bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2047: Human Renal Proximal Tubule Cells Cultured Under High Salt Conditions Increase Angiotensin Type 2 Receptor Abundance In Secreted Exosomes
Authors: Laterza Nicholas C , Gildea John J , Xu Peng , Schiermeyer Katherine A , Felder Robin A
Published: September 2019

The dopamine type 1 (D
1
R) and angiotensin type 2 (AT
2
R) are both natriuretic receptors that regulate renal sodium homeostasis. Aberrant D
1
R and AT
2
R mechanisms are implicated in hypertension, salt-sensitive hypertension, and in normotensive salt sensitives. Increased AT
2
R recruitment to the plasma membrane has been shown to occur when the D
1
R is stimulated by dopamine and increases with increased extracellular and intracellular sodium. RPTCs secrete exosomes which are plasma membrane vesicles between 50 and 90 nm in diameter and which encapsulate proteins and microRNA from the cell. We hypothesized that exosomal AT
2
R may reflect plasma membrane abundance of the RPTCs responding to the exposure to increased sodium. This study examined the abundance of the AT
2
R found on the surface of these exosomes in response to changing salt concentrations. Immortalized hRPTC were treated in serum free media cultured overnight with either an additional 50 mM sodium chloride or choline chloride as an osmotic equivalent, and exosomes were purified and concentrated from cell culture supernatant. The exosomes were then captured with magnetic lectin affinity beads and immunostained with fluorescent AT
2
R that increased in high salt conditions compared to vehicle control treated cells (VEH 71,884±7099 RFU, n=17, 190 mM Sodium, 94,180±5487 RFU, n=16, p= 0.018, t-test). The increase levels of AT
2
R are appropriate for their natriuretic activity. Future work will examine this response as it relates to salt sensitivity and inverse salt sensitivity of blood pressure as we previously reported using miRNA.
Abstract P2050: The Pcornet Blood Pressure Control Laboratory
Authors: Pletcher Mark J , Fontil Valy , Carton Thomas , Shaw Kathryn , Smith Myra , Todd Jonathan , Chamberlain Alanna M , Obrien Emily , Faulkner Madelaine , Maeztu Carlos , Wozniak Gregory , Rakotz Michael , Shay Christine , Cooper DeHoff Rhonda M
Published: September 2019

Background:
New technology and healthcare delivery approaches may help improve blood pressure (BP) control. Randomized controlled trials (RCTs) can demonstrate effectiveness of these emerging approaches, both overall and especially within underserved populations, but RCTs are expensive. Our objective is to establish a national platform to support BP control surveillance and efficient RCTs.

Methods:
The PCORnet BP Control Laboratory, designed and launched in partnership with the American Heart Association (AHA) and the American Medical Association (AMA), leverages electronic health record (EHR) systems throughout the US, the National Patient-Centered Outcomes Research Network (PCORnet), and the NIH-funded Eureka Research Platform, which enables direct-to-participant research including collection of patient-reported outcomes and mHealth data from wearable devices and smartphones. We will use these resources to 1) Conduct national surveillance through quarterly EHR data queries to calculate and track institution- and clinic-level BP control metrics across 23 PCORnet institutions, overall and within key subgroups, and support participation in the AHA/AMA’s Target:BP recognition program (BP Track); 2) Compare effectiveness of a Full Support versus Self-Guided version of the AMA’s Measure Accurately, Act Rapidly, and Partner with Patients (MAP) program at improving BP control in a cluster randomized trial of 24 safety net clinics (BP MAP); and 3) Compare effectiveness of Smartphone-linked versus standard home BP monitoring at reducing systolic BP in an individual-level, direct-to-participant RCT of 2000 patients with uncontrolled BP (BP Home).

Results:
Preliminary BP Track queries demonstrate an overall BP control rate of 56%, lower control in Black patients (51%), substantial heterogeneity in clinic-level metrics (e.g., 33% vs. 64% BP control), and low rates of medication intensification (9% prescribed a new medication class when BP was high). BP Track will launch PCORnet-wide queries in June; BP MAP in May; and BP Home in August 2019.

Conclusions:
Feasibility testing is underway to determine if the PCORnet BP Control Laboratory will be useful for investigators interested in conducting efficient RCTs of BP control interventions.
Abstract P2056: Effect of Ambulatory BP Load on Target Organ Damage in Youth
Authors: Urbina Elaine M , Ferguson Michael , Lande Marc , Meyers Kevin , Samuels Joshua , Flynn Joseph T
Published: September 2019

Ambulatory BP (ABP) is increasingly used for diagnosis of hypertension (HTN). Pediatric but not adult guidelines consider BP load (%readings above 95th%) in risk-stratification of the ABP phenotype. We evaluated load as a predictor of target organ damage (TOD) in youth. We measured casual BP, ABPM (Spacelabs Inc., Snoqualmie, WA), body mass index (BMI), LV mass index (LVMI), systolic and diastolic function (E’/e’ ratio) and pulse wave velocity (PWV) in 367 adolescents (15.6 +/- 1.7 years, 63% white, 58% male). Subjects were stratified by load (<25% Low=215, 25-<50% Mid=62, >=50% High=47) by sex- and height-specific pediatric cut-points. ANOVA was used to evaluate differences in CV risk factors and TOD across groups. General linear models were used to determine if load was an independent predictor of TOD after adjustments. There were no differences in age, demographics or BMI by group. There was a graded increase in most clinic and ambulatory BP means and loads across groups (all p ≤0.05). There was only a trend for higher LVMI (p=0.06) and reduced strain (p=0.05) in low vs high groups. Diastolic function (E/e’) was lower in high vs low and mid groups and there was a graded increase in arterial stiffness (PWV) across groups. Daytime SBP load was an independent determinant of all forms of TOD after adjusting for age and sex but lost significance for LVMI after adjusting for BMI%. Load percent and load group remained significant determinants of PWV & E/e’ after adjusting for age, sex, BMI% and mean daytime ambulatory SBP (all p ≤ 0.0001). We conclude that daytime SBP load adds to prediction of diastolic dysfunction and arterial stiffness but not LVMI or systolic function.
Abstract P2058: Using Mobile Health Technology to Increase Knowledge About Hypertensive Patients Requests and Health Behaviors
Authors: Carlsson Martin H , Darwiche Gassan
Published: September 2019

Background:
The use of virtual health intervention and the use of home blood pressure monitoring (HBPM) has been shown to improve empowerment, compliance and blood pressure control.

