bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 130: Impact Of O-GlcNAcylation On Elastin Fragmentation In Aorta Of Aged Male And Female Fisher344 Rats
Authors: Januario Da Costa Tiago , Montandon Ian , Wilson Emily , Tavares Milene , Pernomian Laena , McQuail Joseph , Webb R Clinton C , Wenceslau Camilla F , McCarthy Cam
Published: October 2023

O-GlcNAcylation is a regulatory mechanism involving the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins, playing a crucial role in cellular processes. Within vascular smooth muscle cells (VSMCs), O-GlcNAc impacts vascular function and is associated with cardiovascular risk. Vascular aging is characterized by changes in VSMCs, such as stiffness and loss of elasticity. Elastin, a component of the extracellular matrix, undergoes fragmentation during aging, triggering detrimental cascades and damage to end-organs. This study explores the correlation between O-GlcNAc and elastin fragmentation as a hallmark of aging. Specifically, we hypothesized that higher levels of O-GlcNAc induces fragmentation. Male and female Fisher 344 rats were evaluated at 3-(3M) and 16-month-old (16M). Thoracic aortas were isolated and strain/stress was measured with a tissue puller (DMT
®
), and systolic blood pressure (SBP) was measured in the carotid artery. O-GlcNAc levels, elastase expression and activity, and elastin fragmentation were assessed using Western blot, immunofluorescence, and histology. Data were analyzed using Two-way ANOVA-Tukey post-hoc (p<0.05). Results showed an age-related increase in blood pressure with the SBP in 16M males ~30 mmHg higher than in 3M (87±3 vs. 117±4). In females, there was a modest increase of about 16 mmHg in 16M than 3M (83±4 vs. 99±4). Aortic thickness increased in 16M male (3M 99±4 vs. 16M 114±3) and female (3M 99±3 vs. 16M 123±3) compared to 3M, but no sex difference was observed. The number of fragmented elastin fibers/cm of aorta was higher in 16M females (7±3) than 3M (2±1) and the elastase activity is 40% higher in aorta and serum of 16M females.Functionally, the aorta of 3M male rats, but not 16 M, exhibited higher strain/stress than age-matched females (3M male 2.5±0.9 vs. female 1.6±0.6; 16M male 5.1±0.9 vs. female 4.6±0.6). Interestingly, aged females and males presented higher levels of O-GlcNAc, and pharmacological induction of O-GlcNAc using Thiamet G (1uM) increased aortic stiffness and elastin fragmentation in 3M male rats (2.1±0.9 vs. 3.6±0.9). These findings suggest that O-GlcNAc contribute to aortic stiffness and blood pressure during aging, possibly through inducing elastin fragmentation.
Abstract 131: Phosphoproteomics Analysis Reveals That Angiotensin-(1-5) Inhibits MTOR Signalling Pathway In Endothelial Cells
Authors: Souza-Silva Igor M , Peluso Augusto , Ribeiro Lucas , Rodrigues Andre , Jakobsen Lene , Jensen Pia , Sumners Colin , Bader Michael , Larsen Martin , Verano-Braga Thiago , Steckelings Ulrike Muscha M
Published: October 2023

Introduction:
Our group demonstrated that Angiotensin-(1-5) [Ang-(1-5)] is a biologically active component of the protective arm of the Renin-Angiotensin System (RAS), displaying high efficacy towards the AT
2
R. However, signaling mechanisms for Ang-(1-5)
in vitro
are still unknown.

Objective:
To characterize Ang-(1-5) signaling signature in human aortic endothelial cells.

Methods:
Human aortic endothelial cells (HAEC) were stimulated with Ang-(1-5) (1μM) for 1, 3, 5 or 20 minutes. Proteins were isolated, digested and labeled with TMTpro
TM
16-plex. Phosphorylation changes of proteins in response to Ang-(1-5) treatment were analyzed by mass spectrometry. Raw data were processed in Proteome Discoverer. General bioinformatic analysis was performed in R Studios and functional analysis was performed with DAVID and Cytoscape. Validation of phosphoproteomics data was performed by western blot in HAEC treated with Ang-(1-5) (1μM) for 1, 3, 5 or 20 minutes.

Results:
Treatment of HAEC with Ang-(1-5) significantly modified the phosphorylation status of 831 proteins at 1799 residues, majority of these being dephosphorylated (1079). Functional bioinformatic analysis revealed a cluster of proteins involved in cell cycle and cell division regulation. Upon further analysis, we observed that Ang-(1-5) led to dephosphorylation of residues of CLIP-170 (Ser
195
, Ser
200
, Ser
204
), 4EBP1 (Ser
65
), S6K1 (Ser
447
) and ribosomal S6 protein (Ser
244
, Ser
247
), suggesting an inhibitory effect on mTOR activity. Western blot analysis confirmed the inhibitory effect of Ang-(1-5) on mTOR signaling, as a significant dephosphorylation of Ser
65
-4EBP1 [% vs. CT = 69.9%] and Thr
389
-S6K1 [% vs. CT = 43.7%] was observed at all timepoints tested. These effects were AT
2
R-mediated, since PD123319 prevented dephosphorylation of Ser
65
-4EBP1 and Thr
389
-S6K1 driven by Ang-(1-5).

Conclusion:
This study provides an in-depth analysis of Ang-(1-5) signaling patterns in HAEC. The overall similarity of Ang-(1-5) and C21 intracellular signaling further supports that Ang-(1-5) is a hormone of the protective RAS. Since inhibition of mTOR in endothelial cells is known as an anti-senescence mechanism, further investigations are needed to confirm an anti-senescence effect of Ang-(1-5).
Abstract 140: Implementation Of The World Health Organization Hearts Package Lowers Blood Pressure And Improves Hypertension Control In Rural Bangladesh: A Quasi Experimental Trial
Authors: Abrar Ahmad , Akhtar Jubaida , Hu Xiao , Jubayer Shamim , Nabi Sayem Mohammad Noor , Sultana Sarmin , Al Mamun Mohammad Abdullah , Bhuiyan Mahfuzur Rahman , Malik Fazila-tun-nesa , Amin Mohammad Robed , Alim Abdul , Gupta Reena , Zhao Di , Farrell Margaret , Matsushita Kuni , Burka Daniel , Appel Lawrence J , Moran Andrew E , Reza Choudhury Sohel
Published: October 2023

Background:
The World Health Organization (WHO) promotes the HEARTS technical package for improving hypertension control worldwide, but its effectiveness has not been evaluated.

