bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 089: Primary Care Physician Attitudes Toward Referring Patients To A Remote Patient Monitoring Program For Hypertension
Authors: Liyanage-Don Nadia , Onyilofor Chinelo , Lopez Maria-Jose , Bryant Kelsey , Singer Jessica , West Harry , Fraser Adina , Kronish Ian
Published: September 2022

Background:
Home blood pressure monitoring (HBPM) is recommended by national hypertension (HTN) guidelines as an evidence-based approach to improve HTN control. The use of wireless BP devices that transmit data to the electronic health record (EHR) makes HBPM eligible for remote patient monitoring (RPM) billing codes. Little is known about barriers and facilitators to HTN RPM program referral.

Methods:
We implemented a HTN RPM program at two adult primary care clinics in New York City. Patients were loaned a two-way tablet and wireless BP cuff and received virtual nursing support. We conducted 1:1 semi-structured interviews with primary care physicians (PCPs) from these clinics to elucidate attitudes about the program. Barriers and facilitators were categorized according to the Theoretical Domains Framework (TDF), which includes 14 domains of behavior change helpful for guiding implementation. Interviews were conducted by video, audio-recorded, and professionally transcribed. Three study physicians (NL, IK, CO) independently coded transcripts using content analysis, coming to consensus for discrepancies.

Results:
We interviewed 13 PCPs (7 had referred patients, 6 had not), at which point saturation of ideas was reached. Most barriers and facilitators fell into the following TDF domains:
knowledge, beliefs about consequences
,
environmental context and resources
. PCPs knew the evidence supporting HBPM and were aware of the RPM program, but confusion about eligibility, ordering, and program features were barriers to referral. Most PCPs were confident in their ability to manage RPM data and felt the program increased patient engagement in care. However, some questioned whether it would improve the status quo and others worried it might increase anxiety in certain patients. Virtual nursing support and EHR integration were seen as program benefits. However, some were concerned about increased workload, interruptions, and insufficient support to manage data between visits. Reimbursement from billing was not a strong incentive to refer.

Conclusion:
Improving communication during implementation, developing workflows to minimize interruptions, and increasing support structures may be needed to promote uptake of HTN RPM programs in primary care.
Abstract 090: Cells Of The Renin Lineage Promote Kidney Regeneration Post - Release Of Ureteral Obstruction In Neonatal Mice.
Authors: Nagalakshmi Vidya K , Li Minghong , Medrano Silvia , Gomez Roberto A , Sequeira-Lopez Maria Luisa S
Published: September 2022

Renin, the rate-limiting enzyme of the renin-angiotensin system, is increased in the kidneys subjected to ureteral obstruction. We elucidated the changes and contribution of renin-producing cells (RPCs) and the cells of renin lineage (CoRL) during kidney damage and regeneration using a partial unilateral ureteral obstruction (pUUO) model in neonatal mice. Renin cells were ablated by cell-specific expression of diphtheria toxin A chain (DTA) and labeled with GFP. We compared the cell fate changes between kidneys from the wild-type (WT) and the DTA-expressing animals, using the pUUO model. The kidneys of 3W old DTA-positive

Ren1
dDTA/+
;R26R
DTA/+

and

Ren1
dCre/+
;R26R
DTA/+

genotypes were grossly normal. We observed no significant differences in the Myh11-positive renal vascular area between the WT and the DTA-positive mice (WT-3W: 1.72±0.10 % (n=6),

Ren1
dDTA/+
;R26R
DTA/+

-3W: 1.94 ±0.123 % (n=7),

Ren1
dCre/+
;R26R
DTA/+

-3W: 2.017±0.16% (n=4)). In the kidneys of the WT group, RPCs and the CoRL significantly increased at 3W post-obstruction and the distribution was similar to the sham-operated kidneys at 2W post-relief of obstruction (Renin-positive area-WT: Sham-3W: 0.57±0.02% (n=6), Obstructed-3W: 1.59±0.44% (n=4), Post-release-2W: 0.71±0.12% (n=3)). There was a significant decrease in RPCs in the DTA animals, and the reduction of RPCs and CoRL was markedly higher in

Ren1
dCre/+
;R26R
DTA/+

mice in comparison to

Ren1
dDTA/+
;R26R
DTA/+

group. Also, the DTA-positive animals did not respond to pUUO with a significant increase in renin as in the WT (Renin-positive area:

Ren1
dDTA/+
;R26R
DTA/+

Sham-3W: 0.13±0.048% (n=5), Obstructed-3W: 0.23±0.10% (n=5), Post-release-2W: 0.14±0.04% (n=9)

Ren1
dCre/+
;R26R
DTA/+

Sham: 0.010±0.004% (n=4), Obstructed: 0.07±0.004% (n=4), Post-release: 0.03±0.004% (n=3)). The renal fibrotic area and
Tgfb1
mRNA levels post-obstruction and relief of obstruction were significantly high in

Ren1
dCre/+
;R26R
DTA/+

group in comparison to

Ren1
dDTA/+
;R26R
DTA/+

genotype due to the depletion of CoRL. Thus, our current study reveals that CoRL undergoes cell fate changes in response to obstruction and the release of obstruction, and these changes play a critical role in promoting kidney regeneration post-relief of obstruction.
Abstract 097: Seasonal Travel Stressors Modulates Hypertension In Adult Female Lupus Mice
Authors: Dinh Viet , Chaudhari Sarika , Gusson Shimoura Alme Caroline , Stubbs Cassandra , Mathis Keisa W
Published: September 2022

