bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 115: Soluble (pro)renin Receptor Contributes To Endotoxin-induced Septic Shock And Aki In Mice
Authors: Zheng Huaqing , Fu Ziwei , Wang Fei , kaewsaro kannaree , Yang Tianxin
Published: September 2022

Sepsis associated acute kidney injury (S-AKI) is a life-threating disease with poorly defined mechanisms and limited therapeutic options. Here we examined the role of site-1 protease (S1P)-derived soluble PRR (sPRR) in the S-AKI model induced by lipopolysaccharide (LPS). Male 10-week-old B6129SF1/J mice were pretreated with a S1P inhibitor PF-429242 (PF) at 20 mg/kg/day via minipump and treated with a single s.c. injection of LPS at 10 mg/kg and monitored for 24 hours. By radiotelemetry, LPS induced fall in mean arterial pressure (MAP) (Δ mmHg: -14.98 ± 4.13 in LPS+PF group
vs
. -23.15 ± 1.82 in LPS+ Vehicle group; n = 6, p < 0.05) and heart rate (HR) (Beats/min: -78.60 ± 20.73 in LPS+PF group
vs
. -133.35 ± 30.92 in LPS group, n = 6, p < 0.05), which was significantly attenuated by PF treatment. In parallel, renal dysfunction as reflected by the rises in plasma creatinine and BUN along with albuminuria, urinary excretion of NGAL and Kim-1 were all improved. Similar improvement was observed for infiltration of macrophage as assessed by immunofluorescence detection of F4/80 as well as renal mRNA expression of M1 markers such as iNOS, IL-1β, IL-6, and TNFα. The results from the pharmacological study were validated using a recently generated mouse model of mutagenesis of the cleavage site of PRR (termed Mutant mice). LPS-induced hypotensive response, renal dysfunction, the markers of renal injury and inflammation and M1 activation were all improved in Mutant mice as seen with PF treatment. LPS induced a 3.35-fold increase in plasma sPRR which was attenuated by PF or in Mutant mice. By immunofluorescence, LPS-induced PRR expression was largely restricted to renal medullary intercalated dells. In cultured RAW264.7 macrophage cells, recombinant sPRR treatment at 30 nM directly promoted macrophage migration and stimulated mRNA levels of M1 markers, all of which were attenuated by losartan. Taken together, the present study suggests that (1) S1P-derived sPRR contributes to LPS-induced septic shock and AKI, and (2) within the kidney, LPS-induced sPRR originates from intercalated cells and may act in a paracrine manner to activate AT1R on macrophages to induce pro-inflammatory response.
Abstract 118: P2X7 Receptor Contributes To Angiotensin II-induced Hypertension, Vascular Injury And Cd8
+
T Cell Activation
Authors: Paradis Pierre , Shokoples Brandon , Berillo Olga , Comeau Kevin , Higaki Akinori , Caillon Antoine , Ferreira Nathanne d , Schiffrin Ernesto L
Published: September 2022

Introduction:
Innate and adaptive immune cells contribute to hypertension and end-organ damage. High blood pressure (BP) causes cardiovascular injury and the release of damage-associated molecule patterns such as adenosine triphosphate (ATP). ATP can bind to the purinergic receptor P2X7 (P2RX7) on innate immune cells triggering interleukin-1β release, which drives further immune activation.

Hypothesis:
We hypothesized that
P2rx7
knockout or P2RX7 antagonism would blunt angiotensin II (AngII)-induced BP elevation and cardiovascular injury through decreased immune activation.

Methods:
Ten-to-12-week-old male C57BL/6J wild-type (WT) and

P2rx7
-/-

mice were infused or not with AngII (1000 ng/kg/min) for 14 days. A second group of AngII-infused WT mice was also infused with the P2RX7 antagonist AZ10606120 (694 ng/kg/min) or vehicle. BP was determined by telemetry, plasma ATP using a bioluminescence assay, mesenteric artery function using pressurized myography, cardiac left ventricle (LV) function and mass by ultrasound and activated immune T cell infiltration in aortic perivascular adipose tissue (PVAT) by flow cytometry.

Results:
AngII increased plasma ATP in WT mice (4.4±1.2 vs 2.0±0.9 μM,
P
<0.05). AngII-induced systolic BP elevation was reduced by
P2rx7
deficiency (164±3 vs 176±2 mm Hg,
P
<0.05) or P2RX7 antagonism (143±5 vs 170±5 mm Hg,
P
<0.01). AngII decreased LV fractional shortening (FS, 32.5±3.1% vs 43.8±2.4%,
P
<0.05) and increased LV mass/body weight (BW) in WT mice (LVmass/BW, 6.3±0.2 vs 4.2±0.2 mg/g,
P
<0.001), which were exaggerated in

P2rx7
-/-

(FS: 20.2±3.1% and LVmass/BW: 7.2±0.5 mg/g,
P
<0.05), but not in mice receiving AZ10606120. AngII reduced the dilatation response of mesenteric arteries to acetylcholine in WT (61±7 vs 83±4%,
P
<0.05), but not in

P2rx7
-/-

or AZ10606120-treated mice. AngII increased CD69
+
CD8
+
T cell infiltration in aortic PVAT of WT (60±16 vs 16±3 cells/aortic PVAT,
P
<0.001), but not in

P2rx7
-/-

or AZ10606120-treated mice.