Aims:
The aim of the present study was to use a smartphone application for hypertension treatment to investigate the patients' perception of how hypertension affected their lives.

Methods:
The target group was patients with primary hypertension without diabetes or major cardiovascular complications living in Stockholm, Sweden (males/females 132/153, mean age 58 years). When a patient had been included, a smartphone application (Accumbo, Sweden) was downloaded. HBPM were measured with a Bluetooth connected oscillometric BP monitor. A questionnaire was filled in electronically.

Results:
Mean blood pressure was 135/87 mmHg. Based on the questionnaire 71 % (190 out of 267) of the patients had never received information from their doctor regarding the aetiology of their disease. Only 37 % (103 out of 277) had received individual health advice. When asked “How is your health in general”? 54% (154 out of 285) responded good or very good. On the other hand 47% (128 out of 281) of patients answered that having an elevated blood pressure affected their daily activities. Most patients, 79 % (222 out of 282) wanted to lose weight. Forty percent (110 out of 278) stated that they received little or very little daily exercise. Sixty eight % (190 out of 279) wanted to increase their daily physical activity if possible. Only 8% (26 out of 279) did not want to increase their daily exercise. Fifty six percent (156 out of 276) patients used a lifestyle or health app in their smartphone and 43 % (121 out of 280) patients had taken dietary supplements, or vitamins the month before the study.

Conclusion:
Few hypertensive patients had received individual lifestyle advice although the majority of patients had a desire for weight loss and increased physical activity. Most patients were aware of the complications of hypertension and the use of alternative therapies such as dietary supplements and health and lifestyle apps were very common. Traditional health care should increase the use of digital questionnaires in order to obtain increased information about patient's lifestyle factors for better targeted treatment.
Abstract P2063: Isolated Noradrenergic Failure Due Tocongenital Cyb561 Deficiency
Authors: Shibao Cyndya A , Garland Emily M , Black Bonnie K , Mathias Christopher J , Grant Maria B , Root Allen W , Robertson David , Biaggioni Italo
Published: September 2019

CYB561 generates ascorbic acid, a cofactor for the function of dopamine-beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine. We report a novel genetic defect in the
CYB561
gene and provide the clinical characteristics of CYB561 deficiency. We evaluated 4 patients referred for life-long disabling orthostatic hypotension and performed whole genome sequencing of the CYB561 gene. Patients had disabling orthostatic hypotension (OH) since infancy and impaired blood pressure response to the Valsalva maneuver (VM) with exaggerated phase 2 hypotension and absence of phase 2 late recovery and phase 4 blood pressure overshoot consistent with sympathetic failure. Heart rate ratio to sinus arrhythmia and the VM, however, were normal. Plasma norepinephrine and metabolites were undetectable, and plasma dopamine and metabolites were normal. Droxidopa restored norepinephrine and improved orthostatic hypotension. Patients 1 and 2 were sisters and were homozygous for a nonsense mutation in Exon 2, c.131G>A, p.Trp44 (Circ Res 2018). Their brother (patient 3) died at age 16 and his DNA was not available. Patient 4 was compound heterozygous; one allele had a mutation in Exon 2, c157C>T, p.His.53Tyr, and the other had an Exon 2 deletion. In conclusion, CYB561 deficiency is characterized by isolated sympathetic noradrenergic failure with disabling orthostatic hypotension since infancy, but with normal sympathetic cholinergic (sweating) and parasympathetic (heart rate regulation) functions. The genetic defect differed between patients; we report a novel case of CYB561 deficiency due to compound heterozygosity, with a gene deletion in one allele, and a missense mutation in the other. These patients highlight the critical role of CYB561 in sympathetic function and cardiovascular regulation.
Abstract P2065: Effect of Denture-Related Stomatitis on Blood Pressure and Heart Rate Variability
Authors: Ribeiro Adriana B , Araujo Camila B , Bueno Franklin L , Silva Luiz E , Fortes Caroline V , Salgado Helio C , Fazan Rubens , Silva-Lovato Claudia H
Published: September 2019

Denture-related stomatitis (DRS) has recently been associated with harmful cardiovascular effects, including arterial hypertension. This study evaluated salivary parameters, blood pressure (BP) and heart rate variability (HRV), before and after the DRS treatment in edentulous patients (n=14). Collection of unstimulated and stimulated saliva, as well as blood pressure BP measurements and electrocardiogram recordings, were performed before and after ten days of DRS treatment. The salivary flow (mL/min) was found similar at both times while the pH was smaller (more neutral) after the treatment (7.3±2.2 vs. 7.1±0.24). The systolic BP (mmHg) showed a trend, but not a significant reduction after the DRS treatment (158±25.68 vs. 148±16,72, p=0,062) while diastolic BP was found similar in both times (86±13.93 and 84±9.38). Overall, the HRV measured by the standard deviation of RR intervals was not affected by DRS treatment (24±4 vs. 18±2 ms); but the differences of successive RR intervals (an index of parasympathetic cardiac modulation) increased after the treatment (26±4 vs. 19±2 ms). Moreover, another index of vagal modulation of the heart, i.e., the power of RR interval spectra at high-frequency, was also markedly higher after the DRS treatment (236±63 vs. 135±32 ms
2
). Overall, these findings strongly suggest that the DRS is associated with an autonomic imbalance, particularly with sympathetic overactivity. Therefore, the DRS may be significantly harmful, increasing cardiovascular risk and the incidence of several diseases, for instance, arterial hypertension.
Abstract P2068: Whole Exome Sequencing And Monogenic Hypertension In A Multiethnic Cohort Of 28,000 Individuals
Authors: Paranjpe Ishan , Johnson Kipp , Coca Steven G , Chan Lili , He Cijiang , Murphy Barbara , Narula Jagat , Do Ron , Nadkarni Girish N
Published: September 2019

Hypertension (HTN) is a major cause of morbidity and mortality and a subset may be caused by monogenic mutations. We identified the prevalence of these mutations in a multiethnic cohort and determined their association with blood pressure, appropriate diagnosis, and adverse cardiovascular outcomes.