Systemic lupus erythematosus (SLE) is an autoimmune disorder linked to chronic renal inflammation and prevalent hypertension. We use an established murine model of SLE (NZBWF1) to mechanistically link renal inflammation to the development of hypertension. SLE mice travel to our university pre-puberty (3-6 weeks), develop autoantibodies by 20 weeks, and are consistently hypertensive by 35 weeks. We observed that when mice travel in the summer, autoantibody production is higher as the mice age vs. those that travel in the winter. This association was heightened in a subset of SLE mice that traveled to our university as adults (18-19 weeks), suggesting a role of seasonal factors, travel stressors, and age in altering disease severity. It is unknown whether these seasonal and environmental stressors can also alter blood pressure and inflammatory processes. Thus, we hypothesized that travel-induced seasonal stressors exacerbate hypertension and renal inflammation in adult SLE-prone mice. Female SLE mice traveled to our university in summer or winter at 3-6 or 18-19 weeks and were implanted with carotid catheters once they reached 35 weeks to assess mean arterial pressure (MAP). Mice were then euthanized and tissues collected to monitor plasma and renal interleukin (IL)-6, a proinflammatory cytokine. No seasonal differences were found in MAP of mice that traveled pre-puberty in summer (n = 17) and winter (n = 39) (143.6 ± 3.5 vs. 140.2 ± 2.2 mmHg; p = 0.4096) nor in plasma IL-6 (26.06 ± 7.25 vs. 15.54 ± 8.622 pg/mL; p = 0.2370) or renal IL-6 (0.01156 ± 0.00603 vs. 0.01099 ± 0.00523 pg/μg; p = 0.9445). Conversely, adult SLE mice that traveled in summer had higher MAP than those that traveled in winter (136.12 ± 2.63 vs. 128.81 ± 1.55 mmHg; p = 0.0339; n = 5-7), as well as higher plasma IL-6 (723.28 ± 220.72 vs. 280.73 ± 67.99 pg/mL; p = 0.0339) and renal IL-6 (0.078956 ± 0.017192 vs. 0.023413 ± 0.003801 pg/μg; p < 0.0001). Together, our data indicate that hypertension and renal inflammation in mice subjected to travel stress as adults is seasonally dependent. Since there were no seasonal differences in hypertension in SLE mice that traveled pre-puberty, there may be a factor related to age, seasonal environmental factors, and/or timing of the stressors that is causing the detrimental effect.
Abstract 101: Association Of Snx19 With Flotillin-1 And Caveolin-1 In Its Lipid Raft Localization And Regulation Of D
1
R Endocytosis And Blood Pressure
Authors: Lee Hewang , Villar Van A , Amatya Bibhas , Polzin Jacob , Armando Ines , Asico Laureano D , Felder Robin A , Jose Pedro A
Published: September 2022

Sorting nexin 19 (SNX19), a member of the SNX-PXA-RGS-PXC subfamily of sorting nexins, plays a vital role in lipid raft microdomain localization, but its association with flotillin-1 and caveolin-1, two of the most important lipid raft components, and in particular its linkage to the endocytosis and trafficking of dopamine D1 receptor (D
1
R) have not been determined in the renal proximal tubule (RPT). In the present study, we found that SNX19 was localized with lipid rafts in human and mouse RPT cells (RPTCs), which regulated D
1
R endocytosis. In wild type (WT) mouse RPTCs, SNX19 co-localized with flotillin-1 and caveolin-1, which was increased by treatment with fenoldopam (Fen, 25 nM, 30 min, n=4), a D1-like receptor agonist but not by vehicle (Veh). The targeting of SNX19 in lipid rafts and its colocalization with flotillin-1 and caveolin-1 were attenuated by deletion of a flotillin binding domain (
EEGPGTETETGLPVS
) (ΔFlot1), a caveolin-1 binding domain (
YHTVNRRYREF
) (ΔCav1), or both domains (ΔFlot1/Cav) in mouse RPTCs. The increase in intracellular cAMP production caused by Fen was also impaired or eliminated by the deletion of either flotillin-1 or caveolin-1 or both binding domains (WT-Veh: 100±16.6%, n=3, WT-Fen: 195.3±10.6%, n=4; ΔFlot1-Veh: 93.1±11.8%, n=4, ΔFlot1-Fen: 144.8±9.4%, n=3; ΔCav1-Veh: 90.9±16.3%, n=3, ΔCav1-Fen: 106.9±11.7%, n=4; ΔFlot/Cav-Veh: 63.8±10.3%, n=4, ΔFlot/Cav-Fen: 86.5±8.1%, n=4). Fen (25 nM, 30 min, n=3) decreased the colocalization of SNX19 with microtubules without an effect on actin filaments, which was abrogated by nocodazole (10 μM, 1hr), a microtubule depolymerization inhibitor. Furthermore, the renal-selective silencing of SNX19 in C57BL/6 mice (n=3) by the renal subcapsular infusion of specific
SNX19
siRNA decreased renal sodium excretion and increased systolic blood pressure (Mock siRNA: 96.8±0.88 mmHg, n=3; SNX19 siRNA: 117.7±5.77 mmHg, n=3). In conclusion, SNX19 contains both flotillin-1 and caveolin-1 binding domains and its binding with flotillin-1 and caveolin-1 are important in SNX19-mediated D
1
R signaling, renal sodium transport, and blood pressure regulation.
Abstract 103: Il-33 Supplementation Improves Vascular Function And Maternal Hypertension In Response To Placental Ischemia
Authors: Wang Xi , Shields Corbin , Tardo Geilda , Peacock Greg , Williams Jan M , Cornelius Denise C
Published: September 2022

Preeclampsia (PE), a leading cause of maternal and fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that develops after 20 weeks of gestation. PE is characterized by chronic immune activation, endothelial dysfunction, and fetal growth restriction (FGR). Clinical studies have shown decreased IL-33 signaling in PE women. We use the Reduced Uterine Perfusion Pressure (RUPP) rat model, which mimics many characteristics of PE patients including reduced IL-33 levels, to identify the mechanisms mediating maternal hypertension and FGR in PE. We hypothesized that IL-33 supplementation would improve maternal hypertension, fetal growth, and oxidative stress (ROS) during placental ischemia in pregnant rats. We implanted intraperitoneal mini-osmotic pumps infusing recombinant rat IL-33 (1 μg/kg/day) in normal pregnant (NP) and RUPP rats from gestation day 14-19. Maternal blood pressure, fetal growth, placental and renal ROS, phosphorylated endothelial nitric-oxide synthase (
p
eNOS), and uterine artery resistance index (UARI) were assessed. MAP (mmHg) increased from 104±4 in NP to 124±7 in RUPP (p<0.05) and was significantly lowered in RUPP+IL-33 to 108±10 (p<0.05, n=6-8/group). Fetal weight was significantly increased in RUPP+ IL-33 compared to RUPP (p<0.05). Placental ROS was not different among any groups. However, renal ROS (relative light units/min/mg protein) was increased from 452±33 in NP to 676±44 in RUPP (p<0.05) and was significantly decreased to 309±61 in RUPP+IL-33 (n=4-5/group, p<0.05 vs RUPP). Placental
p
eNOS expression was 4-fold lower in RUPP vs NP (p<0.05) and 5-fold lower in RUPP+IL-33 vs NP, n=3-5/group). UARI (arbitrary units) was 0.709±0.012 in RUPP vs NP (0.585±0.025, p<0.05) and was significantly lowered to 0.577±0.025 in RUPP+IL-33 rats (p<0.05 vs RUPP, n=5-6/group). These findings demonstrate a role for IL-33 in controlling vascular function and maternal blood pressure during pregnancy independent of eNOS activation. Further studies will quantify effector immune cells and inflammatory cytokine levels in response to IL-33 supplementation during placental ischemia. These data suggest that IL-33 may have therapeutic potential in management of PE pathophysiology during pregnancy.
Abstract 105: Mitotempol Restores Endothelial Dysfunction In Placental Arterioles In Preeclampsia
Authors: Kozak Kaleigh , Derayunan Alexa , De La Pena Rosinda , Beyer Andreas M , Gutterman David D , McIntosh Jennifer
Published: September 2022