Conclusion:
P2rx7
knockout or antagonism attenuates AngII-induced BP elevation, vascular injury, and infiltration of activated CD8
+
T cells into aortic PVAT.
P2rx7
knockout exacerbated AngII-induced cardiac dysfunction and hypertrophy, whereas P2RX7 antagonism did not.
Abstract 129: Role Of Human T Cells In Experimental Hypertension And Hypertensive Kidney Damage
Authors: Rahman Masudur , Arifaj Denada , Hering Lydia , Yakoub Mina , Rump Lars Christian , Stegbauer Johannes
Published: September 2022

Animal studies suggest that adaptive immunity, in particular T cells contribute to the development hypertension. Due to the complex pathophysiological interactions in vivo, the impact of human T cells in the development of hypertension and hypertensive kidney damage is still unknown. To investigate the impact of human T cells, we transferred T cells from treatment resistant hypertensive patients (TRH) and healthy controls (controls) into immunodeficient NOD.Cg-Prkdcscid H2-K1tm1Bpe H2-D1tm1Bpe Il2rgtm1Wjl/SzJ (NSG-(KbDb)null) mice to establish a humanized mouse model. Hypertension was induced by angiotensin (Ang)II (500ng/kg/min) infusion for 14 days. PBMCs from RHT or controls were transferred to NSG-(KbDb) null mice. After ensuring T cell engraftment, blood pressure (BP) was measured by radiotelemetry. At baseline, systolic BP did not differ, however, systolic BP in response to AngII was increased in NSG-(KbDb) null mice receiving PBMCs from TRH compared to controls (week 1: 133±6 vs. 162±3mmHg, p<0.01; week 2: 141±6 vs. 158±7mmHg, n=5-6, p<0.05). Moreover, endothelial-dependant vasorelaxation was significantly impaired in isolated perfused kidneys of NSG-(KbDb) null mice receiving PBMCs from TRH compared to controls. Proportions of effector memory CD4 and Th17 CD4 cells in the spleens and kidneys of NSG-(KbDb) null mice engrafted with PBMCs from TRH were significantly higher compare to controls. Furthermore, renal mRNA expression of TNFα derived from human T cells (p<0.05) and renal perivascular T cell infiltration were significantly higher in NSG-(KbDb) null mice engrafted with PBMCs from TRH compared to controls. Overnight incubation of aortic rings with human TNFα impaired endothelial-dependen vasorelaxation compared to untreated aortic rings (p<0.01). Finally, NSG-(KbDb) null mice engrafted with PBMC from TRH were treated with the TNFα inhibitor etanercept. TNFα inhibition attenuated the systolic BP response to AngII compared to untreated mice (132±1 vs. 160±2mmHg, n=6, p<0.01).The present results suggest that pro-inflammatory cytokines released by T cells from patients with TRH directly influence the development of hypertension and therefore may have a pathophysiological relevance in the genesis of human hypertension.
Abstract P012: Agreement In Same Day Research-Quality And Casual Systolic Blood Pressure Measurements: Insights From BETTER-BP
Authors: Maidman Samuel D , Adhikari Samrachana , Levy Natalie , Lee Carson , Hanley Kathleen , Shimbo Daichi , Gutierrez Yasmin , de Brito Stefany , Qian Kun , Fonceva Anamarija , Dodson John A
Published: September 2022

Introduction:
Prior studies suggest that BPs measured casually during routine clinic workflow are higher than research-grade measurements. However, BPs in these studies were typically collected on different days. We sought to compare the influence of day of assessment on this difference, within the context of an ongoing randomized trial.

Methods:
This is a cross-sectional interim analysis of the BETTER-BP trial, which examines the effect of behavioral economic incentives for medication adherence on BP. Our study focused on concordance between baseline BP measurements and did not analyze trial outcome data. We included the first 171 participants (1/1/20-3/31/22). Research BP was measured in a seated position after a 5 minute rest period using a standard cuff (Omron HEM 907-XL). Casual BP measurements (most recent recording prior to the research measurement) as well as baseline characteristics were abstracted from the EHR. Participants were divided into two groups based on whether their casual BP was measured on the same day (vs different day) as their research BP. The mean systolic BP (SBP) obtained for research versus casual measurements were compared, for the two separate groups, using paired T-tests.

Results:
Mean age was 55 years, 49.1% were female, 93.2% were nonwhite, and 48.5% were Spanish-speaking. Common comorbidities were diabetes (48.5%) and obesity (49.1%). Among the 132 patients with same day measurements, mean research SBP was 139.2 ± 20.4 mmHg and casual SBP was 137.9 ± 16.4 mmHg (mean within person difference=1.3 mmHg; P=0.259). Among the 39 patients with different days of measurement (median 14 [IQR 6-47] days), mean research SBP was 136.5 ± 23.3 mmHg and casual SBP was 144.2 ± 18.9 mmHg (mean within person difference= -7.7 mmHg; P=0.007). Casual SBP was higher among patients with measurements on different days compared to patients with same day measurements (P=0.043).

Conclusion:
SBP measured casually during clinical practice were concordant with research-quality measurements when obtained on the same day. SBP measurements differed significantly when obtained on different days. These findings suggest that prior reports showing casual BPs to be consistently higher than research BPs may have been influenced by temporal variability.
Abstract P063: Long-term Efficacy Of Atomoxetine For The Treatment Of Symptomatic Neurogenic Orthostatic Hypotension
Authors: Urechie Vasile , Rigo Stefano , Palma Jose-Alberto , Diedrich Andre , Biaggioni Italo , Kaufmann Horacio , Shibao Cyndya A
Published: September 2022

Patients with neurogenic orthostatic hypotension (NOH) are at risk for syncope, falls and have poor quality of life. Only two drugs (midodrine, droxidopa) are FDA-approved for the treatment of NOH. We previously reported that atomoxetine, a norepinephrine transporter inhibitor, acutely improved upright blood pressure and symptoms in NOH, mostly in multiple system atrophy (MSA) patients. However, the long-term efficacy of atomoxetine for the treatment of NOH is unknown. We hypothesize chronic treatment with atomoxetine improves pre-syncopal symptoms in NOH We conducted multicenter, randomized, double-blind, placebo-controlled, 2X2 crossover design with initial atomoxetine dose-titration phase. NOH patients were randomized to two, 4-week treatment sequence (period 1: atomoxetine (10 or 18 mg TID) followed by placebo) or vice versa (period 2). The primary outcome was a reduction in pre-syncopal symptoms using the orthostatic hypotension questionnaire (OHQ) composite score, calculated from the OH symptoms Assessment (OHSA) and the OH Daily Activity Scale (OHDAS). Secondary endpoints were orthostatic vital signs. We screened 68 patients, 48 were enrolled in the dose-titration and 40 were randomized (68 ± 8 yo, %60 males, BMI 26.2 ± 4.8 kg/m
2
). We found no difference in the OHQ score between atomoxetine and placebo at 2-week (4.8±2.4 vs 4.5±2.1, P=0.73). Sub-analyses between MSA and non-MSA patients showed significant decline in OHSA with atomoxetine (2.6±1.8 vs 3.6±1.8, p=0.03) in non-MSA patients, specifically in vision disturbance (p=0.04) and in weakness (p=0.03). At 4-week, atomoxetine effect on upright SBP persisted (3.4±20.61 vs. -5.5±14.82 mm Hg, p=0.037). Atomoxetine was well-tolerated. Even though we found no significant reduction in OHQ with atomoxetine. Sub-analyses based on diagnosis, found that non-MSA patients had a significant improvement in OHSA. Atomoxetine effect on upright SBP persisted after 4-week treatment suggesting no tachyphylaxis.
Abstract P067: Sex-Specific Protection Of Fermentable Dietary Fiber On Salt-Sensitive Hypertension And Renal Function
Authors: Abais-Battad Justine M
Published: September 2022

