bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 435: The Integrity of Central Blood Pressure Regulation in Conscious Patients With Hypertension and Normal Healthy Control
Authors: Al-Rawas Sami F 
Published: July 2021

Blood pressure (BP) is centrally regulated by baroreflex mechanism where a change in BP would provoke vagal and sympathetic responses to counteract the moment by moment perturbations in BP. This study investigated the integrity of central regulation of BP in patients with hypertension (HTN) in response to known and standard autonomic tests.
Beat-by-beat measurement of arterial BPs (mmHg);systolic, diastolic and mean (M), heart rate (HR) (beats/min) and indices of brainstem responses; cardiac vagal tone (CVT; arbitrary units) and cardiac sensitivity to baroreflex (CSB; ms/mmHg) were continuously monitored and recorded using the Neuroscope system (Medifit instruments Ltd, UK). Statistical analysis was performed using two tail student’s t test.
The study included total of 23 subjects; 12 hypertensive males (mean±SD; 45±14.4 years) and 11 (3 females, 8 males) controls (35.6±9.7 y). Their age difference was not significant. The table describes the cardiovascular and brainstem responses during: baseline, supine, before and to the following autonomic tests: deep breathing (DB), sitting up, standing up, isometric handgrip (IHG) and phase IIe of valsalva’s maneouvre (Val-IIe), in addition to P values for control subjects.
In conclusion, brainstem mechanism is intact in patients with HTN, however, there were variable responses during deep breathing and sitting up tests. The baseline measurement showed improper BP control and hence continuous measurement showed more reliability than office discrete readings to ensure effective BP monitoring. The adjustment of brainstem responses to antihypertensive therapy is suggested to be used as an index to monitor treatment effect.
Abstract 224: Chronic Infusion Of Angiotensin-(1-7) Alleviates Cerebral Hemorrhagic Injury Compromised By Angiotensin II
Authors: Bihl Ji C , Xiao Xiang , Zhang Cheng , Chen Shuzhen , Wang Jinju , Zhao Bin , Chen Yanfang 
Published: July 2021

Angiotensin-(1-7) [Ang-(1-7)] is a potential vascular protective peptide which counteracts the effects of Ang II. In this study, we investigated the role of Ang-(1-7) in hemorrhagic stroke. Adult male C57BL/6 mice implanted with telemetric probe for recording arterial blood pressure (BP) were divided into four minipump treatment groups: saline, Ang II, Ang II + Ang-(1-7), Ang II + Ang-(1-7) + A-779. After 2 weeks of treatment, mice were subjected to induction of hemorrhagic stroke by microinjection of
collagenase (type VII; 0.075 U in 0.5 μL) in striatum. Mice were sacrificed at twenty-four hours after ICH induction. Brains were dissected and cut into coronal slices for histological analysis of middle cerebral artery (MCA)remodeling and hemorrhagic size. The plasma levels of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1 (MCP-1) and interleukin (IL-8) were determined by ELISA and the levels of NFκB and inhibitor of kappa B (IκB) in cerebral microvasculature were determined by western blot. We found (Figure): 1) Ang II increased BP, MCA remodeling and hemorrhagic size. 2) Ang-(1-7) significantly decreased the effects of Ang II on MCA and hemorrhage without affecting the BP, which were abolished by A-779. 3) Ang-(1-7) induced a 26-32% reduction in plasma level of TNF-α, MCP-1 and IL-8 increased by Ang II. 4) Ang-(1-7) also counter-regulated Ang II-induced NFƙB up-regulation and IƙB down-regulation. In conclusion, Ang-(1-7) counteracts Ang II on vascular remodeling and hemorrhagic injury by alleviating NFκB-related inflammation.
Abstract 469: Influences of Dietary Weight Reduction on the Atrial Natriuretic Peptide System in Obese Subjects
Authors: Haufe Sven , Engeli Stefan , Lichtinghagen Ralf , Utz Wolfgang , Schulz-Menger Jeanette , Luft Friedrich C , Birkenfeld Andreas L , Jordan Jens 
Published: July 2021

In obese individuals, reduced atrial natriuretic peptide (ANP) bioavailability appears to promote arterial hypertension and type 2 diabetes likely through direct metabolic actions. Mid-regional pro-ANP is cleaved off during ANP processing, thus, serving as ANP release marker. We hypothesized that dietary weight reduction improves ANP release.
In 75 overweight and obese women and men who had lost >5% body weight during six months hypocaloric dieting (-9.1±3.8 kg), we analyzed venous mid-regional pro-ANP and natriuretic peptide receptor (NPR) expression in abdominal subcutaneous adipose tissue before and after the intervention. Participants underwent ambulatory blood pressure (ABPM) monitoring and cardiac magnetic resonance imaging.
ABPM decreased from 118±9/73±7 to 115±9/71±6 mm Hg and left ventricular mass from 92±20 to 86±19 g (p<0.05 for all). End-diastolic and end-systolic volumes remained unchanged. Mid-regional pro-ANP plasma concentrations did not respond to weight loss (before: 51±24 pmol/; after 53± 24 pmol/l) and increased similarly during exercise testing. Adipose NPR-A mRNA expression remained unchanged whereas NPR-C receptor mRNA decreased from 1.2±0.7 to 1.0±0.5 (p<0.05).
Our data suggest that dietary weight loss does not augment ANP release in overweight and obese subjects. However, weight loss could improve ANP bioavailability through decreased clearance. Possible mechanisms are reduced fat mass and reduced expression of adipose tissue ANP scavenger receptor NPR-C.
Abstract 480: ACE2 Independent Pathways of Angiotensin 1-7 Formation in the Murine Kidney
Authors: Domenig Oliver , Manzel Arndt , Stegbauer Johannes , Gurley Susan , Antlanger Marlies , Kovarik Johannes , Säemann Marcus , Linker Ralf , Poglitsch Marko 
Published: July 2021