Preeclampsia (PreE) is complication of pregnancy, affecting 5% of pregnancies in the United States, and presenting a significant burden to our healthcare systems. Oxidative damage and dysfunction of the placental microcirculation has been implicated. Clinical trials of antioxidant therapies to treat PreE have failed. However, none of these studies have used targeted antioxidants. Given that vascular compromise in preeclampsia may be caused by mitochondrial dysfunction, we propose that MitoTEMPOL (MT), a mitochondrial-targeted superoxide dismutase mimetic, will restore endothelium-dependent vasodilation in human placental arterioles. Arterioles from the maternal portion of the placenta of average diameter 161.1 ± 11.1 μm were cannulated on glass micropipettes and constricted with 0.1-1.5 nM endothelin-1 and flow was generated with a pressure gradient across vessel reservoirs. Flow-mediated dilation (FMD) was measured by video-microscopy presented as % maximal diameter from baseline. Smooth muscle function was evaluated by exposure to 100 μM papaverine. Vessels from normal placentas dilated to flow by 70.2% ± 3.8% (n=11), whereas vessels from PreE placentas dilated to only 47.9% ± 5.6% (n=8, p=0.005). Exposure to 10 μM of MT for 30 minutes in the organ bath restored Pre-E vessel dilation to 80.0% ± 3.9% (n=6, p=0.0003 vs PreE). FMD in normal vessels was not affected by exposure to MT (75.9% ± 7.2%, n=4, p=0.84). Significance was evaluated by 2-way ANOVA, α = 0.05. MT restores endothelium-dependent vasodilation in PreE vessels. Further evaluation of other mitochondrial-targeted antioxidants could lead to novel therapeutic options to improve vascular function in PreE.
Abstract 109: Mitochondrial Akap1 Protein Is Required For Diet-induced Obesity, Glucose Dysregulation And Hypertension
Authors: Guo Deng-Fu , Morgan Donald A , Zhao Yuying , Merrill Ronald A , Strack Stefan , Rahmouni Kamal
Published: September 2022

Mitochondria are best known as the powerhouse of the cell playing a critical role in energy metabolism with important implications in the development of obesity, a major cause of type 2 diabetes and hypertension. A-kinase anchoring protein 1 (AKAP1) is a mitochondrial scaffold protein that promote protein kinase A (PKA)-mediated phosphorylation of Drp1(Ser637) by increasing the local concentration of PKA at the outer mitochondrial membrane. However, the role of AKAP1 in the regulation of body weight, glucose homeostasis and blood pressure is not known. We used AKAP1 deficient mice to understand the physiological significance of this protein. Male and female AKAP1
-/-
and AKAP1
+/-
mice fed normal chow exhibit normal body weight relative to littermate controls. In contrast, AKAP1
-/-
and AKAP1
+/-
mice fed high fat high/sucrose diet (HFHSD) display attenuated weight gain compared to controls (male: 39.5
+
1.7 and 42.5
+
1.6 vs 47.3
+
2.3g, and female: 29.7
+
1.3 and 29.2
+
1.8 vs 32.5
+
1.5g). This was associated with significant decreased in fat mass in AKAP1
-/-
(male:16.2
+
0.9g and female: 8.7
+
1.1g) and AKAP1
+/-
(male:15.0
+
2.5g and female: 9.2
+
1.0g) mice compared to controls (male: 21.2
+
1.7g and female: 13.9
+
1.6g) whereas lean mass was not different between the three groups. Glucose tolerance test revealed that female AKAP1
-/-
mice have improved glucose handling, and insulin tolerance test showed that insulin sensitivity is better in male AKAP1
-/-
mice than controls. Notably, blood pressure was significantly lower in HFHSD-fed male AKAP1
-/-
(systolic: 124.4
+
6 mmHg) and AKAP1
+/-
(116.4
+
3 mmHg) mice vs control mice (146.4
+
5 mmHg). These findings demonstrated the importance of AKAP1 in the development of obesity and associated diabetes and hypertension. Our data also point to mitochondria function as a potential therapeutic target for treatment of common obesity and related diseases.
Abstract 113: Statins, But Not Pcsk9 Inhibitors, Reduce The Adipokine Chemerin In Familial Hypercholesterolemia: Focus On Lipoprotein Subfractions.
Authors: Tan Lunbo , Wang Na , Zee Leonie v , Roeters van Lennep Jeanine , Mulder Monique T , Lu Xifeng , Danser A.H. Jan , Verdonk Koen
Published: September 2022

Background:
Familial hypercholesterolemia (FH) is characterized by severe elevations in circulating LDL-cholesterol, and an increase in the risk of dyslipidemia-related cardiovascular disease (CVD). Chemerin, as a newly identified adipokine, is considered as an additional risk factor for CVD. Here we investigated whether it can be modified by cholesterol-lowering therapy.

Methods:
Lipoprotein subfractions were isolated by density gradient ultracentrifugation. Lipids and chemerin concentrations were determined both before and after cholesterol lowering with either a statin (atorvastatin, simvastatin, rosuvastatin, or fluvastatin) or a PCSK9 inhibitor (PCSK9i; alirocumab or evolocumab).

