bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P105: Redox Modulator Akt-1005 Alleviates Oxidant Stress In An
In Vitro
Model Of Preeclampsia
Authors: Pintye Diana , Lo Agnes , Salahuddin Saira , Karumanchi Ananth A , Zsengeller Zsuzsanna K
Published: September 2022

Background:
Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5-7% of all pregnant women, and there is no effective treatment available. Early abnormal placental development is associated with oxidative stress and the release of reactive oxygen species in the placenta. This phenomenon leads to downstream signaling and production of anti-angiogenic factors, which cause endothelial and trophoblast dysfunction and the cardinal features of PE, i.e., hypertension, proteinuria, and in severe cases, eclampsia. Our group developed a novel series of redox modulators and sought to test if these compounds can effectively reduce placental oxidative stress and mitigate PE symptoms
in vitro
.

Methods:
We induced
in vitro
oxidant stress in human villous explants with 2% O
2
and assessed whether augmenting cell-redox function with the proposed compound AKT-1005 reduced (i) cell injury (cell cytotoxicity assay), (ii) mitochondrial stress (mitochondrial -derived superoxide production, mitochondria dysfunction) (iii) production of the transcription factor HIF1A and (iv) downstream anti-angiogenic responses (sFLT1 production). These effects were compared with reference antioxidants i.e., Vit C and MitoTEMPO.

Results:
In our villous explant assays, pretreatment with the AKT-1005 reduced mitochondrial-derived ROS production in hypoxia-exposed trophoblasts cells, indicating that the key factor in the development of PE, the oxidant stress, can be alleviated by the redox modulator compound. The AKT-1005 pretreatment also reduced HIF-1A expression and sFLT1 protein expression in hypoxia-exposed villous trophoblast cell, with better efficacy than Vit C and MitoTempo. Furthermore, AKT-1005 improved the mitochondrial electron chain enzyme activity in the stressed explant culture, mainly in syncytiotrophoblast cells, which is another promising characteristic of the applied antioxidant molecule.

Conclusion:
In reducing placental trophoblast oxidative stress, redox modulators present a potential novel therapeutic approach for the treatment of preeclampsia. Future investigation is warranted regarding the
in vivo
use of these compounds.
Abstract P108: Compensatory Changes In Metabolomic Profiles In The Kidney Of Sprague-dawley Rats Fed A High-salt Diet.
Authors: Shimada Satoshi , Hoffmann Brian R , Greene Andrew S , Liang Mingyu , Dash Ranjan K , Cowley Allen W
Published: September 2022

Goal:
The effects of a high salt diet on renal cortical (
Cx
) and outer medulla (
OM
) tissue metabolism of normal age matched male Sprague-Dawley rats (SD; 15-16 wk age; n-5) was determined with rats fed 0.4% NaCl (LS) and after switching to 4.0% NaCl (HS) diet at day HS14 and HS21.

Methods:
From snap-frozen Cx and OM tissue, novel analytical approaches were developed and applied at the JAX lab to determine metabolic profiles using 4 modes (C18+/- and HILIC+/-) using a Thermo Q-Exactive Orbitrap coupled to a Vanquish UPLC system.

Results:
Kidney weight was increased (P<0.05) by 0.5 mgkw/gbw at HS14 from from LS level of 3.2±0.1 mgkw/gbw and remained constant at HS21. A principal component analysis (PCA) of each mode found distinct separation of metabolites in both the Cx and OM comparing LS to HS14, and HS21. Of 2085 named compounds identified in Cx and 1886 in OM, the Metaboanalyst database found 968 (Cx) and 861 (OM) with 285 (Cx) and 284 (OM) changed (P<0.05) at HS14. At day HS21, 438 were changed (P<0.05) in Cx and 349 in OM compared to LS. A pathway enrichment analysis (SMPDB) of those metabolites was carried out. Expressed as the enrichment ratio (ER; observed hits/expected hits) found enrichment of Arachidonic acid metabolism pathway at HS13 (ER=2.7), consistent with observed increases (P<0.05) of L-glutamic acid, arachidonic acid and thromboxane B2. Increased levels of phosphoenalpyruvic acid and glucose 1-phosphate were observed (p<0.05), consistent with elevated glycolysis and gluconeogenesis, not observed at HS21. In the OM at HS14, the “Tyrosine metabolism” (ER:1.9), “Lysine degradation” (ER:2.2) and “Beta-alanine metabolism” (ER:1.9) pathways were enriched (P<0.05). Lysine, tyrosine and glutamate levels were reduced (P<0.05) indicating increased amino acid utilization. Also found were reductions of glucose-6-phosphate, pyruvate and alpha-ketoglutarate (P<0.05) indicating reduced glycolysis and TCA activity. At day HS21 these changes were generally not significant in either Cx or OM.

Conclusion:
Kidney weight increased after 2 wks of HS diet which was associated with increased amino acid metabolism and reduced glycolysis in OM (e.g. anabolic profile). Those metabolites (above) then returned to levels observed on a LS diet as kidney weight stabilized.
Abstract P111: Deletion Of Na
+
/H
+
Exchanger 3 Selectively In The Proximal Tubules Doesn’T Prevent The Development Of Doca-salt Hypertension In Pt-

Nhe3
-/-

Mice
Authors: Oliveira Leite Ana Paula , Li Xiao C , Hassan Rumana , Zhuo Jia L
Published: September 2022

We have previously shown that genetic deletion of Na
+
/H
+
exchanger 3 (NHE3) selectively in the proximal tubules lowered basal blood pressure and attenuated the development of angiotensin II (Ang II)-induced hypertension by promoting the pressure-natriuresis response. However, it is not known whether deletion of the NHE3 gene selectively in the proximal tubules attenuates salt-sensitive hypertension induced by DOCA-Salt. In the present study, we tested the hypothesis that the development of DOCA-Salt hypertension is attenuated by genetic deletion of NHE3 selectively in the proximal tubules of the kidney. To test the hypothesis, mice with proximal tubule-specific deletion of NHE3, i.e., PT-

