green (ex/em: 488/518 nm). Analysis of endothelial membrane cholesterol content (filipin III /tomato lectin fluorescence) was significantly greater in larger arteries (2
nd
order: 1.019 ± 0.158, 5
th
order: 0.344 ± 0.179, p = 0.0054, n = 3-5 animals/group). These studies suggest that higher membrane cholesterol decreases H
2
S-mediated vasodilation.
Abstract P111: Renal Perfusion Pressure Determines Renal Leukocyte Infiltration During Angiotensin II-Induced Hypertension in Sprague Dawley Rats
Authors: Shimada Satoshi , Abais-Battad Justine M , Alsheikh Ammar J , Stumpf Megan , Kurth Theresa , Evans Louise , Mattson David L , Cowley Allen W
Published: September 2019

A large body of work demonstrates an important role of renal infiltrating leukocytes in the development of hypertension and end-organ damage. We recently reported that the renal leukocyte infiltration during high salt-induced hypertension in Dahl Salt Sensitive (SS) rats was dependent on the elevated renal perfusion pressure (RPP). Here we performed studies to determine if the observed effects were limited to the Dahl SS rat and to separate out the effect of the high salt diet. We report here that renal leukocyte infiltration during Angiotensin II-induced (AngII) hypertension in rats is mediated by an increased RPP. Male Sprague-Dawley rats (n = 6) were maintained on a 0.4% NaCl diet throughout the study. At 9 weeks of age, rats were instrumented with carotid and femoral arterial catheters for measuring blood pressure (BP), a femoral venous catheter for AngII infusion, and a balloon occluder cuff was placed around the abdominal aorta between the renal arteries. The carotid and the femoral mean arterial pressures were used as surrogates for the RPP of the right and left kidneys respectively. After 7 days of recovery, baseline BP was measured for 3 days, then the rats were infused with AngII (50 ng/kg/min) for 7 days to induce hypertension. A computer-driven servo-control system was used to inflate the aortic cuff to maintain left RPP at baseline levels while right RPP was uncontrolled. Following 7 days of Ang II infusion, kidneys were removed to assess leukocyte infiltration by flow cytometry, and animals were euthanized. Baseline RPP was similar between right and left kidneys (115.6±3.9 vs 110.5±4.3 mmHg respectively). However, following 7 days of AngII infusion, the right RPP was significantly higher than left RPP (164.7±9.9 vs 112.5 ± 4.2 mmHg; respectively p<0.001). Significantly greater numbers of infiltrated leukocytes were found in the right compared to the left kidney (1.00±0.24 vs 0.53±0.10 X10
7
CD45+cells/kidney p=0.04) and assessment of the subsets found greater numbers of T cells (CD3+), B cells (CD45R+) and monocytes/macrophages (CD11b/c+) in the right kidney compared to the servo-controlled left kidney. The findings from these studies strongly support a critical role for RPP in renal leukocyte infiltration during AngII hypertension in rats fed low salt.
Abstract P1114: Impairment of Nitric Oxide Induces Volume Expansion in Normotensive Salt-Sensitivities by Activating NCC
Authors: Wang Conghui , Mori Fumiko , Kang Lei , Ayuzawa Nobuhiro , Ogura Sayoko , Chen Xiangmei , Fujita Toshiro , Shimosawa Tatsuo , Koid Suang S
Published: September 2019

Background:
It is still controversial if salt-sensitivity in terms of regulation of circulating volume in normotensive. In the present study, we investigated the role of NO on salt-sensitivity by measuring salt-induced increases in circulating volume and its underlining mechanisms.

Method:
We measured circulating volume, change in blood pressure and renal sodium-chloride cotransporter (NCC) activation, both in vivo in SD rats, wild-type mice and NCC deficient mice, and in vitro in mDCT cells.

Result:
The blood volume was comparable between the groups during NS diet period, and increased a day after HS loading. The blood volume returned to the level of NS period in HS group, in contrast, continuously increased in L-NAME + HS group (Fig A). Corresponding to the increases in blood volume, HS+L-NAME group increased blood pressure (Fig B) (MBP: HS: 105.7 ± 4.1 vs. HSL: 111.5 ± 3.5 mmHg). This blood pressure response to high salt diet was reproduced in C57BL/6J mice after 4 weeks treatment (HS: 108.7 ± 3.7 vs. HSL: 130.5 ± 2.9 mmHg). There is no kidney morphological changes. In vivo experiments showed that HCTZ but no amiloride induced larger natriuretic effect in L-NAME+HS group, which suggest NCC rather than ENaC is responsible. The phosphorylated NCC is reduced after HS but it sustained in L-NAME+HS group. Moreover, the results from NCC-deficient mice support that NCC is indispensable for L-NAME induced salt sensitivity. In addition, the membrane NCC expression was decreased by NO in a time and dose depended manner in mDCT cells.