In 27,972 individuals from the Bio
Me
Biobank (8304 European, 6993 African, 9985 Hispanic, and 2690 Other ancestry), we identified ClinVar mutations pathogenic for secondary hypertension using exome sequencing.

3125 individuals (11.2%) had pathogenic mutations with a majority in genes associated with catecholamine excess (
SDHD
,
SDHB
,
TMEM127
,
RET
; n=1976) and sodium handling/hyperaldosteronism (
SCNN1G/ CYP11B1
; n=384). (Fig 1A,B) In a linear model adjusted for sex, age, BMI, and 10 genetic principal components (PCs), individuals with mutations had elevated mean arterial pressure (β=0.7±0.6 mmHg; p=0.03) and increased odds of CAD (adjusted OR=1.12, 95% CI 1.0 to 1.3, p=0.04). Individuals with mutations in sodium handling/hyperaldosteronism genes had increased odds of CHF (adjusted OR = 1.44, 95% CI 1.04 to 1.97; p=0.02) adjusted for age, sex, 10 genetic PCs, and systolic blood pressure. The majority of individuals with mutations were diagnosed with essential HTN (54.2%) and only 7.8% had appropriate diagnoses of secondary HTN or received appropriate biochemical evaluation. (Figure 1C)

Individuals with pathogenic mutations had higher blood pressures, elevated risk for CAD/CHF and the majority were not appropriately evaluated or diagnosed. These results suggest exome sequencing may have utility in hypertension diagnosis and management.
Abstract P2069: The Study Of Influencing Factors For Microalbuminuria With Essential Hypertension In Tibet
Authors: ZHAO Liming
Published: September 2019

Obiective:
To investigate the influencing factors for microalbuminuria in Tibetan hypertensive patients.

Methods:
The study was a cross-sectional study, which was performed at the hospital of Chengdu office of people’s government of tibet autonomous region (Chengdu, China). From 2017.3 to 2018.3, 369 consecutive essential hypertension patients without treatment were enrolled in the study, and these patients were from Tibet at an altitude of 2500-5000 m. Medical professionals did a survey according to the study protocol, including standardized questionnaire, physical examination and laboratory tests. Urine samples were collected for microalbumin detection in the morning, and microalbuminuria was defined as the albumin to creatinine ratio (ACR) ≥ 300 mg/g.

Results:
Compared with the negative microalbumin group (n = 303), the positive group (n = 66) had higher systolic blood pressure (SBP) (142.2 ± 18.4 vs. 139.0 ± 17.0 mm Hg, p = 0.001), diastolic blood pressure (DBP) (89.6 ± 15.9 vs. 82.5 ± 12.5 mm Hg, p = 0.001), serum uric acid (402.7 ± 108.9 vs. 364.9 ± 102.8 μmol/l, p = 0.009), total cholesterol (TC) (4.9 ± 1.1 vs. 4.4 ± 1.1 mmol/l, p = 0.001), low density lipoprotein cholesterin (LDL-C) (2.8±0.9 vs. 2.6±1.0 mmol/l, p = 0.038), erythrocyte (5.1±1.0 x10
9
vs. 4.7± 0.7 x10
9
/l, p = 0.001), hemoglobin (158.1 ± 30.9 vs.141.1 ± 20.6 g/l, p = 0.001) and homocysteine (19.1 ± 17.3 vs. 15.2 ± 8.6 μmol/L, p = 0.001) . Based on the upper reference limit of variables, these variables were divided into the low and high value groups. With the low value group as reference, univariate analysis showed that , the high value groups of hemoglobin,SBP, homocysteine and TC were positively related with microalbuminuria. After adjustmentfor confounders, multivariate analysis suggested that the high value groups of hemoglobin,SBP, homocysteine and TC,were still positively related with microalbuminuria, and the ORs were 4.08 (95% CI:1.79-9.28, p = 0.001) for hemoglobin,2.35 (95% CI:1.33-4.17, p = 0.003) for SBP, 2.14 (95% CI:1.21-3.81,p = 0.009) for homocysteine and 2.03 (95% CI:1.12-3.69, p = 0.020) for TC, respectively.

Conclusion:
In Tibetan plateau area, hemoglobin,SBP,homocysteine and TC were positively related with microalbuminuria in hypertensive patients.
Abstract P2072: Integrative Network Analysis Of Microbiome-Immune Axis In Metabolic Syndrome Patients During A Fasting Intervention
Authors: Avery Ellen G , Balogh András , Bartolomaeus Hendrik , Löber Ulrike , Steckhan Nico , Markó Lajos , Wilck Nicola , Hamad Ibrahim , Šušnjar Urša , Mähler Anja , Hohmann Christoph , Lesker Till R , Strowig Till , Dechend Ralf , Bzdok Danilo , Kleinewietfeld Markus , Michalsen Andreas , Müller Dominik N , Forslund Sofia K
Published: September 2019