Methods:
We conducted a quasi-experimental trial in primary healthcare facilities, Upazila Health Complexes (UHC), in rural Bangladesh. We enrolled a total of 3935 patients (mean age 52.3y, 70.5% female) with uncontrolled hypertension (blood pressure [BP] ≥140/90 mmHg): 1950 patients from 7 UHCs implementing HEARTS and 1985 patients from 7 matched usual care UHCs. The HEARTS package intervention components were 1) simplified treatment protocol, 2) reliable medication supply, 3) team-based care, 4) standardized follow-up, and 5) a mobile app to record BPs and medications. The primary outcome was systolic BP at 6 months measured at the patients' home; secondary outcomes were diastolic BP, hypertension control rate (<140/90 mmHg), and loss to follow-up. We ran multivariable mixed-effect linear and Poisson models.

Results:
At baseline, mean systolic BP was 158.4 mmHg in the intervention arm and 158.8 mmHg in the usual care arm. Follow-up was 95.5%. Compared to usual care, the intervention significantly lowered systolic and diastolic BP (Figure) and improved BP control (62.0% vs. 49.7%, p<0.001). Loss-to-follow-up was lower in the intervention arm (8.8% vs. 39.3%, p<0.001).

Conclusions:
The WHO HEARTS package implemented in rural Bangladesh significantly lowered BP and improved hypertension control. These results support use of the WHO HEARTS package to control hypertension in Bangladesh and provide a strong rationale for its implementation in other low and middle-income countries.
Abstract P101: Clinical Risk Prediction Scores For Primary Aldosteronism
Authors: Settelmyer Zachary , Buhnerkempe Michael , Prakash Vivek , Botchway Albert , Roy Stephen , King Kristin , Adekola Oritsegbubemi , Cheema Asad , Williams Vanessa , Jakoby Michael , Flack John M
Published: October 2023

Introduction:
Primary aldosteronism (PA) is a common and often underdiagnosed secondary cause of hypertension with cardiovascular, kidney, and metabolic disease rates far in excess of essential hypertension matched for blood pressure levels. Current clinical scoring algorithms could reduce patient and healthcare burdens associated with expanded PA screening but have not been extensively validated in external cohorts.

Methods:
We evaluated six PA scoring algorithms in two populations of patients seen in the Southern Illinois University (SIU) Hypertension clinic: all patients screened for PA where a negative screen was assumed to rule out PA without further testing (n = 592) and only screen positive patients with subsequent confirmatory testing (n = 90). Area under the receiver operating characteristic curve (AUC) was used to determine their overall performance predicting PA. Negative predictive value (NPV) was used to assess the ability to identify patients with a low probability of PA.

Results:
Only one score showed an acceptable ability to predict PA (AUC > 0.7). NPV was inflated in the all screen cohort compared to confirmatory testing, where known status yielded low NPV for all scores.

Conclusion:
Currently available scoring algorithms poorly predict those with PA under current diagnostic guidelines. Equating a negative screen with a negative confirmatory test, as was common in score development, artificially inflates the NPV of these scores. Scores show limited utility in identifying screen positives that do not need to undergo further evaluation. More accurate PA risk prediction scores are needed to guide decision-making in patients suspected of having PA.
Abstract P104: EXAMINING THE EFFECTS OF FOLLISTATIN ON CONTRACTION OF VESSELS FROM NORMOTENSIVE AND HYPERTENSIVE RATS
Authors: Sadat Afjeh Niki , Kuganathan Ann , Leal Marcos , Lu Vincent , Dickhout Jeffrey , Krepinsky Joan
Published: October 2023

The lab has previously shown that follistatin (FST), a glycoprotein inhibitor of activins, reduced blood pressure in the Spontaneously Hypertensive Rat (SHR) model of Essential Hypertension. Short-term exposure (30 minutes) to FST also reduced vessel contraction induced by potassium (KCl). This study aims to illustrate the mechanisms through which FST inhibits potassium-induced contraction in SHR and normotensive (WKY) rats. Function of SHR or WKY resistance mesenteric arteries was tested in response to KCl and ion channel modulators using wire myography. Cultures of primary smooth muscle cells (SMC) were also established from these vessels using cell explant technique. The calcium sensor dye Fluo-4 AM was used to examine calcium influx on a cellular level. To test whether FST effects were due to activin neutralization or activin-receptor inhibition, neutralizing antibodies against activin A and B or an activin receptor inhibitor (SB 431542) were used, respectively. Only activin A neutralization in the SHR reduced KCl-induced contraction similarly to FST. Activin receptor inhibition also reduced KCl constriction similarly to FST. When directly stimulated with Activin A, both WKY and SHR vessels displayed augmented KCl contraction compared to controls but the effect was more pronounced in the SHR. Preliminary Fluo-4 results showed that FST decreased KCl-induced calcium influx in SMC. Since activin A was shown to increase L-type voltage-gated Ca2+channel activity, an agonist (FPL 64176) of this channel was used to induce contraction. Although FST reduced KCl-induced contraction, it did not affect FPL-induced contraction in either SHR or WKY. Thus, Activin A neutralization reproduces FST reduction of KCl-induced vessel contraction. FST did not reduce FPL-induced contraction, suggesting that its inhibition of KCl-induced contraction is not through effects on this channel but rather an alternate Ca2+ or K-ATP channel.
Abstract P105: High-throughput Sequence Symmetry Analysis To Detect Angiotensin-converting Enzyme Inhibitors (acei) Induced Prescribing Cascades.
Authors: Smith Kayla , Morris Earl , Ndai Asinamai , Keshwani Shailina , Kulkarni Priyanka , Schmidt Stephan , Pepine Carl , Vouri Scott , Smith Steven M
Published: October 2023

Introduction:
ACEIs are the most commonly prescribed antiHTN drugs, but side effects may prompt additional therapy resulting in a prescribing cascade. We aimed to identify potential ACEI-induced prescribing cascades using high throughput sequence symmetry analysis.