Our recent data show that female Dahl Salt-Sensitive (SS) rats are significantly protected from salt-induced hypertension and renal injury and have stark differences in gut microbiota composition compared to males. Gut-derived metabolites are gaining recognition as mechanistic links between the microbiota and disease. One such metabolite is propionate, a protective short-chain fatty acid byproduct of bacterial fiber fermentation. Metabolomics revealed a specific elevation in serum propionate in female versus male SS rats after high salt (HS) (40.3±3.8 vs 24.4±4.2 μM, female vs male, p<0.02, n=6), and propionate administration to male SS rats blunts salt-induced elevations in mean arterial pressure and albuminuria (MAP, HS21: 160.5±6.6 vs 141.8±3.5 mmHg, p<0.05; albuminuria: 437.8±108.6 vs 263.6±50.33 mg/day, p<0.19, control vs propionate, 200mM p.o.; n=3-4). Therefore, the current study hypothesized that substitution of non-fermentable fiber cellulose with the fermentable fiber inulin (AIN-76A, Dyets Inc), a known precursor of short-chain fatty acids, would attenuate salt-sensitivity in males. Males and females were placed on the 0.4% NaCl (LS) inulin diet for one week prior to the switch to a 4.0% NaCl (HS) inulin diet for 4 weeks (inulin-M: n=7, inulin-F: n=6). Controls were maintained on either LS or HS diets containing cellulose (control-M: n=9, control-F: n=11). While there were no significant MAP differences observed in males, the inulin diet significantly reduced albuminuria (370.8±32.4 vs 174.4±30.0 mg/day on HS28, control-M vs inulin-M, p<0.001), reduced CD45+ renal leukocytes (35% reduction, p<0.03), reduced BUN (21.6±2.0 vs 15.4±0.5 mg/dL, p<0.05), and increased creatinine clearance (0.44±0.02 vs 0.55±0.02 ml/min/g KW, p<0.001). In females, inulin significantly lowered MAP (170.2±6.2 vs 154.6±4.5 mmHg on HS28, control-F vs inulin-F, p<0.01), albuminuria (180.3±27.4 vs 68.0±8.3, p<0.001), BUN (21.7±1.2 vs 17.9±0.6 mg/dL, p<0.05), and improved creatinine clearance (0.53±0.04 vs 0.71±0.05 ml/min/g KW, p<0.05). In summary, substitution of the fermentable fiber inulin reduced blood pressure only in females, but all other measures indicate improved renal injury, function, and inflammation in both sexes.
Abstract P070: Vascular Conditioning Exercise Acutely Enhances Endothelial Function In Young Adults
Authors: Tavoian Dallin , Mazzone Josie L , Craighead Daniel H , Bailey E. Fiona
Published: September 2022

Introduction:
Vascular conditioning exercise (VCE), otherwise known as high-resistance inspiratory muscle strength training, is a potent non-pharmacological therapy to reduce blood pressure. When performed daily for 6 weeks, systolic blood pressure is reduced by ~6-10 mmHg on average, in part, by increasing nitric oxide-mediated endothelial dependent dilation (EDD). While the adaptations to long-term VCE have been described, the acute effects of VCE that may mediate the long-term vascular adaptations have not been thoroughly investigated.

Hypothesis:
We assessed the hypothesis that a single bout of VCE would increase EDD for at least 40 minutes after exercise completion, while arterial stiffness would not be affected.

Methods:
Nitric oxide-mediated EDD and ischemia-induced maximal shear rate were assessed with brachial artery flow-mediated dilation, and arterial stiffness was assessed via carotid-femoral pulse wave velocity. Assessments were performed before, 10 minutes after, and 40 minutes after a single bout of VCE (5 sets of 6 breaths at 50% of maximal inspiratory pressure with 1-minute rest intervals) or a time-matched rest interval in nine young adults (22.3 ± 2.6 years; 3 male, 6 female) using a randomized crossover design, with at least 48 hours between visits.

Results:
All values are mean difference ± SD. There were no differences between interventions in EDD at baseline (0.73 ± 3.7%;
p
=0.569). EDD was significantly higher 10 minutes post-VCE, relative to the rest intervention (3.28 ± 3.37%;
p
= 0.019), but there were no differences at 40 minutes post-intervention (0.01 ± 4.46%;
p
=0.992). Further, there were no differences in maximal shear rate between measurements (all
p
-values >0.05), indicating the changes in EDD were not due to a modified hyperaemic response. Lastly, there were no differences in arterial stiffness (Baseline: 0.22 ± 0.75 m/s; Post-10: 0.26 ± 0.51 m/s; Post-40: 0.27 ± 0.33 m/s; all
p
-values >0.05).