Fasting can prolong survival and reduce disease burden in rodent models, and possibly in humans. The relationship between diet, gut microbiota, immune system and host (patho)physiology has only recently been explored, and information is lacking on how periodic fasting affects the gut microbiome in patients with metabolic syndrome (MetS). We show a 5-day fast (FAST) in humans, followed by a modified DASH diet is more effective than DASH alone (DASH) at reducing systolic blood pressure (SBP change measured by ABPM, 95% CI; FAST: [-7.053,-1.142], DASH: [-5.880,1.477]), need for antihypertensive medication (FAST: n=15 of n=35, DASH: n=6 of n=36 patients), and body-mass index at three months post intervention. Fasting altered the gut microbiome, impacting bacterial taxa and functional gene modules associated with the production of short-chain fatty acids (e.g.
Faecalibacterium prausnitzii
,
Eubacterium rectale, Coprococcus comes
), previously linked to vascular health and immunity. Immunophenotyping and cross-system analyses revealed that SBP changes correlated with circulating Il-2
+
TNFα
+
mucosa-associated invariant T (MAIT) cells (FDR-corr P(q) =0.044, Spearman’s rho=0.44), Il-17
-
IFNγ
+
MAITs (FDR-corr P(q) =0.022, Spearman’s rho=0.49), and effector CD4
+
T cells (FDR-corr P(q)=0.047, Spearman’s rho=0.43). By stratifying the fasting group into BP responders and non-responders, we identified a set of 76 microbial and 99 immune responder-specific features. Machine learning algorithms could predict long-term SBP responsiveness from baseline immunome data, identifying changes in effector CD8
+
T cells, Th17 cells and Tregs as discriminators (Single-subject prediction: 71%). This is the first high-resolution multi-omics characterization of fasting in MetS. Fasting induced long-term reduction in body weight and SBP, accompanied by changes in microbiome and immune homeostasis. Our data implicate fasting as a promising non-pharmacological intervention in MetS.
Abstract P3001: Disruption of Endothelial BBSome Causes Vascular Dysfunction and Hepatosteatosis
Authors: Jiang Jingwei , Reho John , Morgan Donald , Rahmouni Kamal
Published: September 2019

Almost every single cell in the human body possesses primary cilium. The primary cilium function as a sensor of blood flow and sheer stress and contribute to both calcium and nitric oxide signaling in the endothelium. The BBS1 protein is an important member of the BBSome complex which mediates protein trafficking to the cilia membrane and other cellular compartments. To investigate the role of the BBSome in endothelial cells, we generated mice lacking the
Bbs1
gene specifically in endothelial cells by crossing the Bbs1
fl/fl
mice with the endothelial-specific Tie2
cre
mice. The Bbs1
fl/fl
/Tie2
Cre
mice developed normally compared to littermate controls. We assessed vascular function
ex vivo
using aortic rings and resistance-sized mesenteric arteries. Interestingly, loss of the
Bbs1
gene in endothelial cells caused endothelial dysfunction with a more severe effect in female mice as indicated by the impaired acetylcholine (ACh)-induced relaxation (Max relax of mesenteric artery: males: 43.6±7.6% vs 56.4±6.2% in controls, P<0.05; females: 35.8±8.0% vs 75.9±10.0% in controls, P<0.05). Of note, the relaxation responses evoked by sodium nitroprusside in both the aorta and mesenteric artery were not different in male and female Bbs1
fl/fl
/Tie2
Cre
mice, indicative of endothelial but not smooth muscle dysfunction in the endothelium-specific Bbs1 null mice. Blood pressure tended to be elevated in Bbs1
fl/fl
/Tie2
Cre
mice particularly females. Strikingly, endothelial
Bbs1
gene deletion caused hepatosteatosis as indicated by the significant lipid deposition in the liver of Bbs1
fl/fl
/Tie2
Cre
mice by oil-red-O staining (females: 7.75±2.34 vs 0.59±0.16 % area in controls, P<0.05; males: 1.67±0.62 vs 0.40±0.09 in controls, P<0.05). Lipid extraction revealed a 2-6-fold increase in triglycerides and cholesterol in the liver of Bbs1
fl/fl
/Tie2
Cre
mice. Consistent with this, Bbs1
fl/fl
/Tie2
Cre
mice exhibited 80-90% reduction (P<0.05) in the expression of liver fatty acid transport and binding protein (Fatp2 and Fabp1). Thus, we conclude that the endothelial BBSome is required for the control of vascular endothelial function and hepatic lipid metabolism.
Abstract P3005: P66shc Plays a Role in Aldosterone Induced Vascular Remodeling and Dysfunction
Authors: Ucci Sarassunta , Battistoni Allegra , Nicoletti Carmine , Filippini Antonio , Montezano Augusto C , Volpe Massimo , Touyz Rhian M , Savoia Carmine
Published: September 2019

Objective:
This study sought to investigate whether aldosterone may induce vascular functional and structural alterations in part through p66shc-dependent processes.

Design and method:
P66shc
-/-
mice (14 weeks, 6 per group) and age-matched wild type (WT) control mice were treated or not with aldosterone (300 μg /kg/ day) for 4 weeks. Systolic blood pressure (SBP) was measured by tail-cuff method. Endothelium-dependent and independent relaxation was assessed by concentration-response curves to acetylcholine ± L-NAME (100 μM) and sodium nitroprusside (SNP) respectively, in mesenteric arteries pre-contracted with norepinephrine (10 μM). Media-to-lumen ratio (M/L) and cross sectional area (CSA) were evaluated in vessels as pressurized preparations. Reactive oxigen species (ROS) production was evaluated by DHE staining in aorta. Nox 1 expression was evaluated by immunoblotting.