Methods:
Using claims from 5% (2011-15) and 15% (2016-20) national samples of Medicare FFS beneficiaries, we identified new ACEI users aged ≥66 y with continuous enrollment for ≥360 days pre- and ≥180 days post-ACEI initiation. We screened for initiation of 446 other ‘marker’ drug classes (based on WHO Anatomical Therapeutic Classification level 4 codes) within ±90 days of ACE initiation, generating sequence ratios (SRs) representing the proportions of ACEI initiators starting the marker class after, vs before, the ACEI. Adjusted SRs (aSRs), accounting for prescribing trends over time, were calculated with 95% CIs >1 considered statistically significant.

Results:
We identified 297,410 ACEI initiators (mean ± SD age, 76.1 ± 7.5 y; 59% women, 88% HTN). Of 446 ‘marker’ classes studied, and excluding other antiHTN classes, we identified 110 statistically significant signals indicative of potential prescribing cascades. The 30 strongest prescribing cascade signals (by aSR) are summarized (Figure) and included decongestant nasal preparations and monoamine oxidase B inhibitors.

Conclusion:
We identified potential prescribing cascade signals reflecting known and possibly underrecognized ACEI adverse events in this Medicare cohort. Additional research is needed to determine impact of these cascades on patient outcomes.
Abstract P111: Comparison Of Automated Office Blood Pressure And Self-Measured Blood Pressure: Results From An Ongoing Self-Measured Blood Pressure Program
Authors: Farahmand Rosemary , Cluett Jennifer L , Barkowski Laken , Cohen Marc L , Li Jonathan X , Olowoyeye Ruth , Padwal Raj , Rakotz Michael K , Russo Elisabeth , Sachdev Neha , Tighe Katherine M , Tsipas Stavros , Walley Hannah , Wood Peter S , Wozniak Gregory , Juraschek Stephen P
Published: October 2023

Background:
HTN treatment based on AOBP lowers risk of CVD. SMBP has been promoted as an alternative to AOBP that could improve access and achieve more timely BP control. However, questions remain about the concordance between SMBP and AOBP.

Objective:
To compare SMBP and AOBP measurements in a 6-month SMBP program.

Methods:
In this quality improvement study, we examined data from an ongoing SMBP pilot program in a large general medicine practice in Boston. Referred patients underwent AOBP during an initialization clinic visit and then performed SMBP for a week each month over a 6 month period. During the 6
th
month of the program, patients performed a final week of SMBP and returned to clinic for an AOBP assessment. We compared the 6
th
month mean BPs via paired t-tests.

Results:
Of 129 patients referred, 74 underwent an initialization visit and at least 1 month of monitoring (mean age 59±13, 53% female, 28% Black). The mean referral BP was 140±11/84±11 mm Hg. In contrast, during program initialization, mean AOBP was 131±13/79±10 (difference compared to referral BP was -9/-5 mm Hg;
P
<0.001 for both). The mean BP measured the month after initialization using the 1-week SMBP protocol was 133±12/83±7 (difference compared to AOBP was +2/+4;
P
=0.18 for SBP;
P
<0.001 for DBP). For the 12 patients that completed 6-months thus far, mean AOBP at the 6-month visit was 127±10/76±8. The mean BP the week of SMBP during the 6
th
month of the program was 124±9/79±5 (difference compared to 6-month AOBP was -3/+2 mm Hg;
P
>0.05 for both) (
Figure
).

Conclusion:
BP measures from SMBP tracked well with in-office AOBP measurements. These findings add to existing evidence that SMBP might be used in lieu of AOBP for HTN management.
Abstract P115: Cost-related Medication Non-adherence Among Non-elderly Hypertensive Adults In The United States.
Authors: Aryal Anu , Rasmussen Petra , Moucheraud Corrina
Published: October 2023

Background:
In the US, approximately 20% of prescriptions are never filled, and 50% of filled prescriptions are non-compliant with provider’s recommendations. The affordability of prescribed medicines could be a barrier for hypertensive patients leading to cost-related medication non-adherence (CRN).

Methods:
We used the National Health Interview Survey 2019 adult dataset to study predictors of CRN among non-elderly hypertensive adults aged 18-64. We defined CRN dichotomously based on four yes or no questions: delayed, skipped, took less medicine, and didn’t get medicine due to cost or to save money. We report descriptive statistics for the entire sample (n=5695) and a multivariable logistic regression model for the lower-income sub-sample with ≤138 federal poverty levels (FPL) (n=845).

Results:
Around 16% of respondents reported CRN. Females experienced CRN at a higher proportion (19.9%) than men (12.7%). Those uninsured, below 200% of the FPL, with less than a high school education, unemployed last week, had additional co-morbidities, and identified as non-Hispanic Black, more commonly experienced CRN compared to their counterparts. The subgroup analysis among lower-income (≤138 FPL) revealed an even higher rate of CRN (25.1%). Gender-based differences still existed in this sub-group, with higher CRN among women (27.6%) than men (22.5%). However, in the regression model with gender, insurance, age, education, race, co-morbidity, rural/urban geography, and having a usual source of care as covariates, only co-morbidities and insurance status had statistically significant associations. Those with one additional co-morbidity had 1.98 times the odds, and those with four or more additional co-morbidities had 3.88 times the odds of CRN compared to those with hypertension only. Medicaid enrollees had significantly lower odds of reporting CRN (OR = 0.28, p-value <0.001) than those uninsured.

