bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P170: Angiotensin II Receptor Associated Protein Expression Within the PVN of Spontaneously Hypertensive Rats
Authors: Aitken Andrew , Foradori Chad , Griffett Kristine , Biancardi Vinicia 
Published: October 2024

Increased levels of circulating Angiotensin II (Ang II) have been linked to the development of neurogenic hypertension and elevated sympathetic activity, primarily through the Angiotensin II Receptor 1 (AT1R). Angiotensin II Receptor Associated Protein (ATRAP) is a transmembrane protein that regulates Ang II signaling by promoting the internalization of AT1R. Studies have demonstrated that in a model of Ang II-induced hypertension, enhancing ATRAP expression in the paraventricular nucleus of the hypothalamus (PVN) via Lentivirus infection reduced high blood pressure. However, whether ATRAP is differentially expressed in Spontaneously Hypertensive Rats (SHR) is unknown.
We hypothesized that ATRAP gene and protein expression decreases during the development of hypertension in SHRs, leading to increased Ang II signaling. To test this, we used male SHRs at 4 (pre-hypertensive) and 12-weeks-old (wo, hypertensive; mean arterial pressure (MAP) 128.0±2.7 vs. 149.2±5.30 mmHg, respectively, measured by tail-cuff recording [Kent Scientific]) and age-matched normotensive Wistar rats (WIS, 92.6±3.3 vs. 123.6±4.6 mmHg, respectively). We measured ATRAP and AT1R mRNA expression in PVN samples using real-time PCR. Protein expression density of ATRAP was assessed using immunofluorescence (IF) and confocal imaging.

We found no differences in ATRAP mRNA expression in the PVN between groups (
p
>0.05). On the other hand, we found a significant increase in AT1R mRNA expression after hypertension is developed (WIS 12wo: 1.12 ± 0.35; vs. SHR 12wo: 4.17 ± 1.07,
p
=0.02). While no differences were found in ATRAP, using ATRAP/AT1R ratio as an indicator of AT1R overactivity and decrease in ratio after the development of hypertension (SHR 12wo: 0.23 ± 0.06 vs. WIS 12wo:1.05 ± 0.25) further indicate increased AngII signaling. As observed with ATRAP mRNA expression, no statistical differences were observed in ATRAP protein density within the SHR at 12wo as measured in a separate cohort of animals (MAP SHR 12wo:149.0 ± 3.7 vs. WIS 12wo:115.8 ± 4.0;
p
>0.05). These results suggest that the increased AngII signaling within the PVN of SHR are most likely due to increased AT1r expression rather than a differential expression of ATRAP. This work was partially funded by AHA 953524 to VCB.
Abstract P194: Metabolic effects of GDF15 and Activin A on trophoblasts
Authors: Hartmann Sunhild , Zucker Theresa , Botha Stefan , Schmidt-Ullrich Ruth , Secener Kerim , Stern Christina , Huppertz Berthold , Forstner Desiree , Geisberger Sabrina , Herse Florian , Gauster Martin , Ishaque Naveed , Mueller Dominik , Dechend Ralf , Nonn Olivia 
Published: October 2024

Preeclampsia (PE), a pregnancy-related complication, is a major cause of maternal and fetal morbidity and mortality. The pathophysiology is not fully elucidated.
Activin A and GDF15 are part of the TGFβ superfamily and markers for trophoblast differentiation. Both are senescence associated secretory phenotype (SASP) factors that have been associated with cardiovascular disease. Mitochondrial dysfunction is associated with SASP and both have been described in PE. Serum levels of GDF15 and Activin A, were elevated in the maternal blood prior to the onset of PE and found to be elevated in placental tissue of women with PE.
BeWo cells were metabolically reprogrammed to a physiological glucose-environment by cultivating them for 10-15 passages in a cell culture medium with 5.5 mM glucose as opposed to the standard high-glucose environment at 17.1mM. Next, BeWo cells were differentiated into multinucleated syncytiotrophoblasts with Forskolin, and with DMSO as solvent control to model cytotrophoblasts. Subsequently, these two trophoblast differentiation states were treated with GDF15 (20 ng/ml) and Activin A (20ng/ml) and the cell metabolic profile was analyzed.