Results:
SBP was similar in WT and p66shc
-/-
mice before treatment and was significantly increased after aldosterone treatment in both WT (192.3±4.522 vs 103.3±2.996; p<0.05) and p66shc
-/-
mice (176.8±5.313 vs 105.3±1.542; p<0.05). However SBP increase was significantly blunted in p66shc
-/-
mice treated with aldosterone as compared to WT treated mice (176.8±5.313 vs 192.3±4.522, p<0.05). Acetylcholine-induced vasodilation was similar in WT and p66shc
-/-
mice and was significantly reduced only in WT after treatment. Acetylcholine induced relaxation was blunted by L-NAME in all the groups although at less extent in WT. Endothelium-independent vasodilation was similarly preserved in all the groups. M/L ratio was similar in both WT and p66shc
-/-
before treatment and was significantly increased by aldosterone only in WT group (p<0.001). CSA was similar in all the groups. Both ROS production and NOX-1 expression were similar in WT and p66shc
-/-
mice and were significantly increased after treatment only in WT (+20% and +2,5 fold respectively, P<0.05).

Conclusions:
Despite BP increase, aldosterone induced endothelial dysfunction and vascular remodeling with associated increased oxidative stress in WT but not in p66shc
-/-
mice. Thus, p66shc may play a role in molecular mechanisms of endothelial dysfunction and vascular remodeling in aldosterone-induced hypertension.
Abstract P3018: Sirt3 Depletion in Human Essential Hypertension is Linked to Vascular Inflammation and Oxidative Stress While Endothelial Specific Sirt3 Depletion in Mice Promotes Vascular Dysfunction and Increases Hypertension
Authors: Dikalova Anna , Pandey Arvind , Xiao Liang , Lopez Marcos G , Billings Frederic T , Verdin Eric , Auwerx Johan , Harrison David G , Dikalov Sergey
Published: September 2019

Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of adult population. Vascular dysfunction is crucial in hypertension pathophysiology and exhibits bidirectional relationship. Metabolic disorders and oxidative stress contribute to vascular dysfunction, and mitochondrial deacetylase Sirt3 is critical in the regulation of metabolic and antioxidant functions. We hypothesized that reduced Sirt3 expression contributes to vascular dysfunction and essential hypertension. We studied Sirt3 in arterioles from human mediastinal fat in patients with essential hypertension compared with normotensive subjects. Pathophysiological role of vascular Sirt3 depletion was studied in mice with tamoxifen-inducible endothelial specific Sirt3 depletion (Ec
Sirt3KO
). For the first time, we showed a 40% decrease in vascular Sirt3 level and 400% increase in SOD2 acetylation in hypertensive subjects which was linked to increased oxidative stress measured by superoxide overproduction and vascular inflammation due to elevated NfKB activity, VCAM, ICAM and MCP-1 levels. Interestingly, global Sirt3 depletion in mice increases blood pressure, inactivates key mitochondrial antioxidant SOD2 due to acetylation, increases vascular p65, VCAM, ICAM and MCP1, and increased T cell infiltration in kidney, induces cell-senescence and promotes vascular aging while global Sirt3 overexpression prevents these deleterious effects. We tested if Ec
Sirt3KO
mice have vascular dysfunction and hypertension. Both basal and angiotensin II-induced blood pressure was increased in Ec
Sirt3KO
mice accompanied by endothelial dysfunction and vascular O
2

•

overproduction. Treatment of Ec
Sirt3KO
mice with SOD2-mimetic mitoTEMPO reduced vascular inflammation, markers of cell-senescence and vascular aging to the wild-type control levels while treatment of Ang II-infused Ec
Sirt3KO
mice partially rescues from vascular inflammation and attenuates accelerated vascular aging. We suggest that Sirt3 depletion in hypertension promotes both endothelial oxidative stress and metabolic dysfunction. Our data support a therapeutic potential of targeting Sirt3 expression in vascular dysfunction and hypertension.
Abstract P3019: Endothelial Epithelial Sodium Channel is a Novel Mediator of Early Macrovascular and Microvascular Stiffening That Precedes Kidney Injury in Diet-Induced Obesity
Authors: Aroor Annayya , Youxin Xiong , Jia Guanghong , Habibi Javad , Yan Yang , Manrique Camila , Lastra Guido , Dongqing Chen , Zhe Sun , Martinez-Lemus Luis , Ramirez-Perez Francisco , Hill Michael , DeMarco Vincent , Jaisser Frederic , Sowers James , Whaley-Connell Adam
Published: September 2019

Consumption of a Western Diet (WD) high in saturated fat and refined carbohydrates causes obesity and leads to insulin resistance and associated vascular stiffening in females earlier than males. This diet-induced obesity is characterized by enhanced activation of vascular mineralocorticoid receptors (MRs). Our recent work suggests that enhanced MR signaling in female mice prompts increased expression and translocation of the α-subunit of the epithelial sodium channel to the endothelial cell (EC) surface (EnNaC). However, the influence of EnNaC on endothelial function in the kidney remains unknown. Therefore, we hypothesized that WD feeding would induce kidney microvessel dysfunction and kidney injury through inflammatory pathways. Using a model of cell specific deletion of the α-subunit of EnNaC, female KO mice and littermate controls were fed a diet high in fat (46%) and fructose (17.5%) for 12 weeks. There were increases in indices of weight gain and fat mass in WD fed mice along with increased measures of central aortic stiffness, renal arteriolar remodeling, perivascular fibrosis and aortic and kidney endothelial stiffening in the absence of increases in blood pressure or proteinuria. The central aortic stiffness, renal arteriolar remodeling, perivascular fibrosis and aortic and kidney endothelial stiffening occurred in temporal relation to reductions in bioavailable nitric oxide. All of these abnormalities were attenuated in the EnNaC α-subunit knockout (endothelial stiffness, WD, 9.2 ± 0.65 kPA; WD-KO, 5.38 ± 0.75kPA). Our observations suggest, that central aortic and kidney vessel stiffening along with arterial wall remodeling occur in conjunction to renal injury.
Abstract P3023: Contribution Of Transcription Factor EB-mediated Autophagy In Vascular Smooth Muscle Cell Dedifferentiation And Neointimal Injury
Authors: Wang Yun-Ting , Li Xiang , McConnell Bradley K , Li Pin-Lan , Zhang Yang
Published: September 2019