Conclusion:
Our study provides evidence of an overall high prevalence (16%) of cost-related medication adherence in non-elderly hypertensive Americans and an even higher rate (25%) among those with lower income. As non-adherence to medication could lead to poor hypertension control, removing financial barriers to access medicines is imperative.
Abstract P119: Patients With Arterial Hypertension And Hypertrophic Cardiomyopathy Affected By Pulmonary Hypertension Have Worse Clinical Outcomes, Nation-wide Study
Authors: KHOKHLOV LEONID R , Rahima Kenan , Eshghabadi Amin , Mateo-Faxas Sila , Hijazi Mohamad , Hussain Fatima , Ali Mehnaaz , Mena Angel , Shemisa Kamal
Published: October 2023

Background:
HCM is a predominantly genetic disorder affecting the cardiac muscle and its functionality. PH is a known predictor of adverse outcomes. There is limited evidence of clinical outcomes in HCM population with HTN (as a surrogate for preserved contractility) affected by PH.

Methods:
We queried NIS between 2017-2020 for adult patients with HCM&HTN who had PH. The primary outcome was mortality. The secondary outcomes were cardiogenic shock, cardiac arrest, intubation, length of stay (LOS) and total hospital cost. Multivariable logistic and Poisson regression analyses were used to estimate outcomes.

Results:
There were 35,640 hospitalizations with HCM&HTN, of which 1950 (5.4%) had PH. PH and non-PH cohorts were with mean age of 71.6 vs. 65.2 yrs; males 35.2% vs 48.6%; Caucasians 67.3% vs 65.9%; HF 16.8% vs 4.1%; sHF 2.8% vs 0.9%; dHF 13.2% vs 2.8%; ACS 14.2% vs 13.6%; STEMI 1% vs 0.8%; obesity 22.7% vs 21.1%; anemia 18.8% vs 12.7%; AF 52.8% vs 32%; CKD 4% vs 1.4%; history of MI 10.2% vs 9.3%; COPD 29.8% vs 15.7%, respectively. PH cohort had significantly worse clinical outcomes and resource utilization (Table 1).

Conclusion:
HCM patients with HTN and co-existent PH had significantly higher rates of cardiogenic shock and higher resource utilization. There is a tendency to higher mortality in cohort with PH. This cohort was older, white females with more prevalent HF (systolic and diastolic), ACS, anemia, AF, obesity, CKD, past MI, COPD. PH is associated with increased rates of heart failure, cardiac arrhythmias, pulmonary and renal diseases. Detection and appropriate management of PH in patients with cardiomyopathies may have clinical benefit and play a role in prognostication.
Abstract P120: Effect Of Alamandine On Isoproterenol-induced Left Ventricular Dysfunction, Cardiac Remodeling And Immune Responses In Rat
Authors: Md Irfan Nafis , Yu Yang , Chen Qing , Wei Shunguang
Published: October 2023

Alamandine, a newly identified derivative of angiotensin II has been shown to exert antihypertensive and vasodilative actions, and may represent a novel component of cardioprotective axis of renin angiotensin system. We sought to determine the protective effects of alamandine on isoproterenol (ISO) induced cardiac remodeling and dysfunction in rats. Male SD rats (n=6 in each group) received a two-week subcutaneous infusion of vehicle, ISO (10 mg/kg/day) or a combination of ISO and alamandine (50 ng/kg/min). Compared with vehicle group, the ratio of heart/body weight (mg/g) in ISO treated rats was significantly (*P<0.05) elevated (3.93 ± 0.18 vs. 3.07 ± 0.08*), which was markedly attenuated by alamandine (3.50 ± 0.08*). Echocardiographic assessment showed that alamandine improved ISO-induced left ventricular (LV) dysfunction evidenced by reducing LV thickness (1.68 ± 0.07* vs 1.90 ± 0.02 mm), end diastolic and systolic volume. Rats treated with alamandine had reduced E/E' ratio (15.16 ± 1.04* vs 26.81 ± 3.79) and increased E'/A' ratio (1.09 ± 0.05 vs 0.57 ± 0.07 ** P<0.01), indicating the improved diastolic cardiac function. The reduced myocardial performance index (0.74 ± 0.06* vs. 1.24 ± 0.15) in alamandine treated rats demonstrated an improvement of global cardiac dysfunction. Histological analysis also revealed that alamandine attenuated ISO induced increase in cardiomyocyte size (372.46 ± 11.13** vs 551.99 ± 11.79 μm
2
) and myocardial fibrosis (1.39 ± 0.16 ** vs 4.57 ± 0.35), along with reduced mRNA expression of hypertrophy biomarkers atrial natriuretic peptide (2.45 ± 0.71** vs 8.08 ± 0.74), brain natriuretic peptide (2.86 ± 0.35 ** vs 12.53 ± 1.12), beta myosin heavy chain (1.71 ± 0.25* vs 5.38 ± 0.95) and fibrosis genes – collagen-1 (1.97 ± 0.45* vs 4.25 ± 0.6), fibronectin (2.04 ± 0.32** vs 5.05 ± 0.74), α-smooth muscle actin (1.53 ± 0.1** vs 2.71 ± 0.17). Flow cytometry analysis unveiled that alamandine reduced neutrophil, CD8 T cells and M1 monocytes, but increased M2 monocytes of left ventricle, implying the reduction of inflammation of the heart. These data suggest that alamandine plays a cardioprotective role in improving cardiac hypertrophy and fibrosis, probably via an immune mechanism to alleviate inflammatory responses during cardiac remodeling.
Abstract P126: The Single-cell And Spatial Transcriptional Landscape Of Advanced Diabetic And Hypertensive Kidney Disease In Humans
Authors: Qiu Qiongzi , Liu Dongwei , Liu Yong , Wu XiaoFeng , Liu Yong , Liu Zhangsuo , Liang Mingyu , Wang Feng
Published: October 2023