Additionally, a single cell human trophoblast organoid transcriptomics dataset from Shannon et al. was investigated for expression patterns of
GDF15
and
INHBA
(Activin A) together with the overall metabolic profile of trophoblast cells.

Treating BeWo cells with Activin A and GDF15 leads to an increase in mitochondrial activity, shown by elevated ATP levels in syncytiotrophoblast and an increase in mitochondrial membrane potential in cytotrophoblasts. Additionally, the oxygen consumption rate is significantly higher in syncytiotrophoblasts after Activin A and GDF15 treatment.

In human trophoblast organoids, syncytiotrophoblasts showed the lowest metabolic activity measured by the expression of genes related to glycolysis and mitochondrial respiratory chain. Furthermore,
GDF15
and
INHBA
(Activin A) were strongly expressed in syncytiotrophoblasts.

Together, Activin A and GDF15 stimulation increases the metabolic activity in BeWo cells. As preeclampsia is associated with mitochondrial dysfunction as well as with senescence, our data indicate a potential role of Activin A and GDF15 in preeclampsia development.
Abstract P226: Sex-Dependent Effects of Perivascular Adipose Tissue on Arterial Stiffness in Hypertensive
Authors: McClintock Dillon , Bush Sydney , Sather Lisa , Tykocki Nathan , Lauver Adam , Watts Stephanie , Roccabianca Sara 
Published: October 2024

Dillon McClintock, Department of Mechanical Engineering, Michigan State University, East Lansing, MI
Sydney Bush, Department of Mechanical Engineering, Michigan State University, East Lansing, MI
Lisa Sather, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI
Nathan Tykocki, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI
Adam Lauver, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI
Stephanie W Watts, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI
Sara Roccabianca, Department of Mechanical Engineering, Michigan State University, East Lansing, MI

Perivascular adipose tissue (PVAT) plays a crucial role in arterial mechanics by significantly reducing arterial stiffness in the thoracic aorta in normotensive rats. This study aims to test the hypothesis that impact of PVAT on arterial stiffness is sex-dependent in an adiposity-driven hypertension rat model. Thoracic aorta from male and female Dahl Salt-Sensitive rats were fed control (10% fat-CD) and high-fat (60% fat-HFD) diets over 16 weeks. Uniaxial mechanical tests were then conducted on aorta samples with PVAT (+PVAT) and without PVAT (-PVAT). In -PVAT samples, arterial wall stiffness at 20% stretch (mimicking
in vivo
conditions), was higher in males compared to females on a HFD but not on a CD. HFD rats also had higher systolic blood pressures, but the increase was significant only in females. +PVAT samples’ stiffness was reduced by a 95% factor in all groups as compared to -PVAT samples. Furthermore, when including PVAT, the sex difference in the HF diet group was absent. These results suggest that PVAT has a beneficial effect that is preserved in this adiposity-driven hypertension animal model after 16 weeks on diet. Furthermore, remodeling of the arterial wall is more pronounced in male versus female rats and the inclusion of PVAT dampens this sex difference.
Abstract P227: Potential roles of vascular glucose transporter 1 in development of abdominal aortic aneurysm induced by angiotensin II
Authors: Nakayama Yuki , Torimoto Keiichi , Rizzo Victor , Eguchi Satoru 
Published: October 2024