Autophagy is recently implicated in regulating vascular smooth muscle cell (SMC) homeostasis and in the pathogenesis of vascular remodeling. Transcription factor EB (TFEB) is a master regulator of autophagy signaling pathways. However, the molecular mechanisms and functional roles of TFEB in SMC hemostasis have not been elucidated. Here, we surveyed the ability of TFEB to regulate autophagy pathway in SMCs, and whether pharmacological activation of TFEB favors SMC homeostasis preventing SMC dedifferentiation and pathogenic vascular remodeling. In primary cultured SMCs, TFEB activator trehalose induced nuclear translocation of TFEB (increased by 55.6±5%) and consequent upregulation of TFEB-controlled autophagy genes including LC3 (by 90.6±15%) and p62 (by 45±5%). Moreover, trehalose suppressed serum-induced SMC dedifferentiation to synthetic phenotypes as characterized by inhibited proliferation and migration. These effects of trehalose were mimicked by ectopic upregulation of TFEB in SMCs. In animal experiments, partial ligation of carotid arteries for 2 weeks induced down-regulation of TFEB (by 40±3.5%) and its downstream genes in the media layer of these arteries. Such TFEB suppression was correlated with increased SMC dedifferentiation and aggravated high fat diet (HFD)-induced neointima formation (intima area: ND 2.1±0.2 μm2 vs. HFD 10.2±2.8 μm2). Treatment of mice with trehalose reversed this TFEB pathway suppression, and prevented SMC dedifferentiation and HFD-induced neointima formation. In conclusion, our findings have identified TFEB as a novel positive regulator for autophagy pathway and cellular homeostasis in SMCs. Our data suggest that suppression of TFEB may be an initiating mechanism that promotes SMC dedifferentiation leading to accelerated neointima formation in vascular disorders associated with metabolic stress, whereas trehalose reverses these changes. These findings warrant further evaluation of trehalose in the clinical settings.
Abstract P3026: Impact of Dietary Electrolytes on Post-Nephrectomy Blood Pressure, Proteinuria and Renal Function
Authors: McDonough Alicia A , Lei Hillmin , Priver Taylor S , McFarlin Brandon E , Smith Scotti D , Pastor-Soler Nuria , Ralph Donna L
Published: September 2019

When chronic kidney disease progresses to end stage renal disease, the optimal treatment is living kidney donation (LKD). A 10 yr prospective study of 1214 donors (PMID 27006347), reported that LKD increased risk of hypertension (HTN), by 3.64-fold, as well as HTN induced albuminuria.
Our objective
was to test whether a DASH-style diet (DD: 0.74% NaCl, 3%K with 1% each: Cl
-
, citrate, HCO
3
-
) would blunt hypertension and albuminuria following UNX vs. a western style diet (WD: 2% NaCl, 1%KCl). Uninephrectomized (UNX) male SD rats (n=5/group) preequilibrated on diets were analyzed 12-14 wks post-UNX.

Systolic BP (SBP, mmHg) was similar pre-UNX in DD (126 ± 8) and WD (132 ± 8); SBP increased post-UNX by 7 ± 2 (DD) and 21 ± 5 (WD) mmHg, p=0.04. Urine injury markers (albumin, angiotensinogen, KIM-1 and plasminogen) increased in both DD and WD (all p<0.01). Kidney weight increased similarly from 1.5 ± 2 (pre-UNX) to 2.3 ± 0.2 g (post-UNX) in pooled DD, WD. By IHC, glomeruli diameters increased 1.6-fold pre-vs. post-UNX.

Transporter profiles were generated from both pre-and post-UNX kidneys. Pre-UNX, DD (vs. WD) exhibited lower abundance of proximal tubule (PT) NHE3, NaPi2 and NHERF1, and higher abundance of NKA α1, NCC, NCCp, claudin 7, SPAK, ENaC subunits and AQP2 (all p < 0.01). Post-UNX (vs. pre-UNX) abundance, normalized to equivalent protein, exhibited lower claudin2, megalin, AQP1 and AQP2 in both DD and WD (all p < 0.01), and, specifically to DD post-UNX: 1.4-fold increases in NCCp, SPAKp and 0.7-fold decreases in cleaved α and γ ENaC (all p<0.05). By IHC, NHE3 localized within the apical microvilli in DD and WD pre- and post-UNX. Lithium clearance (CLi, ml/min/Kg BW) increased post-UNX in DD (p=0.006) not WD; post UNX CLi was higher in DD (0.075 ± 0.013) vs WD (0.042 ± 0.009), p=0.036.

In conclusion, the phenotype of HTN and proteinuria observed following LKD in humans is evident in this pilot SD rat study. Compared to the 2% NaCl/1% KCl “Western style” diet, the 3% K
+
and alkali rich “DASH style diet” lowered baseline PT transporter levels, increased CLi (indicator of flow out of PT), elevated distal Na
+
transporters (likely due to flow from PT) and blunted the rise in BP post-UNX. The findings suggest that DASH style dietary electrolytes may improve outcomes following LKD.
Abstract P3030: Lower 24- Hour Urinary Sodium Excretion is Associated With Hypertension Control: The 2010 Heart Follow-Up Study
Authors: Elfassy Tali , Chamany Shadi , Bartley Katherine , Yi Stella , Angell Sonia
Published: September 2019

Background:
Among individuals with hypertension (HTN), controlling high blood pressure (BP) reduces the risk for cardiovascular events and death. Reducing dietary sodium can help achieve BP control. The study aim was to use a population-based sample utilizing the gold-standard for urinary sodium to quantify the degree to which sodium was independently associated with BP control among individuals with HTN.