Conclusions:
A single bout of VCE transiently enhances EDD in healthy young adults, although this effect disappears within 40 minutes of exercise completion. This acute functional response to VCE can partially explain the large improvements in EDD that are seen in response to daily VCE performance over longer periods.
Abstract P083: Progression Of Vascular Dysfunction In A Mouse Model Of Kawasaki Disease
Authors: Saiyid Alina D , Singh Shubhnita , Bruder-Nascimento Ariane , Bruder-Nascimento Thiago
Published: September 2022

Progression of vascular dysfunction in a mouse model of Kawasaki disease Alina Saiyid, Shubhnita Singh, Ariane Bruder-Nascimento, Thiago Bruder-Nascimento Kawasaki disease (KD) is an acute, self-limited vasculitis and the most common cause of acquired cardiovascular disease in young children. Although severe vascular inflammation is already well-established in KD, how the arteries functionally behave in acute and convalescent phases is poorly understood. Herein, we sought to investigate the vascular function using a mouse model of KD.KD was induced by the
Candida albicans
water-soluble fraction model (CAWS, 4mg/day for 5 days) in C57BL6/J male mice (5-6-week-old). Mice were divided into 3 groups: control (G0, PBS injections), 7-days post 1 CAWS injection (G7), and 28-days post 1 CAWS injection (G28). Heart and abdominal aorta (AA) were harvested for vasculitis characterization. Vascular function was studied in AA via wire myograph.G7 presented an increase in TNFα and IL1β gene expression in the heart and AA, but without clear vasculitis (analyzed by histology). However, G28 exhibited a severe immune cell infiltration in the aortic root, coronary arteries, and AA. In G7, AA displayed a drastic reduction in vascular response to norepinephrine [maximal response (Emax in mN): C: 5.4 ± 0.6 vs. G7: 2.0 ± 0.5*, *p<0.05], such attenuation was abolished by pre-treating the AA with L-NAME (nitric oxide synthase inhibitor). In G28, a mild change was observed in maximal response; however, increased sensitivity was found (pD2: C: 6.0 ± 0.4 vs. G28: 6.8 ± 0.3*, *p<0.05). After L-NAME pre-treatment, the difference persisted indicating a NO-dependent response. Furthermore, a severe endothelial dysfunction, characterized by impaired relaxation of acetylcholine, was observed in G28 [Emax (%): C: 85.7 ± 8.4 vs. G28: 54.8 ± 6.4*, *p<0.05].In conclusion, the acute phase of KD is associated with impaired vascular contractility via an excess of NO, which could justify some children presenting shock in clinic. In the convalescent phase (G28), the arteries are injured and likely with an irreversible phenotype. Thus, an adequate and punctual treatment for KD is highly requested.
Abstract P088: Comparison Of Lay Advisor Interventions For Hypertension Across Racial Groups In The United States
Authors: Bushweller Leila , Bhayani Vishwa , Yoshida Yilin , Wilson Gwendolyn , Stange Kurt , Saper Robert , Patil Sonal
Published: September 2022

Background:
Lay advisor interventions for hypertension are frequently tailored to a single racial group. We conducted a systematic review comparing components of lay advisor interventions for hypertension across racial groups in the US.

Methods:
Multiple databases were searched from 1980 to 2020 using relevant search terms.

Results:
Of 5986 articles, 14 studies were eligible for inclusion: 5 with predominantly white participants, 4 with Black participants, 3 with Hispanic participants and 2 with Asian participants. All studies but two were RCTs.

One study with white participants and one with Hispanic participants were clinic-based; all other studies were community-based. Lay advisors were matched to participants’ social groups in 13 studies and 1 study used health coaches with a bachelor's degree. Home visits were included in 44% (4/9) of studies with minority participants and in no studies with predominantly white participants. Most (4/5) studies with white participants included group education and one study had individual education. All studies with Black participants included only individual education. Two studies with Hispanic participants included group education while one study used health coach phone calls and home BP monitoring. Both studies with Asian participants included group education with follow-up individual education.

For BP outcomes: 3 studies with predominantly white participants, 3 with Black participants, 1 with Hispanic participants, and 2 with Asian participants showed statistically significant improvement. One health coach study with Hispanic participants showed a systolic BP reduction of 19.3 mm Hg; all other studies showed mean systolic BP improvements between 6 to 8.3 mm Hg across races. Three studies examined hypertension control outcomes, of which 2 studies with Asian participants showed improved hypertension control. Individualized low-intensity interventions were as effective as high-intensity interventions.

Conclusion:
Lay advisor interventions were effective and mainly community-based across racial groups. Individualized education by lay advisors belonging to patients’ social groups may be a feasible and effective approach for health systems that care for diverse populations.
Abstract P092: Sex Differences In Cardiometabolic Risk Factors Of Obese Adolescents
Authors: Valdez Lucrecia , AlSiraj Yasir , Huang Hong , Bauer John A , Radulescu Aurelia , Davis Dolph , Shoemaker Robin C
Published: September 2022

Background:
The prevalence of hypertension in children and adolescents is rising, with 13% having elevated blood pressure and 5% having hypertension. Sex differences play a role in cardiovascular diseases in adults but are not well defined in youth. The objective of this study is to identify sex differences in obesity-mediated cardiometabolic risk factors in adolescents.

Methods:
This is a pilot study of n=82 obese children and adolescents recruited from a High BMI Clinic. Boys (n=42) and girls (n=40) were grouped by age (greater or less than age 12). Clinical data and blood samples were collected at a single time point (initial clinic visit). Serum sterols (glucocorticoids, mineralocorticoids, and sex hormones) were quantified via LC-MS/MS. Data are mean +/- standard deviation with analysis via 2-way ANOVA.

Results:
Mean BMI was 32.9 and 37.6 kg/m2 in children under/over age 12, respectively, with no difference in boys versus girls. Systolic blood pressure (SBP) was higher in boys and girls over compared to under age 12. Girls over age 12 had higher diastolic blood pressure (DBP) compared to boys (69.4 + 8.6 versus 66.4 + 5.1 mmHG; P<0.05) which was associated with elevated aldosterone (272.5 + 369.9 versus 148.3 + 107.9 pg/mL; P<0.05) and cortisol (100.3 + 69.8 versus 63.0 + 28.9 ng/mL; P<0.05) concentrations. In contrast, there was no difference in the homeostatic model assessment for insulin resistance (HOMA-IR) between boys and girls.