It has been reported that pharmacological inhibition of glycolysis attenuated abdominal aortic aneurysm (AAA) development in mice. Glucose transporters (GLUTs) incorporate glucose as a first step of glycolysis. GLUT1 over-expression in vascular smooth muscle cell (VSMC) appears to enhance atherosclerosis in a mouse model. In angiotensin II (AngII) plus BAPN model of mouse AAA, silencing of VSMC AngII type 1 rec receptors attenuated AAA development and rupture which was associated with less immune cell infiltration to the aortas. However, the role of VSMC GLUT1 in AAA remains elusive. Here we tested our hypothesis that VSMC GLUT1 deletion attenuates AAA development and rupture in mice. Rat aortic VSMC were obtained by the explant method. Media glucose consumption of cultured VSMCs was evaluated in the presence or absence of angiotensin II (AngII, 100 nM) stimulation and GLUT1 inhibitor BAY-876. GLUT1 floxed mice were crossed with tamoxifen-inducible SMMHC-Cre mice. At 6 weeks of age, mice were injected with 2 mg/kg tamoxifen for 5 days. Significant vascular GLUT1 silencing was confimed with immunofluorescent chemistry. As a control, tamoxifen-treated SMMHC-Cre male mice were utilized. At 8 weeks, AngII (1 μg/kg/min) was delivered for 4 weeks. In addition, mice were received 1 mg/mL BAPN during the first 2 weeks of AngII infusion. After 4weeks, all animals were euthanized and maximal external diameter of the abdominal aorta was measured. In cultured VSMC, glucose consumption increased by AngII was attenuated by pretreatment of 100 nM BAY-876. AngII plus BAPN significantly developed AAA in control mice. However, silencing of VSMC GLUT1 did not affect AAA development by AngII plus BAPN. The survival rate due to aortic rupture in VSMC GLUT1 silenced mice and control mice treated with BAPN and AngII were 60.0% and 57.1%, respectively. AngII induced hypertension in control mice and VSMC GLUT1 silenced mice. Although GLUT1 may be a primary VSMC GLUT to enhance glucose utilization in response to AngII stimulation, VSMC GLUT1 silencing did not alter AngII-dependent AAA development or rupture in a mouse model. Since pharmacological inhibition of GLUT
attenuated AAA and associated macrophage infiltration, it is possible that GLUT1 or other GLUT expressed in macrophages may contribute to development of AAA. In conclusion, VSMC GLUT1 silencing did not alter AngII-dependent AAA development or rupture in a mouse model.
Abstract P300: Modulation of Osmolyte Levels by ACE Inhibitors and SGLT-2 Inhibitors in Normotensive Rats
Authors: Rybka Mateusz , Mazurek Lukasz , Szudzik Mateusz , Samborowska Emilia , Ufnal Marcin , Konop Marek 
Published: October 2024

Hypertension is associated with disturbances in the water-electrolyte balance, leading to changes in osmotic pressure. Osmolytes, such as taurine among other compounds, play a critical role in maintaining cellular integrity under osmotic stress.
This study evaluated the effects of ACE inhibitors (ACE-I) and SGLT-2 inhibitors (SGLT2i) on osmolyte homeostasis. Twelve-week-old male Sprague-Dawley (SD, n = 38) rats were divided into five groups: control (water), low and high doses of canagliflozin, and low and high doses of captopril. Metabolic studies were conducted in metabolic cages. Using liquid chromatography coupled with mass spectrometry (LC-MS), we measured osmolyte concentrations in blood, urine, kidney, liver and heart tissues.
The obtained results demonstrated significant increases in liver taurine concentrations (13.34 ± 1.39 vs. 10.49 ± 1.45, p=0.029) and urinary taurine excretion (25.08 ± 2.81 vs. 16.54 ± 3.77, p=0.001) in the high-dose canagliflozin group compared to controls. Both treatments enhanced the total urinary excretion of L-alanine, β-alanine, choline, glycine, taurine, and carnitine. Additionally, canagliflozin increased the excretion of betaine and glycerophosphorylcholine (GPC). A reduction in serum β-alanine was noted in the captopril-treated rats.
These findings highlight the novel effects of SGLT-2 inhibitors and ACE-I on osmolyte levels in normotensive rats, suggesting potential mechanisms contributing to their cardioprotective effects. Further research is required to elucidate the clinical significance of osmolyte changes in enhancing the protective effects of these drug classes.
Abstract P305: Resolution of Resistant Hypertension with Unilateral Adrenalectomy in Bilateral Primary Aldosteronism: A Case Report from Jordan
Authors: Al Kayed Hadeel , qussous jwana , Hajjaj Nada , Alwahedy Saba , Maaita Mahmoud , Alsuradi Awni , Tabbalat Ramzi 
Published: October 2024

Introduction:
Primary aldosteronism (PA) is a common cause of resistant hypertension. The standard of care for bilateral hyperaldosteronism is medical management, while surgery is often preferred for unilateral cases.

Case Presentation:
We report the case of a 53-year-old female with an 18-year history of hypertension. She presented with uncontrolled blood pressure despite adherence to seven antihypertensive medications.