Methods:
Participants included 1,568 adults from the Heart Follow-Up Study, a New York City population-based representative study conducted in 2010. Participants collected urine for 24 hours and had BP and other anthropometrics measured. HTN was defined as systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, or being on BP lowering medication. Sodium intake (mg/day) was measured from 24-hour urine.

Results:
HTN prevalence was 30.8%. Among those with HTN (n=560), 64.6% were aware, 56.3% were treated, and 40.3% were controlled. Among those treated for HTN (n=423), 62.9% were controlled. Mean sodium intake among those with HTN was 3,564 mg/day. From multivariable adjusted logistic regression models, each 500mg decrement in 24-hour urinary sodium excretion was associated with a 18% higher odds of HTN control among those with HTN (1.18, 95% CI: 1.07, 1.30).

Conclusions:
In New York City, approximately one in three people has HTN with a majority uncontrolled. Sodium intake among those with HTN was 55% greater than the recommended upper limit of 2,300 mg per day. Among individuals with HTN, lower sodium intake was associated with HTN control.
Abstract P3032: Low-Salt and Minimal Sugar-Sweetened Beverage Intake May Not Improve Hypertension Control
Authors: Umanath Kausik , Hassett Clare , She Ruicong , Adrianato Indra , Levin Albert , Ortiz Pablo , Yee Jerry
Published: September 2019

Objective:
Sugar-sweetened beverage (SSB) (high fructose corn syrup and sucrose) consumption positively associates with obesity, cardiovascular disease, and hypertension (HTN). High fructose intake may aggravate HTN, an effect enhanced by greater sodium intake. Thus, high SSB may increase difficult-to-control BP (BPD).

Methods:
SSB consumption in the Systolic Blood Pressure Intervention Trial (SPRINT) was evaluated in 61 subjects with a validated instrument and converted to grams of fructose per day. Demographics and 24-hour sodium excretion were collected. The BPD group had SBP >140 mmHg or >120 mmHg for intensive group participants,

or

BP at “goal” for the trial group and more than median number of agents in each group in study as a whole. The “BP Easy” group (BPE; n=25) group comprised the remainder of subjects. Mean BP from two visits before SPRINT termination established the study BP; descriptive variables were summarized; and a Wilcoxon rank sum test was used to compare SSB consumption between groups.

Results:
Cohort characteristics are shown in Table 1. BPD and BPE median fructose intakes were 11.25 g/d (IQR, 5.5 to 17.92) and 11.9 g/day (IQR 2.9 to 36.71;
P
=0.577), respectively. BPD and BPE median 24hr urine sodium excretion were 108.4 mmol (IQR 89.5-152.5) and 121.1 (102-137; P=0.16), respectively.

Conclusions:
A highly selected group of older subjects had low SSB (fructose) intake, yet a proportion that consumed less sodium and fructose manifested difficult to control BP. Further study of this sub-population is critical to better understanding difficult to control BP.
Abstract P3035: Role of T Cells in Sex Differences in Blood Pressure Elevation and Adipose Tissue Expansion Following Chronic High Fat Diet Feeding in Dahl Rats
Authors: Elmarakby Ahmed A , Mohamed Riyaz , Ramirez Lindsey , Snyder Elizabeth , Sullivan Jennifer
Published: September 2019

Diets high in saturated fats are increasingly linked to the development of hypertension, yet the mechanisms by which high saturated fat diet (HFD) increases blood pressure remain unclear. Although young women are typically protected from hypertension relative to age-matched men, recent studies suggest that the cardiovascular protection in young women is compromised by chronic consumption of a HFD. We hypothesize that chronic HFD treatment causes a greater increase in blood pressure in females via sex-specific activation and recruitment of T cells and adipocyte expansion. Male and female Dahl rats (n=4-5) were placed on HFD at 8 wks of age. After 4 wks of HFD, blood pressure (BP) significantly increased in male and female Dahl rats to a comparable degree. Although BP continued to increase over the course of 10 wks of HFD treatment, female rats have a greater increases in BP (~40 mmHg increase in BP) after 10 weeks of HFD vs. males (~20 mmHg increase in BP). Fat pad weight and adipose tissue expansion increased in WT rats of both sexes following 10 wks of HFD treatment, yet females exhibited greater increases in fat pad weight and adipose tissue expansion vs. males. To determine whether T cells contributes to sex differences in BP elevation in Dahl rats fed HFD, we utilized Dahl rats lacking CD247 which encodes the T cell receptor CD3 chain that is required for T cell signaling. 10 wks of HF feeding did not change BP in either sex of Dahl CD247 KO rats. There were attenuated increases in fat pad weight and adipocyte expansion in Dahl CD247 KO rats and females exhibited more pronounced attenuations than males. Flow cytometric analysis revealed that HFD decreased Tregs and increased Th17 cells in both sexes of Dahl WT rats and females on HFD had the most pro-inflammatory T cell profile indicted by the Th17 cells:Tregs ratio. Our data suggest that greater adipocyte expansion with a HFD feeding in female Dahl rats vs. male might result in greater recruitment and activation of pro-inflammatory T cells and larger increases in BP.
Abstract P3036: Calcitonin Gene Related Peptide Release From Afferent Nerve Fibers of the Skin is Influenced by Salt Intake
Authors: Ditting Tilmann , Rodionova Kristina , Reeh Peter , Ott Christian , Schmieder Roland , Schiffer Mario , Amann Kerstin , Veelken Roland
Published: September 2019