Nhe3
-/-

, were generated using the iL-
Sglt2-Cre
/

Nhe3
flox

approach. Adult male PT-

Nhe3
-/-

mice were treated with or without DOCA (10 mg/10 g body wt., subcutaneously), supplemented with 2% high salt diet, for 4 weeks. Basal and weekly systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) were determined using the indirect tail-cuff method, whereas 24 hr. urinary sodium, potassium, and chloride excretion were determined using a metabolic cage. Compared with the time-control group (n=12), treatment with DOCA-salt moderately but significantly increased systolic SBP from 96 ± 3 mmHg to 126 ± 5 mmHg in PT-

Nhe3
-/-

mice (n=8;
P
<0.01). DBP and MAP increased to similar extents in response to DOCA-salt treatment (
P
<0.05). As expected, DOCA-salt hypertension significantly increased the pressure-natriuresis response, i.e., 24 hr. urinary sodium excretion by 55% (Control: 152 ± 19
vs.
DOCA-Salt: 236 ± 2 μmol/24 hr;
P
<0.01), potassium excretion by 52% (Control: 147 ± 16
vs.
DOCA-Salt: 224 ± 18 μmol/24 hr;
P
<0.01), and chloride excretion by 71% (Control: 181 ± 27
vs.
DOCA-Salt: 310 ± 31 μmol/24 hr;
P
<0.01), respectively. Taken together, these data do not support our hypothesis and suggest that deletion of NHE3 selectively in the proximal tubules doesn’t prevent the development of DOCA-Salt hypertension in PT-

Nhe3
-/-

mice.
Abstract P117: MECHANISMS OF SIGNALING PATHWAYS TRIGGERED BY ANGIOTENSIN I CONVERTING ENZYME IN CHO ECA CELLS TREATED WITH CAPTOPRIL
Authors: Yokota Rodrigo , Leite Ana Paula de Oliveira , Faça Vitor Marcel , Casarini Dulce Elena
Published: September 2022

Renin-Angiotensin System (RAS) is a hormonal system associated with hydroelectrolytic homeostasis and blood pressure control. Angiotensin II (Ang II) is the main and most potent biologically active product in the system, which is produced by the action of Angiotensin Converting Enzyme (ACE) on Ang I. Dysregulation of RAS is an important factor in the development and progression of cardiovascular/renal diseases and diabetes. Experiments and clinical practice have shown that the use of an ACE inhibitor (ACEi) is an effective treatment to attenuate hypertension and diabetic renal damage. In addition, recently the use of ACEi has also been associated with the activation of signaling pathways thus suggesting that ACE can act as a signal transductional molecule. The purpose of this study is to demonstrate the proteins that are differentially regulated when CHO-ECA cells are treated with the ACE inhibitor, captopril. The CHO-ACE cells were cultured in DMEM-SILAC medium in different media: Medium with light chain lysine (LV), medium with heavy chain lysine (P), and control (CT), with DMEM-High Glucose medium. At the 75% confluency, the cells were deprived of serum and then stimulated with captopril (1μM) or vehicle for 2 and 5 minutes (min). CHO-ACE cells were also cultured for the assay analysis of the Kinase Array. ACE activity was determined spectrofluorimetrically using ZPhe-His-Leu as substrate. With the SILAC medium, it was not possible to detect the differently modulated proteins by captopril. The kinase array demonstrated that some signaling pathways were not modulated after Captopril (eg, MSK1/2 and CREB). Other kinases were positively modulated after 2 min stimulation (eg, AMPKa1, HSP27, Akt 1/2/3 T308) and 5 min stimulation (STATa/b, HSP60, b-Catenin) with Captopril. Our screening also has shown that some kinases were negatively modulated following Captopril (eg, p53, PLC-γ1, Pyk2, eNOS). ACE activity in cell lysate group was inexpressive when treated with captopril. Our results expanded the repertoire of kinases modulated by the binding of Captopril to ACE, as well as, the role of ACE as a receptor and the modulation of signaling pathways triggered by this binding, which may imply in the treatment of hypertension.
Abstract P121: Sensitivity And Specificity Of The Biobeat Watch In Monitoring Covid19 Patients: Preliminary Data
Authors: Pecchioli Valerio , Lomartire Nazzareno , Valente Lucia , Gemmiti Maria Paola , Corsi Maria Pia , Eisenkraft Arik , Pecchioli Lorenzo , Fedele Francesco
Published: September 2022

Background:
Connected health technology can enable healthcare professionals to provide multiple solutions to meet the growing demand of care and control of COVID-19 infected patients, by optimizing economic resources and extending the scope of monitoring beyond the hospital. An innovative mobile device, the BioBeat Watch®, developed in Israel, with an APP that can be downloaded directly to the Smart Phone, is characterized by sensors already validated according to the regulations of the Food and Drug Administration for vital signs, the ECG track and the European Society Hypertension for the detection of blood pressure.

Purpose:
Wearable medical devices and the BioBeat software platform are appropriate for use in different settings for the management of acute, chronic cardiovascular, respiratory and inflammatory pathology, a tool capable of early identification of the instrumental signs of deterioration even before the exclusively clinical recognition that becomes even more difficult if we consider the patients at home.The aim of this study is to test the sensitivity and specificity of the biobeat wearable system applied in patients with paucisymptomatic COVID-19 infection (group A) and in those with previous SARS-COV2 disease discharged from the hospital who still needed post-acute monitoring (group B) and compared with clinical control, managing to determine early the clinical signs of worsening.

Methods:
The data recorded by individual patients are systolic and diastolic blood pressure, heart and respiratory rate, peripheral oxygen saturation and body temperature. The criteria of deterioration or worsening of the clinical condition are represented by the need to hospitalize the patient, alteration of one of the criteria grouped in the ABCDE.