Diabetes and hypertension, the two most common causes of chronic kidney disease (CKD), can both lead to renal inflammation and fibrosis through a complex interplay among multiple cell types. However, the similarities and differences between the two pathogenic mechanisms remain understudied, including the involvement of cell organization and related biological processes. We generated an integrative cell landscape of CKD using single-nucleus gene expression and spatial transcriptome profiling in kidney samples from three patients with advanced diabetic nephropathy (ADN), three patients with advanced hypertensive nephropathy (AHN), and two normal controls. We obtained a total of 56,131 nuclei and 3,992 spatial spots to investigate the cell composition and the context of spatial niches. Significant hallmark changes were observed in both types of CKD, including the presence of an average of 60% (SD 12%) proximal tubule cells showing injured status, fibroblasts activation, mitochondria dysfunction, and a 2.9-fold increased inflammatory immune cell infiltration such as activated T cells and macrophages. Some alterations were more pronounced in AHN, such as a notable podocyte loss, which averaged 89% in AHN versus 66% in ADN, mesangial cell activation by increased collagen production, and a 34% higher proportion of natural killer T cells. Among the predominant cell communication, integrin coding gene ITGB8 was up-regulated in diseased thick ascending limbs (combined p.adj=2.3e-139) and injured proximal tubules (combined p.adj=4.4e-92), which acts as the receptor for collagen and laminin that may play a central role in extracellular matrix remodeling surrounding tubular cells. Additionally, the SPP1-CD44 axis established a broad connection between various tubular cells and pan-immune cells, potentially leading to the wide range of inflammatory responses. The co-localization pattern of this interaction was further supported by contextual evidence derived from spatial niches. Our findings provide a cell landscape of advanced diabetic and hypertensive CKD in humans, shedding light on the cellular and molecular basis of these diseases.
Abstract P128: Detection Of Congenital Intrahepatic Vascular Shunt In C57BL/6 Mice
Authors: Yeoh Beng San , Golonka Rachel , Saha Piu , Kandalgaonkar Mrunmayee , Vijay-Kumar Matam , Joe Bina
Published: October 2023

Portosystemic shunt (PSS) is an abnormal vein that leaks blood from portal vein into systemic circulation, thus bypassing the liver. We previously reported its sporadic occurrence as a congenital defect in C57BL/6 mice as well as in humans. PSS results in vascular, hepatic and metabolic anomalies. Therefore, in experimental protocols using C57BL/6 mice, ones with PSS should be identified as outliers. Accordingly, we sought methods to discern 8-weeks-old male C57BL/6 mice (n=6) as non-PSS or PSS mice. Serum total bile acids (TBA) is a
bona fide
biomarker of PSS in mice (non-PSS: 6.1±1.0
vs
PSS: 80.6±8.2 μM; p<0.001), but utility of this biomarker is limited by its cost and invasiveness, particularly if large numbers of mice are to be screened. This led us to investigate whether use of urine might serve as a simple, inexpensive, non-invasive means of PSS diagnosis. Since urinary TBA were comparable between non-PSS (4.1±1.3 μM) and PSS mice (4.8±1.7 μM; p=0.45), we asked whether there are other urinary metabolites that could be exploited as biomarkers. Nuclear magnetic resonance-based metabolomics uncovered that Krebs cycle intermediates,
i.e.
, citrate (non-PSS: 1.0±0.1
v
s PSS: 1.6±0.04; p<0.001), α-ketoglutarate (non-PSS: 1.0±0.1
v
s PSS: 3.6±0.2; p<0.001), and fumarate (non-PSS: 1.0±0.2
v
s PSS: 3.7±0.4; p<0.001) were strikingly elevated (expressed in fold change) in the urine of PSS mice. We leveraged the pH-lowering properties of such metabolites as the basis for two urine-based screening tests. Firstly, using pH test strips with a 5.5-8.0 range, we detected the differences in their urinary pH (non-PSS: 6.3±0.1
v
s PSS: 5.6±0.1; p<0.001). Secondly, the difference in urinary pH was additionally quantified using the phenol red assay (non-PSS: 0.9±0.1
v
s PSS: 0.2±0.03 at OD
560nm
; p<0.001). Using a larger cohort of non-PSS (n=44) and PSS (n=27) mice, we determined that the urinary phenol red assay had an accuracy of 95.8%, sensitivity of 96.3%, and specificity of 95.5% in identifying PSS mice. Taken together, these results demonstrate the feasibility of using urine as a liquid biopsy to screen for murine PSS. Application of our urinary PSS screening protocols importantly enables stratification of PSS mice, which confound cardiovascular and metabolic studies.
Abstract P130: Acute Angiotensin-(1-7) Infusion Does Not Improve Blood Pressure Or Leg Blood Flow In Participants With Peripheral Arterial Disease
Authors: Miller Amanda J , Luck Jonathan Carter , Blaha Cheryl , Cauffman Aimee , Aziz Faisal , Radtka Josh , Proctor David , Leuenberger Urs , Arnold Amy
Published: October 2023

Background:
Peripheral arterial disease (PAD) is an atherosclerotic disease characterized by progressive narrowing of the arteries and pain in the lower extremities. Despite high clinical impact, our understanding of the causes and optimal therapies for PAD remains incomplete. Emerging evidence suggests that angiotensin (Ang)-(1-7), a protective renin-angiotensin system hormone, improves blood vessel function and reduces inflammation to protect against atherosclerosis in animal models; however, there are no data in clinical populations. Thus, in this study, we tested the hypothesis that Ang-(1-7) can decrease blood pressure and improve leg blood flow in PAD.

Methods:
PAD participants with intermittent claudication (n= 6, 2 females, 67±7 years) received intravenous infusion of Ang-(1-7) or saline on separate days in a randomized, double-blind, placebo-controlled, crossover study. Ang-(1-7) was infused in escalating doses at 1, 2, 4, 8, and 12 ng/kg/min, with each dose held for 10 minutes. Blood pressure (finometer), heart rate (electrocardiography), femoral blood flow (duplex Doppler), and muscle oxygen saturation (near-infrared spectroscopy) were measured continuously before and during the infusion. Data are shown as change from baseline (Δ mean±SEM).