Results:
At baseline chemerin levels were 113±46 (statin group) and 95±44 (PCSK9i group) ng/ml, while triglyceride (TG) levels were 1.9±1.6 and 2.6±1.7 mmol/ml, high-density lipoprotein cholesterol (HDL-c) levels were 1.3±0.4 and 1.2±0.4 mmol/ml, and low-density lipoprotein cholesterol (LDL-c) levels were 5.7±1.5 and 4.9±1.4 mmol/ml (P=ns for difference between 2 groups). Chemerin correlated positively with triglycerides (r=0.45, P<0.005) and negatively with HDL-c (r=-0.33, P<0.01). Both statins and PCSK9i reduced LDL-c (by 41 and 62%, P<0.0001), triglycerides (by 13 and 19%, P<0.01), and increased HDL-c (by 8 and 23%, P<0.01), but only statins additionally reduced chemerin (by 35%, P<0.005). The lipoprotein subfraction profile revealed that chemerin accumulated particularly in the HDL3 fraction (containing >60% of all chemerin in lipoprotein subfractions), with approximately 30% being present in the HDL2 fraction, and approximately 3% in the LDL fraction. Statins reduced HDL3-c and HDL3-TG, and the level of chemerin bound to all subfractions. PCSK9i reduced HDL3-c but did not affect HDL3-TG or the level of chemerin bound to HDL3 and HDL2.

Conclusions:
Circulating chemerin occurs in different lipoprotein subfractions, accumulating particularly in the HDL3 fraction. Statins, but not PCSK9i, lowers chemerin, possibly by interfering with its levels across lipoprotein subfractions. This may represent a novel cardiovascular protective function of statins.
Abstract 122: Effect Of Tie2-cre Endothelial Caveolin-1 Deficiency Mice On Murine Cardiovascular And Metabolic Phenotypes
Authors: Gholami Shadi K , Ranjit Sanjay , Abidin Fatty Fazzila , Trefts Elijah , Mohd Hafiz Ngoo Siti khairani , Garza Amanda , Pojoga Luminita H
Published: September 2022

In humans, caveolin-1 (cav-1) gene polymorphisms confer a metabolic syndrome (MetS) phenotype and higher aldosterone (Aldo) levels. Further, global cav-1 knock out (KO) mice recapitulate the MetS phenotype, with both cardiovascular (CV) and metabolic dysfunction. We have shown that vascular dysfunction in the cav-1 KO is dissociated from the metabolic phenotype and is mediated by an endothelial crosstalk between cav-1 and the Aldo-mineralocorticoid receptor (MR) signaling pathway. Hence, we hypothesized endothelial cav-1 deficiency in mice is a major contributor to CV (but not metabolic) dysfunction.To assess this hypothesis, we generated Tie-2 mediated endothelium-specific cav-1 KO (ECKO) and appropriate genetic wild type (WT) control mice and studied their metabolic and CV traits in response to 1) changes in dietary salt intake (0.03% (LS) vs. 1.6% Na
+
(HS)) and 2) 3-weeks of Aldo infusion (200μg/kg/day) during sodium loading. Our results showed no difference in glucose, lipids and HOMA-IR in ECKO vs. WT mice, irrespective of the dietary intervention. However, on a HS (but not a LS) diet, ECKO vs. WT mice displayed similar CV dysfunction as previously shown in the full cav-1 KO: increased Aldo levels (73.7±11.1 vs 47.8±4.7ng/dl, p<0.05) and systolic BP (116.4±1.5 vs111±1.4 mmHg, p<0.015). Further, ECKO vs. WT mice had increased cardiac MR, eNOS, PAI-1 and CD68 expression (p<0.05 for each) as well as left ventricular hypertrophy (echocardiogram, p<0.05). In addition, 3-week HS diet led to higher albuminuria (p<0.05) and kidney/body weight ratios in ECKO vs. WT (7.2±0.2 vs 6.3±0.1). Surprisingly, as compared to placebo, Aldo infusion induced significant CV and renal damage only in the WT, but not in the ECKO. However, as compared to WT, Aldo infused ECKO had increased cardiac hypertrophy (5.9±0.2 vs 5.2±0.1) and molecular markers noted above (p<0.05 for each).In conclusion, lack of endothelial cav-1 in the mouse segregated the metabolic and CV phenotypes, and the associated CV phenotype resembles that described for the global cav-1 KO. Further, the CV and renal damage in the ECKO at baseline cannot be further enhanced by Aldo infusion. These data confirm our hypothesis that endothelial cav-1 is a major player in CV but not metabolic homeostasis.
Abstract 123: Female Rats With History Of Acute Kidney Injury Develop Endothelial Dysfunction, Increased Renal Inflammation And Decreased Aldosterone During Pregnancy
Authors: Moronge Desmond , Mellott Elisabeth , Connor Gabrielle , Ayulo Victor , Gillis Ellen E , Sullivan Jennifer C , Faulkner Jessica L
Published: September 2022