Results:
We calculated the sensitivity of the methodology related to the alerts detected and the outcome of the patients. Sensitivity was 86.3% with a 95% CI of 0.71 to 1.03 and a specificity of 7.7%.

Conclusions:
Continuous monitoring with biobeat watch showed a high sensitivity in detecting early any alerts predictive of worsening of the disease.
Abstract P122: Posterior Reversible Encephalopathy Syndrome Following Moderna M-RNA Booster Vaccination Secondary To Hypertension Vs Vaccine Adverse Effect?
Authors: McCullough Jocelyn , Ahmad Manal
Published: September 2022

Clinical Case:
A 76-year-old female presented to our ED with acute onset confusion, unsteady gait and blurry vision within 24 hours after receiving the m-RNA Moderna booster vaccine. Medical history: notable for uncomplicated hypertension on metoprolol. She was awake, oriented intermittently x 3, with periods of confusion, blurry vision and intermittent unsteady gait and normal speech without any focal motor or sensory deficits. BP=192/80 mmHg bilaterally. Labs: showed hypercalcemia with elevated vitamin D 25-OH. Hypertension was managed with home dose of metoprolol succinate 150 mg/day and hypercalcemia improved with IV fluids. On Day 3 the patient was found lying in bed unresponsive to sternal rub with motor twitching of left arm, seizure like activity. Transfer to ICU for BP =185/104mmHg, T = 100.8 F, airway protection and treatment with diazepam. Empirical antibiotics were started for presumed encephalitis. EEG demonstrated seizure foci in bilateral posterior quadrants. MRI imaging on day # 3 showed T2/FLAIR hyperintensities in the parieto-occipital lobes and pulvinar of the thalami suggestive of posterior reversible encephalopathy syndrome (PRES).

Discussion:
PRES syndrome is both a clinical and radiological diagnosis with neurological changes coupled with MRI FLAIR hyperintensities in the parietal, occipital and frontal bilateral areas. This condition has been associated with uncontrolled hypertension, endothelial injury and side effect from certain drugs. Her hypertension was aggressively managed with amlodipine, enalapril, and IV metoprolol to decrease cerebral perfusion pressure. Repeat MRI imaging on day #14 demonstrated resolution of the hyperintensities without episodic blurry vision, confusion and our patient's mentation improved. At her 7 weeks follow our patient continued to have residual deconditioning and could only follow 2 step commands. We emphasize the importance of timely diagnosis with MRI imaging and preventing delay in management with adequate anti-hypertensives to prevent irreversible neurological damage from PRES syndrome. We also encourage reporting similar findings to VAERS as we are unable to exclude a reaction to her m-RNA vaccine booster.
Abstract P124: Bainiku-ekisu Attenuates Cardiac Remodeling In Angiotensin Ii-infused Mice
Authors: Okuno Keisuke , Okuno Keiichi , Kuroda Ryohei , Cicalese Stephanie , OKUNO Yoshiharu , Kono Ryohei , MARUMOTO Shinsuke , Utsunomiya Hirotoshi , Eguchi Satoru
Published: September 2022

A fruit of the
Prunus mume
is a traditional and familiar food in Asian countries and is most often pickled or used to make wine and juice concentrate. Recently, Bainiku-ekisu, an infused juice concentrate of
Prunus mume
is attracting attention as a potential health promoting food. We previously reported that Bainiku-ekisu (BE) incubation attenuates the activation of growth-promoting signaling cascade induced by angiotensin II (Ang II) in cultured vascular smooth muscle cells (VSMC). However, whether BE has any effect on an animal model of cardiovascular disease remains unknown. Therefore, this study was designed to elucidate whether BE could attenuate cardiovascular pathology induced by Ang II infusion in mice, representing a model of human hypertension. 8- to 10-week-old male C57BL6 mice were randomly divided into four groups and infused with Ang II (1 μg/kg/min) for 2 weeks via osmotic mini-pump or sham-operated, and given 1% BE containing water (BEW) or normal water (control) for 2 weeks. Blood pressure was evaluated every other day by tail cuff measurement. Cardiac hypertrophy was assessed by heart-to-body weight ratio. After 2 weeks, mice were euthanized, and the aorta and heart collected. Extracted aortas and hearts were fixed and used for histological studies to evaluate vascular hypertrophy and perivascular fibrosis. Increase in heart-to-body weight ratios were unaltered by BEW. Aortic medial hypertrophy was observed in control mice (n=5) after 2 weeks of Ang II infusion, which was attenuated in BEW group (96 μm vs. 71 μm, respectively, p<0.01). Control mice with angiotensin II infusion showed cardiac perivascular fibrosis, which was attenuated in BEW group (fibrosis index score: 1.02 vs. 0.30, p<0.01). In addition, trend of hypertension attenuation by BEW was observed in Ang II-infused mice with BEW treatment. We also observed attenuation of DNA synthesis induced by AngII with BE incubation in cultured aortic fibroblasts. In conclusion, BEW prevented Ang II-induced cardiovascular remodeling such as vascular fibrosis. Potential cardiovascular health benefit to taking BE as a functional food should be further studied.
Abstract P126: FXR1 Regulates Vascular Smooth Muscle Cell Cytoskeletal Dynamics By Multiple Mechanisms
Authors: St Paul Amanda , Preston Kyle , Corbett Cali , Leigh Tani , Okune Rachael , Kelemen Sheri E , Eguchi Satoru , Haines Dale S , Autieri Michael
Published: September 2022

Introduction:
Hypertension is a major risk factor for cardiovascular disease and stroke. Optimally treated hypertensive patients have a 50% greater cardiovascular risk than untreated normotensive subjects, presenting a need for additional targets. Vascular smooth muscle cells (VSMC) play a critical role in vascular contractility and regulation of blood pressure. Fragile X-related protein (FXR1) is a muscle-enhanced RNA binding protein. In addition to containing mRNA binding domains, FXR1 has an agenet-like domain for protein-protein interactions and four WH2 motif domains to mediate actin dynamics. The structure of FXR1 supports its role in post-transcriptional regulation and though largely ignored, cytoskeletal dynamics via potential protein-protein interactions. This study will test the hypothesis that FXR1 regulates vascular contractility by RNA stability and protein interactions.