Conclusion:
Low dose L-NAME induces volume expansion leading to salt-sensitivity by inappropriately and directly activate NCC in both vivo and vitro.
Abstract P1117: Dissimilarities Between and Carotid and Forearm Pressure-Decay and Windkessel Parameters: Implications for Circulatory Models
Authors: Izzo Joseph L , Anwar Muhammad Absar , Elsayed Sherif , Osmond Peter , Gavish Benjamin
Published: September 2019

We studied whether: 1) the carotid and forearm diastolic pressure-decay time constants (tau) are similar and 2) the associated Windkessel (WK)-derived compliance and stiffness values are also similar and are related to arterial stiffness. Ambulatory normotensive and hypertensive subjects were studied after 30 minutes of supine rest with radial and carotid arterial tonometry (Sphygmocor), standard oscillometric cuff BP, and central (heart-femoral, hf) and peripheral (femoral-ankle, fa) pulse wave velocity (PWV, Colin VP1000). Brachial and carotid Doppler flow studies were performed in a subset. Tonograms were photo-digitized and the pressure in late diastole was modeled as an exponential decay to an asymptote A with time constant tau and start-decay time t0. [Resistance = mean pressure/flow; WK compliance = tau/resistance and WK stiffness = 1/WK compliance.] Tonometry and PWV data were available in 98 individuals; carotid and forearm blood flow in 22: (mean[SD]) age 50[20] years, weight 81[17] kg, BP 134/77[17/12] mmHg, resting HR 66[12], 38% female. Data are presented in the Table; hfPWV and faPWV were well correlated (p<0.001) but neither was correlated with carotid or forearm tau or the corresponding regional WK stiffness. We conclude that diastolic pressure decay (tau) and WK stiffness (or compliance) are not systemic indicators but rather unique regional characteristics not related to central or peripheral large artery stiffness. These findings suggest that single-WK models do not adequately represent the arterial circulation.
Abstract P1119: Serum Gdf-15 is a Determinant Factor of Renal Vascular Resistance in Patients With Essential Hypertension
Authors: Shichijo Satoru , Okura Takafumi , Nagao Tomoaki , Kondo Fumikazu , Makita Ayu , Yamaguchi Osamu , Miyoshi Kenichi
Published: September 2019

Introduction and Aims:
Growth differentiation factor-15 (GDF-15), a member of TGF-beta family, has been implicated in several pathological conditions, which include inflammation, cancer, cardiovascular, pulmonary and renal diseases. Recently it is reported that serum GDF-15 may be a marker for chronic kidney disease (CKD) and CKD progression. In present study, we evaluated whether serum GDF-15 is associated with renal vascular resistance evaluated by resistive index (RI) measured in Ultrasound, which is the marker of renal injury.

Methods:
Eighty patients with essential hypertension were enrolled in this study. They were evaluated on serum GDF-15 and renal RI as well as for conventional atherosclerotic risk factors.

Results:
Mean age of all patients was 66 ± 12 years (35 males and 45 females). Mean eGFR and renal RI was 68.9 ± 23.0ml / min / 1.73m2 and 0.71 ± 0.07 respectively. Mean serum GDF-15 was 1492 ± 1319 pg/ml. RI correlated with GDF-15 (r=0.47, P<0.001), age (r=0.40, p<0.001), eGFR (r=-0.34, p=0.002) and diastolic BP (r=-0.56, p<0.001) in simple regression analysis. Multiple regression analysis showed GDF-15 (beta=0.31, P=0.005) and systolic BP (beta=0.35, P<0.001) and diastolic BP (beta=-0.74, P<0.001) were the independent determinants of renal RI.

Conclusions:
GDF-15 is associated with renal vascular resistance and may become a nephropathic marker in patients with hypertension.
Abstract P1123: The Pharmacological Basis for Vasodilator Effect of
Sisymbrium Irio
Linn. Validates it's Folkloric Use in Hypertension
Authors: Ahmed Muhammad Masood , Hussain Musaddique , Farooq Umer , Raza Shahid Masood , Andleeb Shumaila , Majeed Abdul , Shah Syed Nisar Hussain
Published: September 2019