Conclusions:
Despite having similar BMI and HOMA-IR, girls and boys had differences in DBP and serum sterols. Further analysis will refine associations of sex hormones with anthropometric, blood pressure, and glucose homeostasis measurements in obese girls and boys.
Abstract P093: Preterm Birth And Hypertension Severity In Youth Referred For Hypertension Disorders: A Superhero Interim Analysis
Authors: Carrasquillo Rachel A , Giammattei Victoria , Lucas Caroline B , Sethna Christine , Vincent Carol , Viviano Irina , Weaver Donald , South Andrew M
Published: September 2022

Introduction:
Pediatric hypertension (HTN) is a growing concern with short and long-term adverse health effects. While children who were born preterm (<37 weeks’ gestation) likely have an increased HTN risk, it is unknown whether preterm birth is associated with more severe HTN once diagnosed.

Objective:
Determine whether youth referred for HTN disorders who were born preterm are more likely to have worse blood pressure (BP).

Methods:
This is a cross-sectional analysis of preliminary baseline data from The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) Registry, an ongoing multicenter retrospective cohort of youth referred to subspecialty clinics for HTN disorders. Inclusion criteria were <19 years of age, initial visit 1/01/2016-12/31/2021 (index date), and ICD-10 diagnostic codes for HTN disorders. Exclusion criteria were pregnancy, kidney failure on dialysis, or kidney transplantation by ICD-10 codes. We classified BP based on age, sex, and height per pediatric guidelines. We further defined high BP as elevated BP or any stage of HTN. Preterm birth was based on ICD-10 codes at the index date. We used unadjusted generalized linear models to estimate RR with 95% CL.

Results:
In the cohort, 939/3295 (29%) identified as Black/African American, 576/3295 (17%) Hispanic/Latino, 1216/3295 (37%) were female, and the median age was 14.2 years (IQR 10.5, 16.4);1703/3295 (52%) had obesity. Only 24/3295 (1%) had an ICD-10 code for preterm birth, and 1951/3228 (60%) had stage 1 or stage 2 HTN. Preterm birth ICD-10 codes were not associated with a higher risk of high BP (RR 0.78, 95% CL 0.57 to 1.06) or a higher risk of HTN (RR 0.84, 95% CL 0.56 to 1.27).

Conclusion:
Youth referred for HTN disorders who had ICD-10 codes for preterm birth did not have worse BP compared to those without these codes. It is possible that preterm birth is not accurately documented. Ongoing analyses include obtaining actual gestational age at birth and investigating the association with target organ damage.
Abstract P103: Apelin And Elabela Attenuate The Pro-inflammatory Response In Hypoxic HTR-8/SVneo Trophoblastic Cells
Authors: Soloshenko Anna , Sun Xuming , Chappell Mark C , Yamaleyeva Liliya M
Published: September 2022

Preeclampsia is a significant pregnancy complication characterized by de novo hypertension, proteinuria, and further organ dysfunction. We previously demonstrated both cardio- and renoprotective effects by systemic activation of apelin receptor system (APJ) in preeclampsia. Although the APJ ligands apelin and elabela stimulate trophoblast cell proliferation and migration, the cellular mechanisms underlying these actions are not well understood, particularly in response to hypoxia. To examine the response of the APJ system to cellular hypoxia in human trophoblasts, HTR-8/SVneo trophoblastic cells were treated with cobalt chloride (CoCl
2:
200 μM, 24 hours) to induce hypoxic conditions. The cellular mRNA responses for sFlt-1 variants, VEGF, PLGF, IL-6, and IL-1β were determined by RT-qPCR for control and apelin- or elabela-treated cells with or without CoCl
2
. The presence of APJ mRNA was confirmed in HTR-8/SVneo cells. Hypoxia increased apelin content approximately 2-fold in both the cell lysate (723 ± 52 vs. 1216 ± 20 ng/mg protein, n=6, p<0.01) and the conditioned media (49 ± 5 vs. 102 ± 9 ng/ml, n=6, p<0.01). Elabela content also increased in the media of hypoxic cells (0.11 ± 0.01 vs. 0.14 ± 0.01 ng/ml, n=6, p<0.05), although elabela levels were 100-fold lower than apelin. Hypoxia upregulated hsFlt-1-i13 (2.6 fold), hsFlt-1-e15a (2.9 fold), VEGF (3.7 fold), PLGF (1.3 fold), and IL-6 (3.5 fold) mRNA levels. Treatment with (Pyr-1)-apelin-13, a stable APJ ligand (0.1 μM), decreased VEGF (1.2 fold; n=3, p<0.05) and IL-6 (1.4 fold, n=3, p<0.05) mRNA levels in cells exposed to COCl
2
, but had no effect in normoxic cells. Similarly, elabela (0.1 μM) downregulated VEGF (1.1 fold; n=3, p<0.05) and IL-6 (1.2 fold; n=3, p<0.05). We found no difference in sFlt-1 variants, PLGF, or IL-1β mRNAs following treatment of hypoxic cells with either peptide. We conclude that cobalt-induced hypoxia markedly increases various indices of inflammation, as well as stimulates the endogenous apelin and elabela systems in the HTR-8/SVneo cells. Furthermore, local activation of these peptidergic systems may be a compensatory response of the trophoblast cells to hypoxia as exogenous apelin and elabela treatment effectively ameliorate the hypoxia-induced pro-inflammatory milieu.
Abstract P120: Left Ventricular Hypertrophy Is Associated With Higher Cardiac Biomarkers In Patients With Covid-19
Authors: Rivera Rodriguez Beatriz , Yan Crystal , Aponte Becerra Laura X , Olarte Neal , Andrade-Bucknor Sharon
Published: September 2022

Introduction:
Left ventricular hypertrophy (LVH) is a risk factor for adverse cardiovascular outcomes such as heart failure and arrhythmia. LVH is characterized by increased left ventricular mass with myocardial fibrosis and may contribute to COVID-19-induced cardiac injury.

Hypothesis:
LVH is a predictor of poor outcomes in patients with COVID-19.

Methods:
We conducted a two-center retrospective study of 415 adult patients hospitalized with COVID-19 from March 2020 to September 2021 who had an echocardiogram performed while inpatient. Baseline characteristics, biomarkers, and hospitalization outcomes were described. LVH was diagnosed by linear measurements with echocardiography. Statistical analyses were performed using SAS 9.4 and SPSS 28. Differences between groups were determined by one-way ANOVA, Wilcoxon rank-sum, or Fisher exact test.