Blood tests, including creatinine, urea, and electrolytes, were within normal limits, as was the renal ultrasound. Serum aldosterone was 136.3 pg/mL, and plasma renin activity was 0.23 ng/mL/hr, with a ratio of 593. Her antihypertensive medications were changed to hydralazine, moxonidine, and verapamil.
A Seated Saline Suppression Test performed a month later, with 2 liters of saline infused over 4 hours, showed that serum aldosterone levels failed to suppress, confirming the diagnosis of PA.
Three-Phase adrenal CT revealed a well-defined adenoma in the left adrenal gland measuring 4.5 x 3.4 cm, and a small adenoma in the right adrenal gland measuring 1.2 x 1 cm. Adrenal Vein Sampling indicated excess aldosterone secretion from both adrenal glands, confirming bilaterality.Therefore, high-dose spironolactone was added to her antihypertensive regimen; however, her BP remained elevated after 2 months of therapy.
The option of surgically removing the adrenal gland with the larger adenoma in hopes of reducing the total burden of aldosterone was discussed with the patient as the only remaining option of improving her BP control. The patient agreed and a laparoscopic left adrenalectomy was performed. Histopathological examination ruled out malignancy.
Immediate preoperative BP was 151/90 mmHg. The surgery was uneventful. All antihypertensive medications were withheld postoperatively. On the third postoperative day her BP was consistently below 130 mmHg systolic and below 85 mmHg diastolic. Her BP remained well controlled with gradual resumption of bisoprolol 5 mg/day and spironolactone 50 mg/day

Conclusion:
Despite the bilaterality of primary aldosteronism in this case, the patient's hypertension did not respond to medical treatment, necessitating surgical intervention. The unilateral adrenalectomy of the larger adenoma proved sufficient to significantly improve her persistently elevated blood pressure. This case underscores the potential efficacy of targeted surgical treatment in managing resistant hypertension associated with bilateral adrenal disease.
Abstract P313: Diastolic to Systolic Arterial stiffening has Greater Prognostic Power than Diastolic Stiffness in 20-60 Years Old Patients Undergoing 24-Hour Ambulatory Blood Pressure Monitoring
Authors: Gavish Benjamin , Bursztyn Michael , Ruilope Luis , Williams Bryan , DeLa Sierra Alejandro 
Published: October 2024

The 24-hour ambulatory pulse pressure (PP), can be expressed as a sum of two ‘PP components’: ‘elastic’ PP (elPP) and ‘stiffening’ PP (stPP) associated, respectively, with arterial stiffness at the diastolic pressure (somewhat equivalent to pulse wave velocity being measured in the diastole), and the relative stiffness change from the diastolic- to the systolic pressure. Here we assess and compare the hazard ratio (HR) of elPP and stPP for outcomes in a large cohort of young and middle-age patients.
We analyzed adequate quality 24h ambulatory blood pressure monitoring records from the Spanish Ambulatory Blood Pressure Registry. For standard deviation(SD), K=SD(SBP)/SD(DBP), elPP=PPxln(K)/(K-1) and stPP=PP-elPP. HRs were determined for age 20-40, 41-50, and 51-60 years, using Cox regression models applied to standardized elPP & stPP (combined), adjusted for age, sex, BMI, smoking status, diabetes, dyslipidemia, mean DBP, pulse rate, SD(SBP), antihypertensive treatment, and previous cardiovascular disease (CVD). The endpoints were total mortality, and death from CVD, or coronary heart disease (CHD).
Of the 24,260 patients mean age (SD) 48.0(9.0) years, 34% male] 845 deaths occurred during period of 9.6(2.2) years. The Table shows that mean elPP slightly decreased from younger to older age, while stPP strongly increased. At age 41-60 years the adjusted HRs of stPP appeared significant and greater than those of elPP for almost all cases. The most contributing adjustors in the Cox regression were smoking, for all age classes, and sex for age over 40 years.
Thus, the stiffening component may have greater predictive power than the elastic component for total mortality, and CVD&CHD death, in middle-age patients.
Abstract P330: Next-Gen Hypertension Control: Integrating Clinical Pharmacists And Cutting-Edge EPIC Electronic Medical Record For Quality And Result Driven Approaches at Federally Qualified Health Centers
Authors: Mikhataykina Maria , Agrawal Neha 
Published: October 2024