Clinical data report a 3-5 fold increase in adverse pregnancy outcomes among women with prior acute kidney injury (AKI), despite clinical recovery of renal function (creatinine clearance) before pregnancy. We showed that female Sprague-Dawley (SD) rats with recovered renal function from bilateral renal ischemia-reperfusion (AKI) develop decreased creatinine clearance, increased uterine artery resistance and decreased fetal growth in pregnancy via mechanisms unknown. We tested the hypothesis that AKI prior to pregnancy induces endothelial dysfunction, renal inflammation and dysregulated renin-angiotensin aldosterone system (RAAS) activation. Female SD rats received either 45-minute AKI or sham surgery and mated after 30 days (N=9 Sham, N=10 AKI). Gestation day 1 (GD1) was identified through vaginal smear and on GD19, rats were placed in metabolic cages before sacrificed on GD20 for plasma and tissue collection. Vascular function was assessed via wire myography on 3
rd
order mesenteric arteries while renal inflammation was quantified via flow cytometry. Pre-pregnancy AKI reduced endothelial-dependent relaxation to acetylcholine (ACh) compared to sham (concentration-response, 1nM-10uM range, 2-way ANOVA, RM, *P<0.05), indicating endothelial dysfunction. LNAME incubation ablated ACh-mediated relaxation equivocally in post-AKI and sham rats, indicating AKI induces a non-NO mediated endothelial dysfunction. Renal CD3+ T cells increased (4.4±0.23 vs 2.4±0.14%Total Renal Cells, *P<0.05) while renal IL-10 decreased (3.0±0.8 vs 12.4±2.2%CD3+ T cells) in post-AKI pregnant rats compared to sham. Urinary volume/day (29.6±5 vs 18.6±2 ml/day, *P<0.05), water intake (54.7±5 vs 40.6±1 ml/day*P<0.05) and kidney weight (2.777±0.3/mg/g vs 2.4245±0.3) increased in post-AKI pregnant rats compared to sham. In addition, urinary aldosterone levels measured by ELISA decreased in post-AKI pregnant rats compared to sham (188±34 vs 312±35 pg/ml/day, *P<0.05), suggesting disruption of fluid homeostasis and RAAS by pre-pregnancy AKI. Collectively, these data indicate that AKI prior to conception induces endothelial dysfunction, increases renal inflammation and decreases RAAS activation in pregnancy.
Abstract 133: Influence Of Sex, BMI, And Skin Color On The Accuracy Of Non-Invasive Cuffless Photoplethysmography-Based Blood Pressure Measurements
Authors: Eisenkraft Arik
Published: September 2022

Introduction:
Vital signs obtained by photoplethysmography (PPG)-based devices might be influenced by subcutaneous fat and skin color. We assessed the hypothesis that a novel PPG-based wearable monitor provides accurate blood pressure (BP) measurements in ambulatory individuals, coming for a routine BP checkup.

Methods:
This was a comparison study, conducted using a PPG-based device and cuff-based BP device. Systolic BP (SBP) and diastolic BP (DBP) measurements were stratified based on sex, BMI (<25; 25≤BMI<30; 30≤ kg/m
2
), and skin color (types 1-3 and 4-6 by the Fitzpatrick scale).

Results:
A total of 1548 measurements were analyzed. Correlations of SBP and DBP between the devices among males/females were between 0.914-0.987 (p<0.001), and Bland-Altman analysis showed a bias of less than 0.5 mmHg for both sexes. Correlations of SBP and DBP between the devices among BMI groups were between 0.931-0.991 (p<0.001), and Bland-Altman analysis showed a bias of less than 1 mmHg for all. Correlations of SBP and DBP between the devices among the skin color groups were between 0.936-0.983 (p<0.001), and Bland-Altman analysis showed a bias of less than 1 mmHg for all.

Conclusions:
In conclusion, this study shows similar and high agreements between BP measurements obtained using a PPG-based noninvasive cuffless BP device and a cuff-based BP device across sex, BMI, and skin color groups.
Abstract A2: Non-canonical AT
1
R/b-arrestin2 Activation In Brain As A Regulator Of Blood Pressure
Authors: Mathieu Natalia M , Nakagawa Pablo , Brozoski Daniel T , Grobe Justin L , Sigmund Curt D
Published: September 2022

The brain renin angiotensin system (RAS) is known for its role in cardiovascular and metabolic regulation. Angiotensin II (Ang II) is the major active product of the RAS, exerting most of its physiological effects through the angiotensin type-1 receptor (AT
1
R). Canonical or G protein-mediated signaling of the AT
1
R within the brain is known to induce dipsogenic and pressor responses to Ang II stimulation. Non-canonical or β-arrestin mediated signaling is thought to counterbalance the detrimental effects of canonical signaling. However, the role of the non-canonical AT
1
R/β-arrestin pathway within the brain is understudied. Therefore, we hypothesized that β-Arrestin activation within the brain contributes to blood pressure (BP) regulation. Global β-arrestin1 (
Arrb
1) and β-arrestin2 (
Arrb
2) knockout (KO) mice were employed to evaluate BP upon treatment with 1) deoxycorticosterone acetate (DOCA)-salt and 2) Ang II. Age- and sex-matched C57BL/6J mice served as controls. First, mice were instrumented with radiotelemetry implants and BP was continuously recorded. At baseline,
Arrb2
-KO mice exhibited similar BP when compared to WT (WT=128±5.5 vs
Arrb
2-KO=131±5.4 mmHg; n=8 and 9, respectively). However. Arrb2-KO mice exhibited exacerbated responses to DOCA-salt compared to WT (WT=152±12 vs
Arrb
2-KO=163±10 mmHg; n=8 and 9, respectively; p=0.03). Second, BP was evaluated upon acute intracerebroventricular (ICV) injection of Ang II (1ug).
Arrb
-2KO mice showed a higher BP response to Ang II compared to WT (WT=143±12 vs
Arrb
2-KO=168±10 mmHg; n=5 and 6, respectively). These findings suggest that activation of β-arrestin2 might counterbalance the effects of canonical activation of the AT
1
R through G proteins. Overall, β-arrestin2 in the brain appears to protect against cardiovascular diseases since the genetic ablation of β-Arrestin2 resulted in an exacerbated BP, particularly with brain-specific injection of Ang II.
Abstract A3: Possible Differential Effects Of Angiotensin Receptor-neprilysin Inhibitor And Angiotensin Receptor Blocker Against Hypertension And Cardiorenal Injury In A Mouse Model Of Cardiorenal Syndrome
Authors: Tsukamoto Shunichiro , Wakui Hiromichi , Uehara Tatsuki , Azushima Kengo , Tamura Kouichi
Published: September 2022

Objective:
Angiotensin receptor-neprilysin inhibitors (ARNI) are potential therapeutic candidates for the treatment of cardiorenal syndrome (CRS). Although evidence is accumulating on the therapeutic effects of ARNI for heart failure and hypertension, the effects of ARNI on kidney disease or CRS are controversial. Here, we assessed the hypothesis that ARNI has poor renal protective effect beyond its antihypertensive effect, in contrast to its promised cardioprotective effect, by using the ANS [Ang II (A) + nephrectomy (N) + saline (S)] mice, which is the CRS model.