Results:
RNA immuno-precipitation sequencing (RIPseq) analysis in human VSMC identified that FXR1 binds to mRNA that participate in VSMC contractility and cytoskeletal reorganization, and FXR1 depletion decreases mRNA abundance and stability of these transcripts. Mass-spectrometry and co-immunoprecipitation identified that FXR1 interacts with members of the WAVE complex, a five-subunit protein complex involved in the formation of the actin cytoskeleton, including CYFIP1 (Cytoplasmic FMR1-interacting protein 1) and Actin Related Protein 2/3 complex (ARP2). The WAVE complex is activated by an ARP2-mediated interaction with Rac1, promoting actin remodeling and cytoskeletal reorganization in a GTP-dependent manner. FXR1 depletion decreases small GTPases RAC1 and CDC42 activation in VSMC. Additionally, FXR1 depletion decreases VSMC lamellipodia formation, adhesion, migration and collagen gel contraction. Novel, VSMC-specific FXR1 conditional knock out mice show decreased diastolic (P < 0.05) blood pressure at baseline compared to controls.

Conclusion:
These data are the first to suggest that FXR1 regulates mRNA stability of contractile proteins and interacts with members of the WAVE complex. Deletion of FXR1 abrogates VSMC cytoskeletal reorganization, resulting in a hypotensive phenotype in VSMC-specific conditional knockout mice.
Abstract P129: Increasing In SHR Aortic Distensibility During The Onset Of Hypertension: The Role Of Appropriate Normalization For Stress-Strain Measurements.
Authors: Montandon Ian S , Fontes Milene T , Waigi Emily W , Pernomian Laena , Costa Tiago J , Uline Mark J , Rossoni Luciana V , Webb R Clinton , McCarthy Cameron G , Wenceslau Camilla F
Published: September 2022

The gold standard of arterial stiffness measurements in isolated aorta is the stress-strain (SS) relationship. Stress and strain are second-order tensors measured as newtons over the oriented area and change in length over the original length, respectfully. Wall thickness and artery diameter are variables that can change the SS curve and should be normalized to the dimensions of the subject. However, previous studies have used standard structural dimensions to calculate SS for different conditions, which may lead to conflicting data. Therefore, we hypothesized that aorta from SHR, during the onset of hypertension, will present with an increase in SS, based on their unique structural dimensions. To test this hypothesis, thoracic aorta from male Wistar (W) (3-month-old; 284±9 g) and SHR (S) (3-month-old; 458 ± 7 g) rats were cut in 2 mm segments and mounted on Tissue Puller to test SS. The rings were normalized individually (Self parameters; W and SHR-S) or using parameters from control (SHR-W). SHR rings normalized by their own parameters reduced the elastic modulus (W: 2.1 ± 0.3 vs SHR-S: 1.6 ± 0.2; p = 0.07). When the same SHR rings were normalized by W parameters, the elastic modulus increased (W: 2.1 ± 0.326 vs SHR-W: 3.3 ± 0.4; p = 0.01). Overall, these data show that the absence of individualized normalization can skew stress-strain calculations of elastic modulus. In SHR, we suggested that during the development of hypertension, there are compensatory mechanisms increasing distensibility. However, after onset, this phenomenon evolves to an increase in stiffness. These data may be absent in the literature due to the improper normalization application.
Abstract P130: Specialized Pro-resolving Mediator, Lipoxin A4, Attenuates Age-dependent Vascular Damage
Authors: Montandon Ian S , Fontes Milene T , Uline Mark J , Webb R Clinton , McCarthy Cameron G , Wenceslau Camilla F
Published: September 2022

Chronic, low-grade inflammation that develops with advanced age is known as inflammaging. This phenomenon is associated with large artery stiffness in age-dependent hypertension. Specialized pro-resolving mediators (SPMs), including Lipoxin A4 (LXA4) and Resolvin D1 (RD1), are derived from essential fatty acids, and they act as immunoresolvents to reduce inflammation and increase the clearance of pathogens and dying cells. However, LXA4, but not RD1, acts on formyl peptide receptor 2, which is known to modulate actin filaments and resolve inflammation. Therefore, we hypothesized that Specialized pro-resolving mediators, would restore mechanical stress and distensibility in aorta from older rats. To test this hypothesis, thoracic aortas from male Wistar rats (3 and 6 months old) were cut into 2 mm rings and incubated in the presence or absence of RD1 or LXA4; both 10 nM for 24 hours. Stress-strain curves were calculated via Tissue Puller (560TP-II, DMT). The aortic rings from 6-month-old rats presented with increased stress when compared to aortas of the 3-month-old (Maximal stress: 2749 ± 190 mN/mm
2
vs 4207 ± 242 mN/mm
2
, respectively; p=0.0015). Interestingly, LXA4 reduced stress in aorta from 6-month-old rats (Maximal stress: 2514 ± 552 mN/mm
2
, p=0.0282). No changes were observed in aorta from 3-month-old rats after LXA4 treatment. Resolvin D1 did not change vascular mechanics in aorta from 3- or 6-month-old rats. Overall, these data suggest that even modest advances in age are related with changes in vascular mechanics of large arteries and LXA4 via FPR2 can decrease inflammaging-related vascular stiffness.
Abstract P133: Human Induced Pluripotent Stem Cells-derived Vascular Endothelial And Smooth Muscle Cells And Fractions Of Native Human Arterioles Exhibit Robust Expression Of Marker Genes
Authors: Pandey Rajan , Liu Yong , Liu Pengyuan , Wang Jingli , Huang Jing , Yang Chun , Mishra Manoj K , Therani Bhavika , Kidambi Srividya , Geurts Aron M , Rao Sridhar , Cowley Allen W , Widlansky Michael E , Greene Andrew S , Liang Mingyu
Published: September 2022