Results:
LVH was present in 34.2% (142/415) of patients. Compared to those without LVH, those with LVH were older (64 vs 68 years, p=0.02), heavier (84.4 vs 89.6 kg, p=0.03), and more likely to be diabetic (39.6% vs 50.0%, p=0.04), hypertensive (61.5% vs 71.8%, p=0.04), and smokers (5.1% vs 12.0%, p=0.02). NT-proBNP (1342 vs 721, p=0.02) and peak troponin I (0.03 vs 0.01, p=0.002) levels were higher in the LVH group. The LVH group had increased rates of myocardial infarction (7% vs 4%), new-onset heart failure (8.5% vs 7.3%), and mortality (35.9% vs 30%), although these findings were not statistically significant. Similarly, logistic regression models showed a sustained effect of age (OR 1.17 [CI 1.02-1.34], for every 10 years), diabetes (OR 1.53 [CI 1.02-2.29]), hypertension (OR 1.59 [CI 1.03-2.4]), and smoking (OR 2.52 [CI 1.2-5.3]) in patients with LVH; however, there was no difference between groups for all outcomes measured.

Conclusion:
LVH was significantly associated with other cardiovascular risk factors and increased cardiac biomarkers, suggesting a higher degree of cardiac injury in LVH patients with COVID-19. Although there was a higher rate of cardiovascular events and mortality in patients with LVH, these findings were not statistically significant. Studies with a larger sample size are needed to determine whether LVH is an independent predictor of COVID-19-induced cardiac injury.
Abstract P138: Novel Smooth Muscle Ca
2+
-signaling Nanodomains In Blood Pressure Regulation
Authors: Chen Yen-Lin , Daneva Zdravka , Kuppusamy Maniselvan , ottolini matteo , Baker Thomas , Klimentova Eliska , Shah Soham , sokolowski jennifer , Park Min , Sonkusare Swapnil K
Published: September 2022

Introduction:
Transient receptor potential vanilloid 4 (TRPV4) channel is a crucial Ca
2+
influx pathway in arterial smooth muscle cells (SMCs). However, the effect of SMC TRPV4 (TRPV4
SMC
) channel activity on resting blood pressure has not been investigated.

Hypothesis:
We hypothesized that SMC TRPV4 (TRPV4
SMC
) channels regulate blood pressure under homeostatic and hypertensive conditions.

Results:
We provide first evidence that TRPV4
SMC
deletion decreases the mean arterial pressure of mice (control: 104.8 ± 2.2 mm Hg; TRPV4
SMC
-/-
: 101.4 ± 1 mm Hg). α1AR stimulation activated TRPV4
SMC
channels through protein kinase Cα (PKCα) signaling, which contributed significantly to vasoconstriction and blood pressure elevation. Surprisingly, intraluminal pressure-induced TRPV4
SMC
channel activity opposed vasoconstriction through activation of Ca
2+
-sensitive K
+
(BK) channels, indicating functionally opposite pools of TRPV4
SMC
channels. Superresolution imaging of SMCs revealed spatially separated α1AR:TRPV4 and TRPV4:BK nanodomains in SMCs. These data suggest that spatially separated α1AR-TRPV4
SMC
and intraluminal pressure-TRPV4
SMC
-BK channel signaling have opposite effects on blood pressure, with α1AR-TRPV4
SMC
signaling dominating under resting conditions. Further, in hypertensive patients and a mouse model of hypertension, constrictor α1AR-PKCα-TRPV4 signaling was upregulated, whereas dilator pressure-TRPV4-BK channel signaling was disrupted, thereby increasing vasoconstriction and elevating blood pressure.

Conclusions:
Collectively, our data identify novel smooth muscle Ca
2+
-signaling nanodomains that regulate blood pressure and demonstrate their impairment in hypertension.
Abstract P139: Association Of Thoracic Aorta Calcification And Aortic Arch Stiffness: The Multi-ethnic Study Of Atherosclerosis
Authors: Allen Tara S , Andrews Leah I , Brumback Lyndia C , Daniels Michael R , Denenberg Julie O , Thomas Isac C , Cornelissen-Guillaume Germaine G , Duprez Daniel A , Jacobs David R , Criqui Michael H , Allison Matthew A
Published: September 2022

Background:
Arterial stiffness (AS) is a robust risk factor for HTN and CVD. It remains unclear how thoracic aortic calcification (TAC) presence, volume, and density relate to AS in the aortic arch. Improved understanding of central AS may provide insight to future mechanistic approaches to prevent and control CVD.

Methods:
We evaluated 1,385 participants from MESA Exam 5 with TAC data throughout the thoracic aorta via Chest CT and pulse wave velocity (PWV) as a measure of AS across the aortic arch via MRI. We used linear regression models to assess cross-sectional associations of TAC presence, volume, and density with aortic arch PWV with adjustment for 1) age, sex, and race; and 2) age, sex, race, BMI, diabetes, estimated glomerular filtration rate, HTN-medication use, SBP, DBP, total cholesterol/high-density lipoprotein ratio, smoking status, CAC volume, CAC density, education, physical activity, and sedentary behavior.

Results:
Participants were a mean age of 69 years (SD 9) [717 (52%) female; 509 (37%) White, 359 (26%) Black, 285 (21%) Hispanic/Latino, and 232 (17%) Chinese]. Calcification was present in 1,263 (91%) and 1,228 (89%) participants in the entire thoracic aorta and aortic arch, respectively, compared to 848 (61%) and 138 (10%) in the descending and ascending aorta segments. Calcium volume in the entire thoracic aorta and aortic arch were highly correlated (r=0.94) with respective means of 866 (SD 1,724) and 564 (1,014) mm
3
. Mean PWV across the aortic arch was 9 m/sec (SD 4). After full adjustment, the presence of aortic arch calcification, compared to no aortic arch calcification, was associated with a 0.76 m/sec higher mean PWV (95% CI: 0.34 - 1.18; p<0.01), while a 1,000 mm
3
increment in aortic arch calcium volume was associated with 0.36 m/sec higher mean PWV (95% CI: 0.08-0.64; p=0.01). Results were similar when calcification in the entire thoracic aorta was the primary predictor variable. Conversely, there were no significant associations between mean or maximum calcium density measures and aortic arch PWV.