Sodium can be accumulated without commensurate water retention in the skin (non-osmotic sodium storage). Macrophages play a pivotal role in this context and their depletion can induce salt-sensitive hypertension (ssHTN). On the other hand renal afferent peptidergic nerves are involved in ssHTN. Since the skin is also densely innervated by afferent peptidergic nerves we hypothesized that high salt diet might enhance the release of neuropeptides from these nerve fibers. In a cross-over design, two groups of rats (n=6, each) were fed either low salt diet (LS; 0.2%) with free access to tab water for 14 days or high salt diet (HS; 8%) with free access to 0.9% saline as drinking water. After 14 days a skin sample (3x3mm) of the groin area was excised, and the diet was switched for another 14 days. Then a contralateral skin sample was taken. Tissue analyzed in an organ-bath and calcitonin gene related peptide (CGRP) content in the supernatant was measured with ELISA. After two baseline measurements within 5 min, the tissue was superfused with hypertonic saline (4.5%) for 5 min, and three further samples of the supernatant were taken every 5 min. Baseline CGRP release was similar with both diets (LS 11.9±1.5 vs HS 13.6±1.5ng/g skin). Maximum release was higher with HS diet (LS 17.5±1.8 vs HS 29.8±1.3ng/g skin; P<0.05). After diet switch the results were similar: baseline LS 9.4±1.2 vs HS 10.1±, however, in rats previously on HS diet release tended to be higher with LS diet, nevertheless with HS diet the release was higher again (LS 19.7±2.1 vs HS 29.3±1.7; P<0.05). High sodium diet sensitized neuropeptide release from peptidergic sensory nerves in the skin. Hence peptidergic afferent nerves might be an integrated body-wide system involved in sodium handling in very different target areas like skin and kidney. Putative peptidergic mechanisms (vasoregulation, chemotaxis) remain to be determined in this respect.
Abstract P3041: Maternal Hypertension Sensitizes Post Weaning High Fat Diet Elicited Hypertension in Adult Offspring
Authors: Xue Baojian , Beltz Terry G , Guo Fang , Johnson Alan K
Published: September 2019

Our previous studies showed that maternal hypertension sensitizes angiotensin (ANG) II-induced hypertension and this sensitization is associated with upregulation of renin-angiotensin system (RAS) components and proinflammatory cytokines (PICs) in the brain cardiovascular nuclei. In this study, we investigated whether the offspring from mothers with maternal hypertension had a sensitized hypertensive response elicited by high-fat diet (HFD) feeding for 12 weeks beginning from the time of weaning. In both male and female offspring, basal mean arterial pressure (MAP) in normal-fat diet (NFD) feeding offspring of either normotensive (NT; males, 112.3±2.2; females, 109.0±1.5 mmHg) or hypertensive (HT; males 112.4±1.0; females 108.4±1.3 mmHg) dams were comparable. HFD feeding significantly elevated MAP in both male and female offspring. However, the increases in MAP were greater in offspring of HT dams (males, 128.0±2.3 mmHg; females, 121.0±1.8 mmHg) than that in the offspring of NT dams (males, 120.8±1.4 mmHg; females, 115.3±1.2 mmHg). Ganglionic blockade (hexamethonium, ip) produced a greater reduction fall in MAP only in male HFD-fed offspring when compared to NFD-fed offspring of either NT dams (-45.2±3.4 vs. -20.9±4.1 mmHg) or HT dams (-41.2±6.7 vs. -26.6±2.5 mmHg), suggesting that HFD feeding elicited an increased sympathetic tone in males, but not in females. In lamina terminalis tissues, RT-PCR analyses revealed that HFD feeding in both male and female offspring of HT dams led to a significant increase in mRNA expression of several components of the RAS and PICs (males, leptin, ACE, NOX2 and TNF-α; females, leptin, AT1R, NOX2 and TNF-α). However, maternal hypertension resulted in a significant increase in mRNA expression of leptin and AT1R only in male offspring fed NFD when compared with NFD offspring of NT dams. The results indicate that maternal hypertension sensitized HFD-elicited HT in both male and female adult offspring, but in a sex-specific manner associated with altered sympathetic tone and expression of RAS components and PICs in the brain.
Abstract P3044: Second Trimester Severe Fetal Growth Restriction Preceding Preterm Severe Hypertensive Disorder in Pregnancy
Authors: Shields Andrea D , Wagner Richard , Battistelli Jacqueline , de Assis Viviana
Published: September 2019

Background:
Pregnancies complicated by hypertensive disorders are at risk of fetal growth restriction, abruption, and stillbirth. These complications are likely mediated through endothelial vascular disease of the placenta.

Case:
A 34 year old female G3P0111 with a history of HELLP syndrome was referred for severe fetal growth restriction at 23 weeks and 3 days. She was normotensive with normal fetal anatomic survey, low risk cell free DNA screen, negative antiphospholipid antibody panel and no evidence of TORCH infections. She returned to the clinic two weeks later with new onset hypertension, suboptimal interval fetal growth and oligohydramnios. She was admitted, and delivered at 25 weeks and 5 days for preeclampsia with severe features. Her female infant weighted 340 grams, and was intubated and admitted to the NICU. The NICU stay was complicated by respiratory distress syndrome, cholestasis, pancreatic insufficiency, dyschezia, growth failure, hydronephrosis, and vesicoureteral reflux. Today she is 12 months old and thriving. Placental pathology showed accelerated villous maturation suggestive of placenta underperfusion, consistent with clinical history of preeclampsia.

Discussion:
Preeclampsia is a complication of pregnancy typically characterized by elevated blood pressure and damage of other organs, most commonly the liver or kidney. While the exact mechanisms that cause preeclampsia are not known, the resultant endothelial vascular disease affecting the placenta can lead to fetal growth restriction or abruption. Second trimester fetal growth restriction can result from fetal aneuploidy, viral infections, or maternal conditions that lead to uteroplacental insufficiency such as chronic hypertension or pre-gestational diabetes. Few cases describe fetal growth restriction preceding the onset of preeclampsia, although this is not uncommon in clinical practice.

Conclusion:
Pregnancies complicated by severe, preterm fetal growth restriction preceding the development of hypertensive disorder appear to have a common etiologic pathway, and the absence of hypertension does not exclude the possibility of underlying preeclampsia. Increased vigilance for signs and symptoms of preeclampsia in these pregnancies is warranted.