Results:
Ang-(1-7) did not significantly alter systolic blood pressure (Ang: 7 ± 3 vs saline: 2 ± 2 mmHg, p = 0.16), diastolic blood pressure (Ang: 2 ± 2 vs saline: 3 ± 1 mmHg, p = 0.75), or heart rate (Ang: 0 ± 1 vs saline: 2 ± 2 beats/minute, p = 0.13). Ang-(1-7) also did not significantly increase femoral artery blood flow (Ang: 7.28 ± 14.23 vs saline: 14.35 ± 27.48 mL/minute, p = 0.85) or calf muscle oxygenation (0 ± 1 vs saline: 1 ± 1 %SpO
2
, p = 0.88) in the participants’ symptomatic leg.

Conclusions:
Acute infusion of Ang-(1-7) at low doses is not sufficient to lower blood pressure or improve measures of leg blood flow in participants with PAD. It is possible that higher or more sustained doses of Ang-(1-7) or intervening earlier in the disease process may be more effective, however, this has not been tested.
Abstract P133: NaCl And Insulin Regulate Urate Transporter 1 Via Phosphorylation
Authors: Fujii Wataru , Yamazaki Osamu , Shibata Shigeru
Published: October 2023

Objective:
Hyperuricemia frequently associates with hypertension and diabetes. Previously, we demonstrated that insulin positively regulates urate transporter 1 (URAT1) in renal proximal tubules; yet the detailed mechanisms remain unclear. We here investigated the role of phosphorylation as a potential mechanism regulating URAT1.

Methods:
We screened potential phosphorylation sites in HEK cells expressing human URAT1 using phospho-Akt substrate motif antibody. Identified sites were confirmed by in vitro kinase assay and the creation of site-specific phosphorylation antibodies. Functional significance of identified sites was evaluated by cell surface biotinylated assay and Western blotting. As upstream signals, we tested the effects of insulin and NaCl in HEK cells expressing URAT1.

Results:
Western blot using phospho-Akt substrate motif antibody indicated that URAT1 was phosphorylated in HEK cells. Motif search identified two potential phosphorylation sites, T350 and T408 located at the intracellular regions. In ADP-glo assay, phosphorylation of URAT1 by Akt was significantly reduced when both sites were mutated to non-phosphorylatable Ala (T350A/T408A). T408A but not T350A showed decreased N-glycosylation in Western blotting. Biotinylated Western blotting confirmed that the cell-surface expression was significantly reduced in T408A-URAT1, indicating that T408 phosphorylation regulates URAT1 trafficking. Phosphorylation of T408 was confirmed by creating phospho-specific antibodies against this site. As an upstream signaling, insulin increased URAT1 at the cell surface in HEK cells, an effect that was not observed in T408A-URAT1. In kinase screen, we found that Sgk1, PKA, and PKG also phosphorylate URAT1-T408 besides Akt. NaCl increased Sgk1 and T408 phosphorylation, which resulted in increased cell surface URAT1 levels in HEK cells. In contrast, NaCl did not alter cell surface URAT1 levels in HEK cells expressing T408A-URAT1.

Conclusion:
These data indicate that insulin and NaCl promote membrane trafficking of URAT1 through T408 phosphorylation via Akt and SGK1, respectively. This mechanism could contribute to the co-occurrence of hyperuricemia in patients with hypertension and diabetes.
Abstract P139: Gender Affirming Hormone Therapy In The Hypertensive Male Rat Has Associated Effects On Cardiovascular Health
Authors: Crudup Breland , Mallette Jordan , Willis Alex , Cockrell Kathy , Yanes Cardozo Licy , Alexander Barbara T
Published: October 2023

Transgender females (
TGF
) are born biologically male, but identify as female. TGFs undergo Gender-Affirming Hormone Therapy (
GAHT
) to match their physical and sex characteristics with their perceived gender. Several studies indicate that GAHT is associated with increased cardiovascular (
CV
) risk. Previously, we reported that GAHT, 17β-Estradiol (
E2
) supplementation with androgen suppression, in the normotensive male Sprague Dawley (
SD
) rat is associated with loss of lean mass and increased markers of CV risk. Yet, the effect of GAHT in the presence of preexisting hypertension and renal injury is unknown. Thus, this study tested the hypothesis that GAHT in the male spontaneous hypertensive rat (
SHR
) is associated with increased CV and renal risk.

Methods:
Male SHRs were randomly assigned to 2 groups:
Control
(n=4) and
E2
[5 mg/day, pellet sc, replaced every 3 weeks, n=6]. E2 was initiated at 19 weeks of age at a dose to suppress endogenous testosterone coupled to elevated E2.

Results:
(
Table
) At 49 weeks of age (equivalent to a 40 year old man), body weight and total lean mass (EchoMRI) were significantly decreased in E2 SHR; as previously observed in E2 SD. Yet, total fat mass (EchoMRI) was significantly decreased in E2 SHR; moreover, 24 hour urinary proteinuria and cystatin C (ELISA) were also significantly decreased. Hypertension and renal injury are androgen-dependent in male SHR. Thus, despite the increase in E2 in the male SHR, androgen suppression induced by GAHT was renoprotective. Further studies will determine relevance of the SHR as a model of GAHT and explore long-term effects of E2.
Abstract P140: Impact Of Ovariectomy On Aldosterone And Blood Pressure In Lysine-Specific Demethylase 1 (LSD1) Deficient Mice
Authors: Stanton Ana Maria , Aljaibeji Hayat , Gholami Shadi K , Parksook Wasita , Ding Miao , Gomez Dulce H , Romero Jose R , Pojoga Luminita H , Williams Gordon H , Adler Gail K
Published: October 2023