Conclusion:
TAC is highly prevalent in the thoracic aorta, especially the aortic arch. Calcification presence and higher calcification volume in the thoracic aorta, as well as the aortic arch itself, are associated with greater aortic arch AS.
Abstract P141: Phosphodiesterases Mediate The Facilitatory Effect Of Inhibitory G Proteins On Myogenic Constriction And Are Negatively Regulated By The Dual Action Of Rgs2 And 5
Authors: Dixon Alethia J , Smith Nia , Osei Owusu Patrick
Published: September 2022

G protein regulation by RGS (regulators of G protein signaling) proteins of the R4/B family plays a key role in vascular tone maintenance; However, the regulatory mechanisms are unclear. Previous studies showed that the loss of regulation of G
i/o
and G
q/11
class G proteins by RGS2 is involved in augmented myogenic tone and decreased uterine blood flow in non-pregnant mice. Additionally, RGS5, another R4/B member, was shown to regulate vascular tone by regulating G
q/11
signaling. RGS2 and 5 are structurally and functionally closely related and are co-expressed in the resistance vasculature, including the uterine vascular bed. However, whether and how RGS2 and 5 coordinate their regulatory activities to fine-tune G protein signaling and vascular tone are unknown. Here, we tested the hypothesis that the integrated activity of RGS2 and 5 decreases myogenic tone by inhibiting G
i/o
signaling, promoting cAMP-dependent smooth muscle relaxation in the uterine vascular bed. Using pressure myography, we examined myogenic constriction of uterine artery segments isolated from non-pregnant wild type,
Rgs5
KO,
Rgs2
KO, and
Rgs2/5
dbKO mice in the absence and presence of exogenous cAMP or various pharmacological inhibitors of G
i/o
signaling, while nitric oxide synthesis was continuously blocked with L-NAME. We found that myogenic constriction was reduced in
Rgs5
KO relative to WT or
Rgs2
KO arteries. Activating G
i/o
with dopamine increased, whereas cAMP decreased myogenic tone in
Rgs5
KO arteries to WT level. Dual deletion of
Rgs2
and
5
abolished the reduced myogenic tone in the absence of only
Rgs5
and enhanced dopamine induced G
i/o
effects in
Rgs2/5
dbKO arteries. Conversely, G
i/o
inhibition with pertussis toxin decreased myogenic constriction in
Rgs2/5
dbKO to similar levels in
Rgs5
KO arteries. The application of the pan-phosphodiesterase (PDE) inhibitor, IBMX, normalized myogenic tone, and blocked dopamine-mediated myogenic tone augmentation in
Rgs2
KO,
Rgs5
KO, and
Rgs2/5
dbKO arteries. We conclude that activated G
i/o
augments myogenic tone by promoting PDE-mediated inhibition of cAMP-dependent vasodilatation. While RGS2 and 5 inhibit this novel G
i/o
-PDE-cAMP signaling pathway, RGS5 dampens the inhibitory efficacy of RGS2 towards G
i/o
in uterine arteries.
Abstract P202: An Efficacy Assessment Of The Cardioprotective Effects Of Alpha-calcitonin Gene Related Peptide (αCGRP) Encapsulated Alginate Microcapsules In A Murine Model Of Heart Failure
Authors: Kumar Ambrish , Dipette Donald J , Vitello Julian , Potts Jay D
Published: September 2022

The cardioprotective role of a neuropeptide, alpha-calcitonin gene related peptide (αCGRP), has been established in a variety of cardiovascular diseases. To increase the bioavailability of the circulating peptide, we created a peptide delivery system by encapsulating αCGRP in an alginate biopolymer and showed that subcutaneous delivery of alginate-αCGRP microcapsules (αCGRP dose= 6 mg/kg/mouse) on alternate days, up to 28 days, significantly protected hearts at pathophysiological levels in a transverse aortic constriction (TAC) pressure-overload induced heart failure murine model. The present study was performed to determine if weekly subcutaneous delivery of alginate-αCGRP microcapsules exhibited similar cardioprotective effects in TAC-mice as observed in our previous study with alternate days dose delivery scheme. This study is crucial to shed light on the efficacy of these microcapsules. An electrospray method was used to prepare alginate-αCGRP microcapsules of 200 μm diameter. Male C57BL6 mice were divided into four groups (3 mice/group): i- sham, ii- sham-alginate-CGRP, iii- TAC, and iv- TAC-alginate-CGRP. Mice from TAC and TAC-alginate-CGRP groups underwent TAC procedure. Two days post-TAC, alginate-αCGRP microcapsules (αCGRP dose= 6 mg/kg/mouse) were administered subcutaneously once a week, up to 4 weeks, in the respective alginate-CGRP groups of mice. Short-axis echocardiography was performed to evaluate cardiac functions. After 28 days of microcapsules delivery, calculated percent fractional shortening (FS) and ejection fraction (EF) in mice were (in ±SD)- sham: FS= 47.6 ± 0.9, EF= 79.8 ± 0.9; sham-alginate-CGRP: FS= 47.3 ± 1.9, EF= 79.1 ± 2; TAC: FS= 34.1 ± 4.7, EF= 63.6 ± 7.1; TAC-alginate-CGRP: FS= 32.2 ± 2.3, EF= 61.0 ± 3.4. These echo data demonstrate that TAC heart failure mice had the usual significantly reduced cardiac functions, however weekly delivery of alginate-αCGRP microcapsules showed no improvement in heart performance in the TAC-mice. Combined results from our present and previous studies suggested that alginate-αCGRP microcapsules delivery on alternate days, but not weekly, is the most efficacious choice to achieve cardioprotective effects of αCGRP against pressure-induced heart failure in mice.
Abstract P211: Use Of Coaching And Technology To Improve Blood Pressure Control In Black Women With Hypertension
Authors: Abel Willie M , Efird Jimmy T
Published: September 2022

Introduction:
Hypertension (HTN) is the main cause of cardiovascular disease, especially in women. Black females (58%) are disproportionately affected by higher rates of HTN than White (41%), Hispanic (41%), and Asian (42%) females, contributing to higher death rates from myocardial infarction, heart failure, stroke, and renal failure. Active involvement in self-care is key to preventing and controlling HTN.