Human induced pluripotent stem cells (iPSCs) can be differentiated into vascular endothelial and smooth muscle cells (iEC and iVSMC). The defined genetic makeup and the ease of genetic engineering in multiple cell types on an isogenic background make these cells potentially powerful tools for studying molecular mechanisms underlying vascular function and disease. While several studies have characterized iEC and iVSMC and compared them with other cultured cells, no studies have analyzed these cells in conjunction with native human cells. In this study, we characterized iEC, iVSMC, and fractions of native human arterioles by examining large panels of marker genes. iEC and iVSMC were differentiated (n=4) from a custom-made iPSC line. Differentiated cells were sorted using VE-cadherin (
CDH5
) to obtain iEC (positive selection) and iVSMC (negative selection). Arterioles were isolated from adipose tissues obtained from 4 humans, and the endothelial and vessel remainder fractions were separated by scraping. RNA-seq was performed on all samples. We focused the analysis on 10 and 15 marker genes for EC and VSMC, respectively, that we curated from the literature. iEC exhibited robust expression of 9 of the 10 EC markers such as
CD34
(FPKM, 137±58),
PECAM1
(153±32), and
VWF
(44±7), while iVSMC had negligible expression of EC marker genes. Conversely, iVSMC exhibited robust expression of 11 of the 15 VSMC marker genes, while the expression of these genes in iEC was depleted by several fold. Eight of the 10 EC marker genes were enriched in the endothelial fraction of native arterioles by several fold compared with intact arterioles, while 12 of the 15 VSMC marker genes were substantially depleted in the endothelial fraction. EC marker genes were significantly depleted and VSMC marker genes enriched in the vessel remainder fraction. In summary, iEC and iVSMC, as well as endothelial and vessel remainder factions from native human arterioles, exhibit robust expression of large panels of EC and VSMC marker genes based on agnostic RNA-seq analysis. These novel findings indicate that iEC, iVSMC, and endothelial and vessel remainder factions of native human arterioles are relevant tools for studying molecular regulation in specific vascular cell types.
Abstract P135: Specialized Pro-resolving Molecular Pathway Is Impaired In Resistance Arteries From Hypertensive Rats.
Authors: Fontes Milene T , Edwards-Glenn Jonnelle , Costa Tiago , Waigi Emily , Pernomian Laena , Webb R Clinton , McCarthy Cam , Wenceslau Camilla F
Published: September 2022

Specialized pro-resolving mediators (SPMs), derived from essential fatty acids, are known to playa major role in the immune system, as immunoresolvents. SPMs reduce acute inflammatoryresponses and leads to the clearance of pathogens and dying cells. Although we have demonstratedthat lipoxin A4, biosynthesized from the 5-lipoxygenase (LOX-5), improved endothelium-dependent relaxation in resistance arteries from SHR, it is unknown if (1) SPMs molecularpathways are present in resistance arteries independent of immune system activation, and (2)whether this pathway is dysfunctional in SHR. We hypothesized that the synthesis and downstreamsignaling of LOX-5-derived SPMs are impaired in resistance arteries from SHR. Mesentericresistance arteries (MRA) from male SHR (14-weeks old, n=5) and Wistar Kyoto (WKY) (14-weeks old, n=4) were collected to assess protein expression using Western blotting analysis. SHR`sMRA showed an increase in COX-2 expression (400%) when compared to WKY (p<0.05),demonstrating an inflammatory state. However, there was a reduction in the total LOX-5expression (30%) (Fig.1). Interestingly, an 65% increase in phosphorylation of 5-LOX at Ser 271was observed in MRA from SHR (Fig. 1) Ser 271 is responsible for the pro-inflammatory effectsof LOX-5, leading to a reduction of lipoxin A4, but an increase in the synthesis of leukotrienes.Supporting our previous data, we observed that formyl peptide receptor, a receptor that recognizesSPMs, was 30% decreased in arteries from in SHR. Together, these data show that vascular tissuepresents with the “machinery” to synthesize SPMs, and the resolution of inflammation“machinery” is impaired in hypertension.
Abstract P140: Indanyloxyacetic Acid-94 Decreases Contraction In Uterine Arteries In Response To Phenylephrine And Decreases Response To Phenylephrine After Ca
2+
Replacement
Authors: Wilczynski Stephanie , Arishe Olufunke , Priviero Fernanda , Webb R. Clinton
Published: September 2022

Background:
Chloride Intracellular Channels (CLICs) are a family of transmembrane proteins that can be present on the plasma membrane or the membranes of a number of organelles. These channels are redox and pH sensitive and present a unique target to understanding the vascular response to reactive oxygen species (ROS). By regulating oxidative stress, these channels may play a role in the pathology of vascular dysfunction. Uterine arteries were chosen as the focus of this project because of the lack of research involving its vascular function and role in disease.

Hypothesis:
This project hypothesizes that IAA94 will decrease vasoconstriction in response phenylephrine and enhance the relaxation response to acetylcholine in an endothelial-dependent manner.

Methods:
Vascular reactivity tests on wire myographs were performed in endothelium intact (E+) and denuded (E-) uterine arteries from Wistar rats. Rings were kept in Krebs solution at 37°C and constantly aerated with 95%O
2
/5%CO
2
. Concentration-response curves to phenylephrine (PE; 10
-9
-3x10
-5
M), and acetylcholine (ACH; 10
-9
- 3x10
-5
M) were performed in the absence or in the presence of IAA94 (50 uM). Vascular reactivity to 3*10
-6
M PE was also performed in Ca
2+
free Krebs solution with washout of intracellular Ca
2+
and replenishing of external Ca
2+
. A concentration response curve was completed to potassium chloride (KCL; 1mM - 100mM). Concentration-response curves were analyzed using non-linear regression analysis. Data are presented as mean ± S.E.M. Statistical significance set at p<0.05. Data analyzed with GraphPad Prism 9.2.0.