Method:
C57BL/6 mice were divided into 5 groups (N = 5-6): Control (sham operation) group, ANS (ANS + vehicle treatment) group, Val M [ANS + moderate dose of valsartan treatment (30 mg/kg/day)] group, ARNI [ANS + sacubitril/valsartan treatment (60 mg/kg/day)] group, and Val H [ANS + high dose of valsartan treatment (60 mg/kg/day)] group. Sacrifice was performed after 4 weeks, and various analyses were conducted.

Results:
ARNI, Val M, and Val H groups attenuated the elevation of blood pressure (BP) in ANS mice (BP [mean ± standard error (SEM)] [mmHg]: ANS, 164 ± 3; ARNI, 133 ± 4; Val M, 143 ±1; Val H, 129 ± 2). Regardless of the strength of the antihypertensive effect, the ARNI group was most effective in preventing the decrease in cardiac contraction and cardiac fibrosis in ANS mice. However, the ARNI group was insufficient to suppress urinary albumin excretion (UAE) (UAE [mean ± SEM] [μg]; ANS, 5351 ± 2391; ARNI, 1169 ± 700) and renal fibrosis in ANS mice. Both valsartan groups suppressed UAE in ANS mice (UAE [mean ± SEM] [μg]; Val M, 243 ± 141; Val H, 305 ± 179), as well as renal fibrosis and glomerular swelling. In addition, the results of kidney RNA sequencing analysis showed that the receptor for advanced glycation end-products (RAGE) signaling pathway was activated in the kidney of ARNI group compared with the Val M and Val H groups.

Conclusions:
The ARNI group showed better cardioprotective effects than valsartan treatment groups, but not sufficient kidney protection. These results suggested that the relationship between the antihypertensive effects and the organ protective effects of cardiorenal injury in CRS pathology may be different between angiotensin II receptor blocker (ARB) and ARNI.
Abstract P023: Risk Scoring Model For Predicting Hypertension Among Indigenous Africans: Findings From The SIREN Study
Authors: Asowata Osahon , Okekunle Akinkunmi , Akpa Onoja , Fakunle Adekunle , SARFO FRED S , Akpalu Albert , Obiako Reginald , Wahab Kolawole , Osaigbovo Godwin , Owolabi Lukman , Akinyemi Joshua , Komolafe Morenikeji , Akinyemi Rufus O , Ovbiagele Bruce , Owolabi Mayowa
Published: September 2022

Background:
Hypertension is one of the leading risk factors for cerebrovascular and cardiovascular diseases. Early identification of populations at risk of hypertension might be critical in managing hypertension, particularly in Sub-Saharan Africa, where the burden of hypertension is very high. This study aimed to develop a risk-scoring model for predicting hypertension among indigenous Africans.

Methods:
We used 4390 population-based (80% and 20% for training and validating the model, respectively) stroke-free controls from the SIREN study to develop and validate a risk-scoring model for hypertension among Africans. Fifteen risk factors were attempted to predict hypertension using multivariable logistic regression, and the beta coefficient of significant variables were weighted using a constant and standardized weighting procedure. A standardized score was generated between 0-and 100%, and the risk-score cut-off point was estimated using the receiver operating characteristics (ROC) curve, sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and the Cohen’s kappa value at P<0.05.

Results:
Standardized and constant weight was applied to eight statistically significant risk factors, and the risk-score cut-off was 56% at a maximum Cohen’s kappa value of ≥0.71. The model performance had a ROC of 93.0% (95%CI: 92.0, 94.0), sensitivity of 84.8%, specificity of 87.9%, PPV of 90.6%, and NPV of 80.8% in the training data set. The validation data set had an ROC of 91.0% (95%CI: 89.0, 93.0), sensitivity of 80.0%, specificity of 92.8%, PPV of 91.1%, and NPV of 83.5%.

Conclusion:
The risk-scoring model for hypertension in this population was robust, sturdy with high predictive accuracy, and might be promising in the timely identification of populations at risk of hypertension for early prevention and management among indigenous Africans.
Abstract P028: Ferrostatin-1 Ameliorates Cardiac Dysfunction In A Cardiomyocyte-Specific SIRTUIN 3 Knockout Mouse Model
Authors: Cantrell Aubrey C , Zeng Heng , Williams Quinesha , Chen Jian-Xiong X
Published: September 2022

Aims:
Cardiomyocyte-specific knockout of Sirtuin 3 (SIRT3cKO) in mice results in heart failure which is, at least in part, attributable to activation of the ferroptotic cell death pathway. Using a ferroptosis inhibitor ferrostatin-1 (Fer-1), we tested whether treatment with Fer-1 would ameliorate cardiac dysfunction in SIRT3cKO mice.

Methods and Results:
SIRT3cKO and SIRT3loxp (WT) mice were injected with Fer-1 (1mg/kg/day) for 14 days i.p. Echocardiographic measurements were performed at days 0, 7, and 14. Cardiac tissue was harvested on day 15 and fractionated into mitochondrial and cytosolic compartments for analysis.

Echocardiography revealed that SIRT3loxp mice have an average EF of 59.75% and an average FS of 31.81% before injection, which are not significantly altered over the course of treatment. Meanwhile, SIRT3cKO mice have severely impaired systolic function shown by reduced EF (37.53%) and FS (18.11%) compared to that of SIRT3loxp mice. These alterations are significantly improved, although not entirely normalized post-treatment, at 48.54% and 24.52%, respectively. SIRT3cKO mice also exhibit diastolic dysfunction with an increased IVCT, IVRT, MPI, and E/E’ ratio. The IVCT and MPI were significantly attenuated after treatment.

Gene expression analysis demonstrated that SIRT3cKO hearts have decreased levels of mitochondrial GPX4, TIGAR, and HIF-2α compared to WT. After Fer-1 treatment, GPX4 and TIGAR were both upregulated in SIRT3cKO mitochondria, suggesting that the TIGAR/glutathione axis may have a critical role in initiating ferroptosis. Mitochondrial HIF-2α demonstrated a trend towards increase, although insignificant. In addition, our data revealed that levels of mitochondrial aconitase were significantly elevated after Fer-1 treatment.