LSD1 regulates steroid receptor function including estrogen and mineralocorticoid receptor. Women of African descent who carry the LSD1 risk allele rs587168 develop salt-sensitive hypertension and aldosterone (ALDO) dysregulation. This phenotype is observed in women above the age of 50 but not below the age of 50, which raises the question whether ovarian function affects the relationship between blood pressure (BP) and LSD1. Therefore, we hypothesized that ovariectomized (OVX) LSD1
+/–
female mice will exhibit higher systolic BP (SBP) on liberal salt (LibS) diet as compared to intact LSD1
+/–
female littermates. OVX was performed at 40 weeks of age, animals were fully acclimated to tail-cuff BP measurements, and BP was assessed on a LibS diet (1.6% NaCl Purina Chow) at 65 weeks of age, followed by euthanasia of animals and tissue collection. OVX females exhibited lower uterine weight (OVX LSD1
+/–
0.1 ± 0.03 g vs intact LSD1
+/–
0.2 ± 0.02 g,
P
=0.013) demonstrating OVX was successful. On a LibS diet, 24-h urinary Na
+
was similar between groups (OVX LSD1
+/–
0.37 ± 0.07 mEq vs intact LSD1
+/–
0.42 ± 0.09 mEq,
P
=0.678). OVX females exhibited higher SBP (OVX LSD1
+/–
121.5 ± 4.1 mmHg vs intact LSD1
+/–
107.8 ± 4.4 mmHg,
P
=0.033). 24-h urinary ALDO corrected for urinary creatinine was lower (OVX LSD1
+/–
29.2 ± 2.0 pg/mcg vs intact LSD1
+/–
59.8 ± 7.6 pg/mcg,
P
<0.001), consistent with a volume expanded state. In Conclusion, OVX increased BP in LSD1
+/-
mice, likely related to a mineralocorticoid receptor-mediated volume expansion. This raises the possibility that the reason younger women (<50 years) with LSD1 risk allele do not have salt-sensitive BP is related to ovarian hormones.
Abstract P141: Association Of Female Sex With Outcomes Of Hypertensive Emergencies
Authors: Seok Minji , Muhyieddeen Amer , Gulati Martha
Published: October 2023

Introduction:
There are well established sex differences in incidence and degrees of hypertension. We conducted an analysis aimed at uncovering sex differences in the outcomes amongst patients that were admitted due to hypertensive emergency.

Methods:
We analyzed the 2020 National Inpatient Sample to evaluate patients primarily admitted for hypertensive emergencies and then further stratified these patients by sex. To discern potential correlations, we used logistic and linear regression analyses, factoring in potential confounding variables. We considered results statistically significant when the 2-tailed p-value was <0.05.

Results:
In 2020, there were 1,221,535 hospitalizations for a principal diagnosis of hypertensive emergency, including 581,855 (47.6%) females. After accounting for various factors such as age, race, hospital bed size, location, teaching status, insurance coverage, income level, and Elixhauser comorbidities, female patients admitted for hypertensive emergency exhibited a lower rate of in-hospital mortality (aOR 0.82, 95% CI 0.77-0.87), vasopressor initiation (aOR 0.66, 95% CI 0.60-0.73), mechanical circulatory support (aOR 0.47, 95% CI 0.37-0.59), and hemodialysis initiation (aOR 0.95, 95% CI 0.92-0.98) when compared with males (Figure 1).

Conclusion:
In hospital admissions for hypertensive emergency in 2020, females had better outcomes when compared with males. Further research is required to uncover why such sex differences exist.
Abstract P145: Sodium Potassium Ratio And Blood Pressure Levels In Adults
Authors: Callo Quinte Gabriela , MILL JOSE GERALDO
Published: October 2023

Background/Objectives:
To assess the association between Sodium-potassium ratio and blood pressure levels in adults.

Subjects/Methods:
In 396 randomly distributed residences, we carried out cross-sectional measurements on participants adults from Vitória, a southeastern city in Brazil. Anthropometry, blood pressure, and fasting blood were measured on the same day by trained personnel at the University research clinic. The blood pressure mean was calculated from 2 measurements after 5 minutes of rest. The Na/K ratio was calculated from the 24-hour urine collection carried out after participants received the instructions (the first collection in a plastic cup (0.7 L), then transferring the content to the storage bottle (2 L), and keeping it in the refrigerator). We considered valid 24-hour urine collections for those with collection times between 23 and 25 hours, no report of urine loss, and volume >500 mL. A questionnaire was applied for sociodemographic variables. We performed ANOVA to compare variances across the Na/K tertile means and blood pressure and crude and adjusted linear regressions to assess the associations. Statistical significance was established in p < 0.05.

Results:
From 272 remaining participants with valid 24-hour urine, Na, K, and blood pressure data, 54% were girls, with a mean age of 44 ± 14 years old balance between age groups and no difference (p > 0.05) between genders. A significant increase in Systolic 1.53 (CI 95%: 0.26 -2.80) and Diastolic 1.27 (CI 95%: 0.54 -2.00) blood pressure was related to the Na/K ratio increase, even after adjusting for sex, BMI, and skin color.

Conclusions:
The sodium-potassium ratio is associated with blood pressure levels increment. These findings suggest the importance of dietary interventions to promote a balanced Na/K ratio, which may contribute to preventing and managing high blood pressure levels in adult populations.
Abstract P146: Environmental Exposures And The Development Of Hypertension In A Prospective US Based Cohort Of Women
Authors: Chen Jie , Hart Jaime E , Laden Francine
Published: October 2023

Environmental exposures including noise and air pollution have been linked to increased hypertension risk, whereas greenspace exposure may decrease hypertension risk. Previous studies have primarily focused on the impact of individual environmental exposures. However, people are exposed to multiple correlated environmental factors simultaneously. We aimed to assess the associations between exposure to multiple environmental exposures and hypertension development in the US-based prospective Nurses’ Health Study II (NHSII). We followed 106,409 participants in NHSII from the enrolment (1989) to the diagnosis of hypertension, death, or end of follow-up (2017), whichever came first. We appended multiple environmental factors including air pollution, noise, light at night, temperature, and greenspace at participants’ residential addresses histories (updated every two years). We calculated 24-month average exposure and cumulative average exposure for each exposure. We applied time-varying Cox proportional hazards models, adjusting for potential confounders including age, race, lifestyle factors, and individual- and area-level socioeconomic status to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident hypertension. We observed 35,155 incidents of hypertension during a follow-up period of 1,947,929 person-years. The average age of the study participants during the follow-up was 45.5 ± 9.3 years. Single exposure models demonstrated positive associations with air pollution, noise, summer maximum temperature, and a negative association with greenness (Table 1).
Abstract P155: Low Vegetable Consumption Doubles The Risk Of Stroke Among Hypertensives In West Africa
Authors: Asowata Osahon J , Bodunde Ifeoluwa , Danladi David K , Akpa Onoja M , Fakunle Adekunle , SARFO FRED S , Akpalu Albert , Obiako Reginald , Wahab Kolawole W , Osaigbovo Godwin , Ogbole Godwin , Akinyemi Joshua , Owolabi Lukman , Komolafe Morenikeji , Akinyemi Rufus O , Ovbiagele Bruce , Okekunle Akinkunmi P , Owolabi Mayowa
Published: October 2023