Results:
In the E+ rings, IAA -94 inhibited contractile response to PE (pEC
50
: control 6.684 ± 0.1433 vs. IAA94 treated 5.616 ± 0.89, p<0.0001). The E- had decreased inhibitory effects of IAA-94 on contractile response to PE (pEC
50
: control 5.832 ± 0.19 vs. IAA94 treated 5.32 ± 0.21, p= 0.2034). IAA94 treatment did not significantly change the contraction to KCL, while the IAA94 treatment did significantly decrease the rings response to PE after Ca
2+
washout and replenishment.

Conclusion:
The data show that IAA94 decreases the contractile response to PE in an endothelial dependent manner that is separate from the K
+
flux from KCL-induced contraction.
Abstract P200: Long-term Cardiovascular Risk In Hypertensive Emergencies Or Urgencies
Authors: Elliott William J
Published: September 2022

Hypertensive emergencies (severely elevated blood pressure with evidence of acute, ongoing target-organ damage) are traditionally distinguished from “hypertensive urgencies” (if they really exist) by the need for prompt, but controlled, reduction in blood pressure in the former. The longer-term cardiovascular risk associated with these conditions has not been well characterized. A systematic review of the literature was therefore conducted, which identified 6 reports about subsequent death or cardiovascular hospitalization after successful treatment for either diagnosis (
J Hypertens
. 2008;
26:
657;
J Clin Hypertens
. 2011;
13:
551;
JAMA Intern Med
. 2016;
176:
981;
J Clin Hypertens
. 2017;
19:
137;
J Hypertens
. 2021;
39:
2514; and
Eur J Prev Cardiol
. 2022;
29:
194). The pooled average annualized risk of death or cardiovascular hospitalization for patients with hypertensive emergencies was 26±8% (168 of 640, 4 reports); compared to 4±1% (76 of 2041, 5 reports) for hypertensive urgencies. Rates of the same outcome were 11±2% (8 of 70) among subjects randomized to placebo in the original Veterans Administration trial (
JAMA
. 1967;
202:
1028), and 3±1% (182 of 6110 in two fairly recent trials in patients with less severe, but “high-risk” hypertension (LIFE:
Lancet
. 2002;
359:
995, VALUE:
Lancet
. 2004;
363:
2022). Despite moderate heterogeneity within the diagnostic groups, these data highlight the very high residual cardiovascular risk of people with successfully-treated hypertensive emergencies, compared to untreated Veterans with diastolic blood pressures between 115-129 mm Hg, both of which are much higher than people with hypertensive urgencies, or patients with hypertension and other cardiovascular risk factors.
Abstract P205: A Novel Wearable Monitor Shows Diurnal Changes Of Multiple Hemodynamic Parameters In Ambulatory Individuals
Authors: Eisenkraft Arik
Published: September 2022

Introduction:
Recent technological developments enable noninvasive monitoring of hemodynamic parameters, improving big data-driven insights on diurnal changes. We assessed the hypothesis that a novel medical grade wearable monitor could depict trends of multiple cardiovascular parameters in ambulatory individuals.

Methods:
Physiological parameters were monitored for 24 hours in ambulatory volunteers using a photoplethysmography-based wearable monitor. These included stroke volume (SV), cardiac index (CI), systemic vascular resistance (SVR), blood oxygen saturation (SpO
2
), respiratory rate (RR), systolic (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and heart rate (HR). Diurnal variations were evaluated among all participants, and analyses were stratified based on sex, age, and body-mass index (BMI).

Results:
A total of 256 participants were included in the analysis. All measured parameters showed significant (p<0.001) diurnal changes. Nighttime values were lower excluding RR and SVR, reaching the nadir at 5 am, and then increasing to a maximum at 10 am, plateauing, and gradually declining from 7-8 pm. CI demonstrated a reduction of 0.6 L/min/m
2
(20%), while SVR demonstrated the opposite trend and was higher during the night increasing by up to 212 dynes/sec/cm
–5
(16%). Females demonstrated higher HR and CI with lower SVR during daytime and nighttime. Obese participants (BMI>30 kg/m
2
) had a higher SBP and DBP, and lower SV and CI. SVR was higher among the elderly.

Conclusions:
In conclusion, diurnal changes corresponding with awake-sleep hours were noticed and differed between sex, age, and BMI groups. This suggests that wearable monitoring platforms could shed more light on hemodynamic changes in subgroups, and might help with future efforts to provide tailored personalized medicine and pre-symptomatic diagnosis and prevention.
Abstract P209: Ambulatory Arterial Stiffness Index In Detecting Autonomic Failure
Authors: Khan Ghazi , Giacona John , Wang Jijia , Pittman Danielle , Vongpatanasin Wanpen
Published: September 2022

Previous studies have shown standard deviation (SD) of daytime ambulatory systolic BP (DaySBP) as a screening tool for detecting autonomic failure. While ambulatory arterial stiffness index (AASI) has shown to be a predictor of cardiovascular morbidity and mortality, the usefulness of AASI in detecting the presence of autonomic failure has not been investigated.

We assessed AASI in 336 hypertensive and normotensive adults with and without autonomic failure (ATF). Area under receiver operator characteristic curve (AUROC) was calculated to determine accuracy of AASI in detecting ATF. Bayes factor (BF) was used to assess the significance of the difference between AUROC of AASI compared to SD daytime SBP and AASI combined with SD daytime SBP compared to SD daytime SBP alone. Sensitivity and specificity of AASI in detecting autonomic failure was derived using cut-off points from Youden’s Index.