Traditionally seeds of
Sisymbrium irio
Linn has been used in different regions of Pakistan for the treatment of gastrointestinal, airways and vascular system ailments. To insight the pharmacological basis
in vitro
study was conducted in order to validate its folkloric uses in hypertension. 70% aqueous-methanolic extract of seeds from
Sisymbrium irio
(Si.MEs) was tested on isolated rabbit aorta, jejunum and trachea strip hanged in tissue bath having physiological solutions aerated with carbogen and their responses were measured and recorded via Power Lab. The Si.MEs exhibited the transient spasmogenic effect (0.01-1.0 mg/mL) on spontaneous jejunum contractions, followed by the spasmolytic effect. The addition of atropine resulted in blocking in spasmogenic effect while the spasmolytic effect was originated, suggesting the presence of an antimuscarinic effect. Likewise verapamil, Si.MEs (0.03-5 mg/mL) repressed the high concentration K + (80 mM)-induced contraction and also drifted the Ca
2+
concentration-response curves toward right (0.3-3.0 mg/mL), possibly signifying the Ca
2+
channel blockade. Furthermore, Si.MEs exhibited nonspecific relaxant effect on carbachol (1 μM)- and high concentration K
+
(80 mM)-induced tracheal contractions in a way comparable to dicyclomine, suggesting the coexistence of Ca
2+
antagonistic and/or antimuscarinic properties. Additionally, Si.MEs also relaxed the phenylephrine(1 μM)- and high concentration K
+
(80 mM)-induced aortic contraction (0.01-3 mg/mL), suggesting blockade of Ca
2+
channel. Moreover, oral administration of Si.MEs, as high as 6 g per kg, did not produce lethality among the treated groups of mice. Aqueous-methanolic extract of seeds from
S. irio
(Si.MEs) exhibited the bronchodilator and gut modulator (spasmogenic and spasmolytic) activities, probably through dual blockade of muscarinic receptors and Ca
2+
channels, whereas, vasodilator effect may be due to Ca
2+
channels blockade validates its use in hypertension.
Abstract P1125: Serum Metabolite 1-Methylhistidine, a Marker of Red Meat and Poultry Consumption, Independently Associates With Increases in Systolic and Diastolic Blood Pressure in Middle-Aged Adults
Authors: Razavi Alexander C , Fernandez Camilo , Bazzano Lydia A , He Jiang , Krousel-Wood Marie A , Nierenberg Jovia , Shi Mengyao , Li Changwei , Mi Xuenan , Li Shengxu , Kinchen Jason , Whelton Seamus P , Kelly Tanika N
Published: September 2019

Introduction:
Red meat consumption associates with heightened cardiometabolic risk. Urinary metabolite 1-methylhistidine (1-MTH) has been shown to correlate with red meat, poultry, and to a lesser extent fish consumption, serving as a quantitative biological marker of intake. We aimed to confirm this relationship and assess the novel role of serum 1-MTH in blood pressure (BP) among a biracial (African American-White) community-based cohort of middle-aged adults.

Methods:
This study consisted of 655 participants of the Bogalusa Heart Study (25.0% African-American, 60.8% female, aged 33.6-58.1 years) not taking antihypertensive medication. From 2013-2018, systolic and diastolic BP were recorded using an oscillometric method. Fasting serum 1-MTH was quantified using liquid chromatography-tandem mass spectroscopy using a median standardized scale. Red meat, poultry, and fish intake were quantified by food-frequency questionnaires. Analyses of animal food consumption with 1-MTH were performed using bivariate linear regression. Multivariable linear regression assessed the independent association of 1-MTH with systolic and diastolic BP in combined and race-stratified analyses, adjusting for a wide variety of traditional demographic, dietary and cardiometabolic risk factors.

Results:
Red meat (B=0.004; p=0.001) and poultry (B=0.005; p=0.05), but not fish intake, were significantly associated with serum 1-MTH. Serum 1-MTH had a significant positive association with both systolic (B=10.45, p=0.04) and diastolic BP (B=6.44, p=0.04) consistently in African-Americans, but not Whites. Among a subgroup of 86 individuals who were normotensive at baseline with repeat outcome measures (median follow-up time=2.98 years), we observed a 5.30 and 5.13 mmHg per-year increase in systolic (p=0.03) and diastolic BP (p=0.002), respectively, for every one unit increase in serum 1-MTH.

Conclusion:
Red meat and poultry intake correlate with serum 1-MTH. Notably, serum 1-MTH independently associates with considerable increases in systolic and diastolic BP, more consistently in African-Americans compared to Whites. These findings may aid in strengthening cardiometabolic prevention efforts via dietary recommendations, in a race-specific fashion.
Abstract P1126: Neutrophil Extracellular Traps: New Players in Hypertension
Authors: Vijay-Kumar Matam , Saha Piu , Yeoh Beng San , Golonka Rachel , McCarthy Cameron , Spegele Adam , Abokor Ahmed , Chakraborty Saroj , Mell Blair , Koch Lauren , Joe Bina
Published: September 2019