Hypertension management in Federally Qualified Health Centers (FQHCs) requires innovative and comprehensive strategies beyond traditional methods. This study explores a collaborative approach by integrating clinical pharmacists into the healthcare team and utilizing the EPIC Electronic Medical Record (EMR) system. The model addresses medical and non-medical health determinants, offering comprehensive treatment for underserved communities regardless of their ability to pay.
We hypothesized that integrating clinical pharmacists would improve and sustain blood pressure control, resulting in more patients achieving their target health outcomes. As part of multidisciplinary teams, clinical pharmacists identify, track, and analyze patient data, manage medication therapies under collaborative practice agreements, and coordinate with other healthcare providers to ensure continuous care. By leveraging EPIC EMR’s data management and patient monitoring capabilities, clinical pharmacists use real-time data to tailor medication regimens, ensure timely interventions, and conduct follow-ups every 2 to 4 weeks via telemedicine or in-clinic visits until patients reach their goals. This approach enhances patient engagement and medication adherence, which is crucial for adequate blood pressure control and cost management. It also supports personalized care addressing medical needs, lifestyle, and socioeconomic factors affecting patient health. The study, initiated in January 2024, involves adult patients with hypertension at one of the largest FQHC in Houston, TX. Key performance indicators include the percentage of patients achieving target blood pressure levels, medication adherence rates, and the frequency of follow-up visits. Preliminary data from quarter 1, 2024, shows that out of 327 patients, 58% have had at least 2 consultations with a clinical pharmacist. Out of those patients, 46% reached blood pressure control below 140/90 mmHg, while 27% showed improvement toward their goal.
This quality and result-driven approach elevates hypertension management standards, reduces health disparities, and enhances healthcare delivery within FQHCs. Clinical pharmacists have proven to be indispensable members of the healthcare team. This session aims to provide practical insights and strategies for healthcare professionals to implement similar models, paving the way for the future of hypertension care.
Abstract P404: Using Target: BP™ Initiative Resources and Awards To Improve Evidence-Based Practice Adoption And Blood Pressure Control
Authors: Smith Alison , Overton Katherine , Montgomery Liz , Yang Jianing , Wozniak Gregory , Rakotz Michael , Bolles Michele , Sanchez Eduardo 
Published: October 2024

Target:
BP™ is a national initiative created by the American Heart Association and the American Medical Association in 2017 in response to the high prevalence of uncontrolled blood pressure (BP). Committed to advancing health equity, Target: BP supports health care organizations to improve blood pressure control by leveraging AHA guidelines and scientific statements and the AMA MAP
™
framework; assists health care organizations in their journeys to improve and sustain BP control with professional education and resources; and recognizes health care organizations annually with achievement awards.

Target:
BP recognizes organizations that commit to improvement, adopt evidence-based BP activities, and achieve BP control rates ≥70 percent, currently defined as SBP<140 and DBP<90 mmHg in CMS Controlling High Blood Pressure #236. Evidence-based BP activities include 1) calibrating BP measurement devices, 2) checking to see if devices are validated, 3) training and, 4) testing care team members in BP measurement every 6-12 months, 5) using a protocol to measure and confirm BP measurements, and 6) posting a positioning graphic (job aid) next to every place where BP is measured.

Since adding evidence-based activity award criteria, self-attested achievement levels have improved from 2021 to 2023 for device calibration from 47.9% to 65.3%, for team training from 67.6% to 85.5%, for team testing from 67.0% to 86.2%, for measurement protocol use from 83.3% to 94.4%, and for job-aid posting from 54.8% to 69.6%. For each activity, Target: BP provides no-cost education and resources to help achieve the criteria. Overall participation has grown from 330 to 1806 organizations since 2017, now caring for 8.6 million patients with hypertension. In 2023, 866 organizations reported BP control rates ≥70 percent and 1489 reported the adoption of ≥4 of 6 evidence-based BP activities.
Future expansion of the evidenced-based activity criteria will address treatment intensification, lifestyle risk factors, self-measured blood pressure monitoring, and equitable health outcomes. In a 2023 survey of participating organizations, 85.2% of 230 respondents reported “improving patient outcomes” as their primary reason for participating in Target: BP. Among respondents, 95.7% agree or strongly agree that expanded criteria will help to focus QI priorities.
Award incentives appear to play a positive role in encouraging organizations to adopt evidence-based practices and improve blood pressure control.