Prevalence of ATF in our cohort was 14 % (47/336). The prevalence of HTN was 55 % (184/336). The mean age of the ATF group was higher than the control group (71 ± 11 vs. 61 ± 14 years, respectively, p < 0.05). The mean AASI of ATF patients was higher than control group (0.58 ± 0.11 vs. 0.51 ± 0.15, respectively, p < 0.05). The AUROC of AASI in ATF detection was not significantly higher than SD daytime SBP (BF =0.12). Sensitivity and specificity of AASI was 87 % and 43 %, respectively. The optimal cutoff for AASI selected by Youden’s index was 0.48. The addition of AASI to SD daytime SBP significantly improved ATF detection compared to AASI alone (BF > 3, Fig 1).

In conclusion, AASI in combination with SD DaySBP significantly outperformed AASI alone in detecting autonomic failure in patients with or without HTN.
Abstract P218: Risk Factors Of Dementia In Patients With Hypertension: A Population-Based Cohort Study
Authors: Jung Mi-Hyang , An Sang Joon , Sung KiChul
Published: September 2022

Background:
Patients with hypertension are at higher risk for dementia than the general population. We sought to understand the relative importance of various risk factors in developing dementia among hypertensive patients.

Methods:
This population-based cohort study used the database from the Korean National Insurance Service. Eligible individuals were 40-79 years adults with hypertension and without previous history of stroke or dementia at 2007-2009. To test the relative importance of risk factors on the development of dementia, R
2
values for each potential risk factor were calculated from the Cox proportional hazard model.

Results:
Overall, 650,476 individuals (mean age 60 ± 11) with hypertension were included in the analyses. During a mean 9.5 years of follow-up, 57,112 cases of dementia were observed. The top 3 strongest predictors for dementia were age, comorbidity (assessed by Charlson Comorbidity Index), and sex. The next strongest risk factors were physical activity, followed by smoking, alcohol consumption, body mass index, use of statin, fasting glucose level, blood pressure control status, and hypertension duration.

Conclusions and Relevance:
Controlling comorbidity is of utmost importance to prevent dementia in patients with hypertension. Together with this, we should put more effort into encouraging physical activity, smoking cessation, and moderation of alcohol for primary prevention of dementia.
Abstract P224: Perivascular Adipose Tissue May Contribute To Disparate Blood Pressure Responses To Lifetime High Fat Feeding In Dahl Salt-sensitive And Salt-resistant Rats
Authors: Fink Gregory , Garver Hannah , Hix Jeremy , Krieger-Burke Teresa , Watts Stephanie W
Published: September 2022

Dahl salt-sensitive (SS) and salt-resistant (SR) rats show dramatically different blood pressure (BP) responses to being raised on a high fat, but normal salt, diet starting at weaning. Virtually no effect on BP is seen in SR rats, whereas in SS rats mean arterial pressure (MAP) reaches over 160 mmHg by adulthood. The BP difference is similar in female and male rats. The cellular and physiological mechanisms responsible have not been completely elucidated in either sex. Dysfunctional perivascular adipose tissue (PVAT) is proposed to contribute to obesity-associated hypertension through actions on other components of the vascular wall. Here we used female rats to test the hypothesis that differences in adipose tissue amount or function in SS and SR rats play a part in the distinct BP effects of high fat diet in the two strains. Rats (n=8 per strain) were fed a high fat diet (60% kcal fat) from weaning. BP was measured with telemetry. At 18 weeks of age, MAPs (mmHg) were 108±1 and 180±4 in SR and SS rats. Body weights (g) were 274±4 and 323±4. Total and visceral adipose volumes (mm3) measured by μCT were higher in SS rats versus SR rats (visceral: 22372±927 versus 14112±1495; total: 17208±732 versus 10234±984). PVAT volume around the thoracic aorta was larger in SS rats (0.228±0.017 versus 0.167±0.006). Subcutaneous adipose tissue volumes did not differ. Plasma triglycerides and cholesterol were modestly but significantly higher in SS rats. The well-known anticontractile effect of PVAT was compared in thoracic aorta from both strains. Removal of PVAT increased the AUC of the tension/PE contraction in SR rats by 1484±226 units and by a significantly smaller amount (946±162.5 units) in SS rats. Finally, aortic stiffness was estimated from pulse wave velocity measured via Doppler in a subset (n=4 each) of rats from each strain. Pulse wave velocity (M/sec) was markedly higher in SS than SR rats (11.5±1.0 versus 6.4±0.3). We conclude that differences in adipose tissue volume, location or function could account in part for the distinct BP responses of female SS and SR rats to high fat feeding.
Abstract P228: HYPERTENSIVE ARTERIAL STIFFNESS LEADS TO BAROREFLEX DYSFUNCTION
Authors: Duarte Mariano , Aquieri Analía , Coyle Javier , Yaryour Claudio , Reyes Toso Carlos
Published: September 2022

Introduction:
The rapid regulation of blood pressure allows the continuous adaptation of the cardiovascular system. It is carried out by baroreflex (BR). Despite the hypertensive (HT) damage to the arterial wall and BR structures are located within it, the impact of hypertension (HYP) on the BR function has not been fully studied. We hypothesized that HYP has decreased BR function caused by increased arterial stiffness (AS).

Mat. and Methods:
In prospective study, 101 patients over 65 years of age were included; G1: HT G2: Normotensive (NT). BR function: A continuous rhythm strip in lead DII of electrocardiogram and the Valsalva maneuver was performed. Chronotropic response at the end of the test was established by the lowest R-R recorded up to 5 beats post-Valsalva. According with AHA, BR function was established by the greatest variation in heart rate (smallest R-R) within 5 immediate beats over Valsalva. Results 2 populations: A-BR Nomofunction: increase 10 and 30 beats. B-BR hypofunction, increase < 10 beats. Assessment of AS by means of pulse wave velocity (PWV) by Complior System device, the "gold standard" for the non-invasive measurement.