Aberrant immune responses are linked to hypertension; yet, neutrophils remain relatively understudied. Both neutrophilia and elevated neutrophil-to-lymphocyte (N/L) ratio are used as clinical biomarkers of hypertension. Likewise, neutrophilia is reported in spontaneously hypertensive rats. Whether these features are associated with an increase in neutrophil extracellular traps (NETs) generation is unknown. We hypothesized that neutrophilia and NETs directly correlate with hypertension whereby lowering neutrophilia and NETs are therapeutically beneficial to lower blood pressure (BP). Herein, we used various, genetic rat models divergent in BP to study the neutrophil-hypertension axis. These include the Dahl Salt-Sensitive (S) and Resistant (R) rats, and the low (LCR) and high (HCR) exercise capacity runner rats. LCR (2.1±0.3 10
9
/l) and S rats (1.2±0.5 10
9
/l) exhibited neutrophilia compared to HCR (0.98±0.5 10
9
/l) and R rats (1.04±0.5 10
9
/l), p<0.05, respectively. To determine whether neutrophil function was also augmented, peripheral neutrophils were stimulated with either PMA or LPS to induce ROS and NETs generation, respectively. LCR and S rats generated ~2-3 folds more ROS and NETs compared to their HCR and R counterparts. Intriguingly, LCR (11.4±1.0 U/ml) displayed reduced DNase I activity than HCR (17.8±0.8 U/ml), p<0.05, which indicated an inadequate clearance of NETs. Systemic and renal lipocalin-2 were 2-3 folds higher in the S rats compared to R rats, suggesting low-grade inflammation associated with NETs overabundance. Introducing a high-salt diet to S and R rats further potentiated neutrophilia, ROS and NETs, the extent of elevation being higher in S rats. Opposingly, oral administration of β-hydroxybutyrate (βOHB; a hypotensive ketone body) to S and R rats reduced neutrophilia, NETs and ROS. Similarly, subjecting LCR to exercise and fasting, both of which lower BP and increase βOHB, substantially attenuated neutrophilia, NETs and ROS. Collectively, our results demonstrate that NETs are an important feature directly linked to elevated BP in a strain-independent manner. Thus, blunting neutrophil responses through dietary intervention or exercise could serve as a novel therapeutic strategy against hypertension.
Abstract P1127: Reverse Feeding Abolishes Circadian Blood Pressure Rhythms in Bmal1-Knockout Rats
Authors: Rhoads Megan K , Jin Chunhua , Pollock David M
Published: September 2019

Blood pressure follows a strong circadian rhythm regulated by the molecular clock, which can be entrained by light, feeding, and other cues. Using a whole body knockout of a central clock gene, Bmal1 (Bmal1KO), we tested the hypothesis that food availability would entrain circadian blood pressure rhythms with a functional molecular clock. Male and female rats were implanted with a telemetry transmitter to measure 24-hour mean arterial pressure (MAP). Following recovery, rats were placed in metabolic cages to measure food and water intake. Rats were allowed ad lib access to food for three days and then food was restricted to the inactive period (lights on, 7 am to 7 pm) for five days. Under ad lib feeding conditions, male littermate control rats (n=8) had a MAP of 113.3±2.6 mmHg during the inactive period and a significantly higher MAP during the active period (120.6±3.1 mmHg, repeated measures ANOVA with Sidak’s post hoc, p<0.0001). Similarly, Bmal1KO rats (n=12) had a significantly higher MAP during the active period (114.5±1.8 mmHg) versus the inactive period (108.9±2.0 mmHg, p<0.0001). Under reverse feeding conditions, control rats had an average MAP of 118.3±2.5 mmHg during the inactive period and a significantly higher MAP to 121.7±2.8 mmHg during the active period (p<0.0001). Bmal1KO rats had similar MAPs during the inactive and active periods (113.1±1.7 vs. 113.3±1.8 mmHg, respectively, p=0.99). During ad lib feeding, female control rats (n=7) had a significant diurnal pattern with an average MAP of 110.6±1.4 mmHg in the inactive period and 118.9±1.9 mmHg during the active period (p<0.0001). Female Bmal1KO rats (n=3) had an average MAP of 104.7±0.4 mmHg in the inactive period and a significantly higher MAP of 110.5±0.3 mmHg during the active period (p<0.001). Under reverse feeding conditions, female control animals maintained a significant diurnal MAP from inactive to active periods (110.6±1.5 vs. 115.3±1.9 mmHg, respectively, p<0.0001), but female Bmal1KO animals had no significant difference in inactive and active period MAP (105.0±0.3 vs. 106.8±0.4 mmHg, respectively, p<0.0001). Together, these data suggest that food availability contributes to the circadian blood pressure rhythms in male and female Bmal1 knockout rats.