Aim:
To test the effects of Interactive Technology Enhanced Coaching (ITEC) on achieving blood pressure (BP) control, adherence to antihypertensive medication, and adherence to lifestyle modifications (physical activity, healthy diet, and weight management) at 3-, 6-, and 9-months post Chronic Disease Self-Management Program (CDSMP) compared with Interactive Technology (IT) alone.

Methods:
Black women in this RCT pilot study were prescribed antihypertensive medication and had BPs ≥ 130/80. All participants completed a 6-week CDSMP and afterwards were randomly assigned to the ITEC or IT group. Participants were trained to use equipment and apps that were synced to smartphones to daily monitor (over a 9-month period) BP, weight, physical activity (steps), diet (caloric intake), and medication adherence in real-time, though the Fitbit Plus Platform.

Results:
A total of 90 women were recruited. Data were analyzed from 77 participants aged 24 to 70 years. A hierarchical, mixed-effects repeated measures design was used to measure changes over time. The main effect of group means indicated no significant difference between the treatment and control groups on all study variables. The main effect of time indicated significant differences between repeated measures for SBP (
p
< .0001 and steps (
p
= .012). An interaction effect was significant for all measures except DBP and calories. SBP decreased to <130 following CDSMP and remained stable thereafter for both groups.

Conclusions:
Participant engagement declined as coaching decreased in the treatment group. Enhancing motivation and making self-care a priority in this population warrants further exploration.
Abstract P212: A Community Intervention For Hypertension Control Using Health Worker Outreach And Algorithmic Software-driven Blood Pressure Management
Authors: Deo Rahul C , Smith Rebecca , Nwoko Ogechi , McCann Gabrielle , Baker Wanda , MacRae Calum A , Price Esha , Sheffield Horace , Patel Rahul , Ortiz Elizabeth , Mayfield Stephanie , Murillo Jaime
Published: September 2022

Background:
Hypertension (HTN) in black and brown communities remains under-diagnosed and poorly controlled. Obstacles include access, lack of trust, social determinants of health (SDOH) and insufficient licensed providers. We hypothesized that a multi-faceted solution, combining screening, identification and support to address SDOH, and a remote software-driven HTN management program that shifts work to care navigators would be effective in controlling HTN.

Methods:
We launched a 500-person pilot in Detroit, MI, in March 2022. Community Health Workers (CHW) screened for patients with HTN in the community and surveyed them for SDOH. Patients received a cellular-enabled blood pressure (BP) cuff. Medications were initiated, titrated and side effects monitored according to a software-driven algorithm implementing latest HTN guidelines. Patients were contacted by a care navigator or community health worker using a combination of phone, text message, and email. Medication and testing were ordered by a licensed provider. Program success was evaluated based on proportion of patients who reached BP targets and patient satisfaction surveys.

Results:
During the initial deployment, 135 patients were screened and 86 (64%) were found to have Stage 1 HTN or greater. A total of 48 patients consented to join the program and 25 received a confirmatory BP measurement and cellular BP device. The average age of enrolled patients was 58±11 years with 52% females (N = 13), with 100% identified as Black. The median BP was 149/91mmHg, (IQR 144-159/87-98 mmHg). HTN severity on enrollment was 4% Stage 1, 59% Stage 2, and 37% Stage 3. Sixty-five % of patients were already taking one or more anti-HTN agents. A mean of 0.8 dose changes were made per patient per week. Results of the initial 250 managed patients will be presented including the percentage that reached BP goals, the number of medications required, time to reach goal, as well as impact of SDOH measures on BP control.

Conclusions:
Screening directly in an urban community resulted in a higher than expected rate of hypertension and included a high rate of stage 3 disease. A community-centered remote software-driven HTN program was feasible to implement.
Abstract P219: Effect Of Hypertension On Clinical Recovery After Stroke Thrombectomy
Authors: Killedar Amogh , Hill Michelle , Pema Peter , Budzik Ronald , Alhajeri Abdulnasser , Koss Adam , Dedhia Nikita , Loochtan Aaron , Rai Vivek , Katz Brian , Hicks William , Raetzke Brad , Vora Nirav
Published: September 2022

Title:
Effect of hypertension on clinical recovery after stroke thrombectomy

Objective:
Our goal was to identify what vascular risk factors for stroke affect outcomes after mechanical thrombectomy.

Methods:
We retrospectively reviewed stroke thrombectomy patients at our comprehensive stroke center from June 2013 to August 2016. Patients were determined to have atrial fibrillation, hypertension, diabetes, or hyperlipidemia based on historical information pre-treatment or based on hospital records during their index hospitalization. All patients in our series achieved recanalization after thrombectomy defined as a Thrombolysis in cerebral infarction (TICI) score of 2b or higher. Our endpoint was mild to moderate disability at 90 days defined by the modified Rankin Scale (mRS) score of 2 or less. We performed a univariate analysis on the above covariates affecting clinical outcome and studies all variables with a p-value of < 0.2 in a multivariate analysis to determine which independent variables affected outcome. Multi-variate analyses were performed separately for males and females.

Results:
We reviewed 288 stroke patients that underwent thrombectomy. The mean age was 69±15; NIHSS was 17±6; 36% (104 of 288) received t-PA and 42% (121 of 288) had a modified Rankin Score of
<
2. 42.7% (123 of 288) were females. From the entire group, 47.5% (137 of 288) had atrial fibrillation, 29% (83 of 288) had diabetes mellitus 68% (197 of 288) had hypertension, 38.5% (111 of 288) had hyperlipidemia and 16% (47 of 288) had a history of tobacco smoking. After considering positive univariates from above, our multivariate logistic regression model identified that not having hypertension [

OR 2.32, CI 1.01-5.41,
p=0.05

] predicted better outcome post thrombectomy procedure for males after a successful recanalization.

Conclusion:
Our analysis suggests that, for males, the odds of a positive outcome after a successful thrombectomy procedure is positively influenced when the patient is not hypertensive. No traditional risk factor appeared to influence the outcome in females. Further prospective study is required to validate these findings.