Conclusions:
Fer-1 treatment improves cardiac function in a time-dependent manner in SIRT3cKO mice by reducing mitochondrial ferroptosis via increased levels of TIGAR/GPX4 and aconitase. Because SIRT3cKO cardiac function is not entirely normalized after treatment, alternative pathways may be involved in the cardiac dysfunction seen in SIRT3cKO mice, and further works are warranted to elucidate the precise underlying mechanisms of heart failure due to loss of cardiomyocyte SIRT3.
Abstract P029: Variable Expression Of Integrin Subunits In The Male And Female Kidneys Suggests A Key Factor Responsible For The Higher Prevalence Of Chronic Kidney Diseases In Women
Authors: Hossain Delowar , Mia Md S , Palamuttam Riya J , Kumar Bony D , Mathew Sijo
Published: September 2022

Clinical and epidemiological studies have highlighted the sex differences in the incidence of chronic kidney diseases. However, the underlying pathological mechanisms contributing to the higher prevalence of chronic kidney disease in women are not well known. The cell’s reciprocal communication to the basement membrane is one of the important factors in maintaining kidney functions and injury responses. The cell-basement membrane communication is mediated by cell surface receptors. Integrins are heterodimeric cell surface receptors that consist of noncovalently associated α and β subunits and are the principal receptor that transduces signaling between the cell and basement membrane. This study investigated the sex difference in the expression pattern of integrin α2, α5, and integrin β1. The kidney cortex from 2 months old C57BL/6 mice (both male and female) was investigated for the expression pattern of integrin using q-RTPCR and immunoblotting. Immunoblotting shows a 35% decrease in integrin β1 protein in females (1.13±0.15) compared to males (1.73±0.36). This was further confirmed by the fold change in mRNA expression using q-RTPCR that shows significantly lower integrin β1 mRNA levels in females compared to males 1.097 ± 0.08 (male) and 0.693± 0.11(female). The expression of collagen receptor, integrin α2 did not show a significant difference in expression between males and females in immunoblotting (0.23±0.14 vs 0.78±0.35) and q-RTPCR (1.07±0.46 vs 1.36±0.47). The receptor for fibronectin, integrin α5 also did not alter between males and females by immunoblotting (1.00±0.28 vs 0.98±0.17) and q-RTPCR (1.05±0.55 vs 1.04±0.38). The cell-specific expression in kidneys is progressing using immune histochemistry and primary cell cultures. Integrin β1 KO mice developed higher fibrosis than WT mice when subjected to injury. This observed lower integrin β1 expression could be an important factor in the modification of cell microenvironment and contributes to the higher chronic kidney disease progression in women that require further investigation.
Abstract P031: Prevalence And Severity Of Chronic Kidney Disease In Haiti: Findings From A Population-based Cohort
Authors: Roberts Nicholas L , Pierre Lookens , Yan Lily D , Metz Miranda , Dade Eliezer , Severe Patrice , Rouzier Vanessa , Tummalapalli Sri L , Mcnairy Margaret
Published: September 2022

Despite the increasing role of chronic kidney disease (CKD) as a major cause of global morbidity and mortality, there is limited understanding of its prevalence and risk factors in low-income countries, including Haiti. We hypothesized the prevalence of CKD is high in urban Haiti due to high rates of uncontrolled risk factors, primarily hypertension (HTN). We evaluated the prevalence and risk factors for CKD in a population-based cohort from Haiti. Among 2426 participants ≥18 years, serum creatinine and urinary albumin and creatinine were measured at time of study enrollment. Estimated glomerular filtration rate (eGFR) was dichotomized at <60 mL/min/1.73m
2
. Albuminuria was defined as an albumin to creatinine ratio (ACR) ≥30 mg/g. CKD was defined as reduced eGFR and/or albuminuria. HTN was defined as a systolic blood pressure (BP) ≥140 mmHg, diastolic BP ≥90 mmHg, or use of antihypertensive medication. Factors associated with CKD were assessed with logistic regression. National Health and Nutrition Examination Survey (NHANES) 2015-2018 data was used for cohort comparison. Median age was 41 years (IQR 28-55), 57% of participants were female, and 69% earned <1 USD per day. All participants identified as Black Haitian. The prevalence of HTN and diabetes were 34% (814/2426) and 6% (139/2426), respectively. Age -standardized CKD prevalence was 13.5%. More participants had albuminuria (283; 11.7%) than a reduced eGFR (70; 2.9%). Of those with HTN, 25.4% (207/814) had CKD. One participant had ESRD and required dialysis. Diabetes (adjusted odds ratio (aOR) 4.1, 95% Confidence Interval (CI): 2.7 to 6.2) and HTN (aOR 2.9, CI: 2.1 to 4.2) were significantly associated with CKD after adjusting for age, sex, education, and poverty. Compared to similarly aged non-Hispanic Black adults in NHANES, Haitians had a 14-fold lower prevalence of ESRD (0.04% vs. 0.59%). In conclusion, the prevalence of CKD is high in Port-au-Prince and HTN and diabetes were the greatest associated risk factors. The prevalence of ESRD was lower than in non-Hispanic Black Americans, likely due to low dialysis capacity in Haiti. With limited treatment options for severe CKD, early community-based identification and intervention of CKD coupled with better management of HTN and diabetes is critical.
Abstract P032: Body Position And The Effects Of Active Hypertension Treatment On Orthostatic Hypotension: Results From The SYS-EUR Trial
Authors: Grobman Ben , Turkson-Ocran Ruth-Alma N , Staessen Jan , Yu Yu-Ling , Mukamal Ken J , Juraschek Stephen P
Published: September 2022

Background:
We recently demonstrated that more intensive BP treatment lowered risk of orthostatic hypotension (OH) measured with a seated-to-standing protocol. However, seated-to-standing OH assessments are less sensitive than supine-to-standing and could miss clinically relevant OH.

Objectives:
Using data from the Systolic Hypertension in Europe (SYS-EUR) trial, we examined the effect of active hypertension treatment (vs placebo) on OH based on the difference in BP from 3 body positions (supine, seated, or standing).

Methods:
SYS-EUR was a multi-center, randomized trial that enrolled adults with isolated systolic hypertension (systolic blood pressure 160-219 mmHg, diastolic blood pressure<95 mmHg). Participants underwent blood pressure measurement in three positions: supine, seated, and standing. Using differences in BP between the 3 body positions (seated minus supine, standing minus seated, and standing minus supine), we defined OH as a drop in SBP≥20 mm Hg or DBP ≥10 mm Hg.