Results:
101 patients (43 men) were studied, 76 of them were HT (147.2 ± 15.7 mmHg) and the rest NT (130.2 ± 10.8 mmHg) p<0.05. BR hypofunction was observed in 60 of the 76 HT and only in 3 of the 25 NT. PWV was higher in the HT vs. NT (10.54 vs 8.58 m/s) p<0.001

Conclusions:
As hypothesized, 8/10 in G1 had decreased BR function and only 1/10 in G2. Best predictors of BR hypofunction were sought by multivariate analysis were HYP and AS. So, AS could be one of the causal links between HYP and BR hypofunction and would explain the HT baroreceptor desensitization.
Abstract P232: Endothelin B Receptor Modulation Of Diurnal Blood Pressure Amplitude During High Salt Diet
Authors: Becker Bryan , Pollock David M
Published: September 2022

High salt diet can alter baroreflex sensitivity. We have previously shown that rats deficient in endothelin B receptors (ET
B
-R) demonstrate an exaggerated diurnal blood pressure amplitude similar to that seen in rats with sinoaortic denervation fed a high salt diet. However, it remains unclear if ET
B
-R influence on baroreflex function is due to sensory or efferent mechanisms of autonomic blood pressure control. We employed selective ET
B
-R antagonism using A192621 in ET
B
-R deficient rats (ET
B
-def) that only express functional ET
B
-R on efferent nerves and transgenic controls (TG) to isolate the role of efferent vs sensory pathways. Rats with telemetry were fed a normal salt diet (0.49% NaCl) during baseline and osmotic minipump infusion of 10 mg/kg/day A192621 or vehicle. After one week of infusion, animals were fed a high salt (4.0% NaCl) diet. Selective ET
B
-R blockade increased 24 hr MAP in TG animals during normal salt diet (+16.4 ± 1.0 mmHg from baseline; n = 10; p < 0.001) but had no effect on ET
B
-def (-1.2 ± 1.8 mmHg; n = 7; p > 0.99 ). A192621 treated TG rats did not exhibit a further increase in pressure following high salt diet (+5.5 ± 1.3 mmHg; n = 6; p = 0.25), but both vehicle and A192621 treated ET
B
-def rats displayed a salt-sensitive increase in MAP (+15.9 ± 4.2 and +14.4 ± 4.5 mmHg; n = 3 and 4; p = 0.003 and 0.001, respectively). A192621 treatment had no significant effect on MAP amplitude (light-dark difference) in any group during normal salt diet. However, during high salt, A192621 treated TG animals had an increase in MAP amplitude (+9.7 ± 0.7 mmHg; n = 6; p = 0.002), and vehicle had no effect (+0.8 ± 0.8 mmHg; n = 5; p = 0.97). Both A192621 and vehicle treated ET
B
-def rats had a similar increase in amplitude following high salt diet (+9.3 ± 0.6 and +8.6 ± 1.4; n = 4 and 3; p = 0.001 and 0.018, respectively). In summary, antagonism of ET
B
-R increased MAP only in TG rats but did not have an effect on diurnal amplitude during normal salt in any group. Antagonism of ET
B
-R during high salt diet caused TG rats to exhibit a similarly high diurnal amplitude as ET
B
-def rats. These data suggest that blocking ET
B
-R on baroreflex sensory pathways are the mitigating cause for increased diurnal blood pressure rhythms during high salt diet.
Abstract P234: Arterial Hypertension, Insulin Resistance And Depressive-like Behavior In
Crtc1
-deficient Mice
Authors: Morhenn Karoline , Seniuk Anika , Ehmke Heimo
Published: September 2022

Background:
Epidemiological evidence has demonstrated a link between cardiovascular disease, metabolic syndrome and depression. Whether this association is causal and what mechanisms may be involved is still unknown. Studies in humans and mice suggest that alterations of the CREB-BDNF pathway can contribute to the development of both, eating disorders and major depressive disorders. Mice deficient in the CREB-regulated transcriptional coactivator 1 (Crtc1) have been shown to become overweight and display depressive-like behavior. Here, we investigated whether
Crtc1
-deficient mice concomitantly exhibit a hypertensive, insulin resistant and depression-like phenotype.

Methods:
Mean arterial blood pressure and heart rate were measured by radiotelemetry in unrestrained
Crtc1
-deficient mice (KO) and wildtype littermates (WT). Renal renin expression was quantified by qPCR. Insulin resistance was determined by the i.p. glucose tolerance test, and depressive-like behavior was assessed by the soiled bedding preference test.

Results:
Crtc1
-deficient mice had higher arterial blood pressures (dark: KO 117±2 mm Hg, WT 107±2 mm Hg, p<0.05; light: KO 102±2 mm Hg, WT 94±2 mm Hg, p<0.05, 1-way ANOVA, n=8-11) and heart rates (dark: KO 593±11 bpm, WT 596±7 bpm; light: KO 529±12 bpm, WT 494±8 bpm, p<0.05, 1-way ANOVA, n=8-11). Relative renin mRNA expression was not different between genotypes (KO 0.86±0.07, WT 1.00±0.10, n=10). Glucose tolerance was significantly impaired in
Crtc1
-deficient mice (maximum plasma glucose concentrations KO 423±27 mg/dl, WT 295±27 mg/dl, p<0.0001, 2-way ANOVA, n=9). In the soiled bedding preference test, male
Crtc1
-deficient mice exhibited a lack of preference for female-soiled bedding over clean bedding (female vs. clean KO 75.3±11.2 s vs 79.0±11.0 s, WT 119.5±13.5 s vs. 51.5±10.5 s, n=2-3).

Conclusions:
Crtc1 might be a molecular component of a pathway that connects arterial hypertension, metabolic syndrome and depression.