Background:
Low vegetable consumption and hypertension are independently associated with stroke, but little is known about the interaction of these two factors. This study evaluated the interaction of low vegetable consumption with hypertension in stroke occurrence among West Africans.

Methods:
The dataset for this study was from the 3684 stroke case-control pairs matched for age, sex, and ethnicity in the SIREN Study. Based on clinical examination, stroke assessment was confirmed with cranial computed tomography or magnetic resonance imaging. Controls were recruited from communities around hospitals where stroke cases were recruited. A conditional logistic interaction model was fitted to assess the relative excess risk due to interaction (RERI), interaction attributable proportion (AP), and synergy index of hypertension and low vegetable consumption in stroke manifestation, adjusting for relevant covariates at a two-sided
P
<0.05.

Results:
Participants' mean age was 59.0±14.0 years, 54.2% (4984 of 7368) were males, 62.8% (4627 of 7368) had vegetable consumption of ≤5 servings/week and 76.6% (5643 of 7368) were hypertensives. The odds ratio and 95%CI for stroke among hypertensives with low vegetable consumption was 31.7 (21.3, 42.3) {with RERI of 15.5 (8.7, 22.2);
P
<0.0001, AP of 49.0%, and the synergistic interaction of 2.0 (1.7, 2.4);
P
<0.0001}, but 15.7 (10.6, 23.4) among hypertensives without low vegetable consumption.

Conclusion:
Low frequency of vegetable consumption potentially aggravates the stroke odds, even with hypertension. Interventions promoting vegetable consumption might be promising in alleviating stroke burden and associated complications.
Abstract P158: Associations Of Orthostatic Hypotension And Resting Hypertension With Biomarkers Of Subclinical Cardiovascular Disease
Authors: Petriceks Aldis H , Appel Lawrence J , Miller Edgar R , Mitchell Christine , Schrack Jennifer , Wanigatunga Amal , Michos Erin D , Juraschek Stephen P
Published: October 2023

Background:
Orthostatic hypotension (OH) is associated with cardiovascular disease (CVD), but mechanisms for this relationship are unclear.

Objective:
To determine associations between orthostatic, seated, or standing hypotension with two biomarkers of subclinical injury—high sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)—relative to orthostatic, seated, or standing hypertension (HTN).

Methods:
We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You (STURDY) using standardized seated and standing blood pressure (BP) assessments. We defined OH as a drop in systolic BP (SBP) ≥20 or diastolic BP (DBP) ≥10 mm Hg upon standing; seated or standing hypotension as BP ≤105/≤65 mm Hg; orthostatic HTN as an increase in BP ≥20/≥10 mm Hg upon standing; and seated or standing HTN as BP ≥140/≥90 mm Hg. Associations between BP phenotypes and serum Hs-cTnI and NT-proBNP were determined using mixed-effects Tobit models.

Results:
Of 673 participants (mean age 76.5 ± 5.4 years; 43% female; 17% Black), 63% had prior CVD. Those with seated HTN had a 10.2% greater hs-cTnI (
P
= 0.001) and 11.0% greater NT-proBNP (
P
= 0.002) than those without seated HTN (
Table)
. Participants with standing HTN had an 8.6% (
P
= 0.004) greater hs-cTnI and 11.8% greater NT-proBNP (
P
= 0.0005) than those without standing HTN. No hypotensive phenotypes were associated with biomarkers.

Conclusions:
Both seated and standing HTN are associated with greater hs-cTnI and NT-proBNP, but hypotensive phenotypes were not. Hypoperfusion may not be a major contributor to subclinical cardiac injury among older adults with OH.
Abstract P162: Gender Differences In Hypertension Risk Factors In Non-hispanic Asian Adults In The United States
Authors: Tanglai Wirampa , Cajita Mia
Published: October 2023

Introduction:
Hypertension (HTN) is a leading cause of comorbidity and mortality worldwide. Limited studies discussed the risk prediction for HTN prevalence among non-Hispanic Asian adults. We aim to examine gender differences in HTN prevalence and associations between risk factors and hypertension in non-Hispanic Asian adults in the US.

Methods:
We included non-Hispanic Asian adults (≥20 years) from the 2017-2018 National Health and Nutrition Examination Surveys. HTN was defined as blood pressure ≥140/90 mmHg or self-reported use of antihypertensive medication. We used hierarchical logistic regression to determine the odds of HTN diagnosis for different gender groups.

Results:
Among the 811 participants, 29.60% of men (111 of 375) and 28.90% of women (126 of 436) had HTN. The study found that the odds of HTN diagnosis increased with age for both men and women. Men aged 30-80 years had greater odds of HTN diagnosis compared to those aged 20-29 years, with odds ranging from 14.85 to 124.85. Women aged 50-80 years had greater odds of HTN diagnosis compared to those aged 20-29 years, with odds ranging from 22.74 to 67.33 (Table). Body mass index was a stronger predictor of HTN among women than men. In men, a higher waist-to-height ratio was associated with increased odds of HTN diagnosis. In women, higher fasting blood glucose and serum uric acid levels were stronger predictors of HTN.

Conclusion:
This study discovered substantial gender differences in the risk factors for HTN among non-Hispanic Asian adults living in the United States, with age shown to be a major risk factor.