Results:
Among 4,673 participants (mean age 70.2 ± 6.7 yrs, 66.9% female) with 43,809 BP measurements, OH was present in 6.4% of measures with supine-to-seated, 4.3% with seated-to-standing, and 9.8% with supine-to-standing protocols, respectively (
Figure
). Compared with placebo, active BP treatment was not associated with OH, ORs being 0.81 (95% CI: 0.63, 1.04) with seated-to standing, 0.96 (95% CI: 0.73, 1.26) with supine-to-seated, and 1.00 (95% CI: 0.82, 1.21) with supine-to-standing protocols.

Conclusion:
Regardless of protocol, active hypertension treatment did not increase risk of OH, reinforcing evidence that OH should not be viewed as a complication of hypertension treatment.
Abstract P040: Angiotensin II Type 1 Receptor Is Expressed In Agouti-related Peptide Neurons Of The Hypothalamic Arcuate Nucleus Within Adult Human Brain
Authors: Ritter McKenzie L , Balapattabi Kirthikaa , Lowman Allison K , Connelly Jennifer M , Coss Dylan J , LaViolette Peter S , Nakagawa Pablo , Sigmund Curt D , Morselli Lisa L , Grobe Justin L
Published: September 2022

Local paracrine versions of the renin-angiotensin (ANG) system within the brain have been implicated in aspects of cardiovascular and metabolic control, including fluid and electrolyte homeostasis, blood pressure, and energy expenditure, and these effects are often mediated via the ANG type 1 (AT1) receptor. Previous radiographic studies of human brain support ligand binding to AT1 within the hypothalamic arcuate nucleus (ARC), but its localization to individual cell types remains unresolved. Studies of rodent brain demonstrate expression of the rodent AT1 homolog AT1A within the murine ARC almost exclusively within a subset of cells that also express Agouti-related peptide (AgRP) and neuropeptide-Y (NPY). Rodent studies also demonstrate a major role for AT1A within AgRP/NPY neurons in integrative control of energy expenditure, autonomic function, and possibly blood pressure. Thus, we hypothesized that AgRP/NPY neurons of the human ARC would express AT1. ARC sections were obtained after autopsy from a 74 year old male subject diagnosed with Amyotrophic Lateral Sclerosis, body mass index of 34, with self-reported occasional use of over the counter fluticasone propionate, fexofenadine, and topical hydrocortisone. Formalin-fixed, paraffin-embedded ARC was sectioned at 4 microns. RNAscope in situ hybridization methods were used to localize mRNA for AT1 (ACDBio catalog 602841-C2) and AgRP (557451), and nuclei were visualized using DAPI. A similar 4 micron section, obtained within 12 microns of the first section, was analyzed as a negative control (AT1 control: 310043-C2, AgRP control: 310043). As expected, robust expression of AgRP was observed within the ARC (51/106 cells), but not in regions lateral to the ARC (4/114 cells). AT1 expression was observed in cells both within (49/106 cells) and outside the ARC (26/114 cells). Within the ARC, AT1 expression was detected in approximately 40% of AgRP neurons (double-positive n=21, AgRP-only n=30, AT1-only n=28, total cells n=106 in a 95,000 μm
2
region). Only a very small number of signal artifacts (AgRP 0.13; AT1 0.01 % total area) were detected in the negative control. These findings indicate that within the human ARC, and similar to rodents, AT1 is expressed within a unique subset of AgRP/NPY neurons.
Abstract P045: Endothelin Receptor Blockade Eliminates Sex-differences In Natriuresis In Rats Acclimating To A High Salt Diet
Authors: Nasci Victoria L , Almutlaq Rawan , Pollock David M , Gohar Eman
Published: September 2022

The current understanding of sodium (Na
+
) handling, which is critical for blood pressure regulation, is based on studies done primarily in male (M) subjects. Our recent studies showed that female (F) Sprague Dawley (SD) rats reach a steady state in urinary Na
+
excretion after 1 day of increasing dietary Na
+
intake while M rats take 3-5 days. RNA sequencing data suggests that renal endothelin-1 (ET-1) signaling plays an important role in this difference, however, the role of ET receptors in sex-differences in acclimation to a high salt (HS) diet is not clear. We hypothesized that ET receptors mediate the advanced natriuretic capacity of F rats, compared to M rats, during acclimation to a HS diet. To test our hypothesis, M and F SD rats were implanted with telemeters and randomly assigned to treatment with A-182086, a dual antagonist of ET receptor A and B, or vehicle. After 2-3 days of treatment, rats were placed into metabolic cages and 24-hour urine samples were collected on a normal salt (NS, 0.3% NaCl) diet and after challenging rats with a HS (4% NaCl) diet for 1 day. Treatment with the ET receptor antagonist increased serum ET-1 and mean arterial pressure (MAP) to a comparable extent in both sexes (ET-1: M; 4.17 ± 0.65
vs
0.32 ± 0.02 pg/ml P=0.0004, F; 4.94 ± 1.01
vs
0.30 ± 0.01 pg/ml P<0.0001; MAP: M; 126 ± 2
vs
116 ± 3 mmHg P<0.0001, F; 114 ± 3
vs
107 ± 3 mmHg P<0.0043). On a NS and HS diet, F rats treated with A-182086 consumed more food than corresponding M rats (NS; P=0.0377, HS; P<0.0001), whereas vehicle-treated rats have no sex-difference in food intake. In vehicle-treated rats, urinary Na
+
excretion was higher in F compared to M rats on either NS or HS diet. Interestingly, ET receptor antagonism eliminates these sex differences in natriuresis during both dietary phases. In particular, A-182086 promotes urinary Na
+
excretion in M rats fed a HS diet (65.0 ± 2.3
vs
28.2 ± 4.6 % of Na
+
intake, P=0.0004). In conclusion, ET receptor antagonism eliminates sex-differences in natriuresis on NS and day 1 of HS. In opposition to our hypothesis, ET receptor antagonism promotes HS-induced natriuresis in M rats rather than attenuating the natriuretic capacity of F rats. A better mechanistic understanding of M-F differences in natriuresis could reveal sex-specific targets for hypertension treatment.