Fluid balance, salt retention and tissue remodeling is hormonally regulated by the Renin-Angiotensin-System. The sophisticated enzyme network serially cleaves peptide hormones generating various effector hormones including the vasoconstrictor Angiotensin 1-8 and its counterbalancing downstream metabolite Angiotensin 1-7.
LC-MS/MS based analysis of kidney and plasma of ACE2 knockout mice revealed unchanged Angiotensin 1-7 concentrations compared to wild type animals pointing to alternative pathways of Angiotensin 1-7 formation and suggesting a minor role for ACE2 in the formation of Angiotensin 1-7 in vivo. Moreover, we observed a decrease in the Angiotensin 1-8/Angiotensin 1-10 ratio in ACE2KO-mice indicating a changed conversion rate from Angiotensin 1-10 to Angiotensin 1-8.
We analyzed Angiotensin 1-7 metabolism in kidney homogenates by spiking natural substrates in the absence and presence of specific enzyme inhibitors. The metabolism of ex vivo spiked Angiotensins in kidney homogenates in presence and absence of the Prolyl-Carboxypepdidase (PCP) and Prolyl-Endopeptidase (PEP) Inhibitor ZPP and the ACE2-Inhibitor MLN-4760 revealed stronger contribution of PCP and PEP to Angiotensin 1-7 formation than ACE2.
Analyzing the formation of Angiotensin 1-8 from Angiotensin 1-10 in renal cortex and medulla homogenates of WT and ACE2KO mice in the absence and presence of an ACE-Inhibitor confirmed our observations on endogenous peptide levels and the ratio between Angiotensin 1-8 and Angiotensin 1-10 in plasma, revealing a reduced ACE activity in the renal cortex of ACE2KO.
Our study raises questions concerning the relevance of renal ACE2 for the local formation of Angiotensin 1-7. Moreover, the reduced ACE expression and activity in renal cortex might be a physiologically and therefore phenotype relevant consequence of the knockdown of ACE2 in these mice. The possible crosstalk between ACE and ACE2 expression and activity might give rise to further studies addressing the underlying mechanisms and might be important for our understanding of RAS dynamics in regard to therapeutic interventions.
Abstract P135: Deletion of the Mas Receptor Aggravates Vascular Dysfunction and the Development of Atherosclerosis Through a NO-dependent Mechanism in Apolipoprotein E-deficient Mice
Authors: Yang Guang , Grave Katharina , Thieme Manuel , Hendgen-Cotta Ulrike , Rump Lars C , Stegbauer Johannes 
Published: July 2021

Recently, we have shown that chronic Ang-(1-7) treatment acting through the Mas receptor improves vascular dysfunction in atherosclerotic apolipoprotein E-deficient (apoE-KO) mice by increasing NO bioavailability. To test whether deletion of the Mas receptor aggravates atherosclerosis and to examine the underlying mechanism, we generated apoE/Mas-KO mice.
12 weeks old ApoE-KO and apoE/Mas-KO mice fed on a lipid-rich Western diet were treated via osmotic minipumps with either saline or Ang-(1-7) (82 μg/kg/h) for 6 weeks. Aortae were stained with red oil and quantified for atherosclerosis. To examine whether Ang-(1-7) modulates the development of atherosclerosis through a NO dependent mechanism, 8 weeks old apoE-KO mice treated with L-NAME (20mg/kg/d) were infused either with Ang-(1-7) or saline for 6 weeks. Tissue nitrite, a marker for NO generation was measured by HPLC.
Endothelial dependent vasodilation and atherosclerosis was significantly impaired in apoE/Mas-KO mice compared to apoE-KO (relative lesion area of the aortic arch: 38.7±3.0 vs. 25.4±2.0%; P<0.01; specific lesion area 11.7±0.9 vs. 8.1±1.0mm2 P<0.01). Moreover, nitrotyrosin and urinary 8-Isoprostane levels, both markers for oxidative stress were significantly increased in apoE/Mas-KO compared to apoE-KO mice. In contrast, chronic Ang-(1-7) treatment attenuated atherosclerotic lesion in apoE-KO (11.1±2.6% vs. 25.4±2.0, P<0.01 and 3.1±0.8mm2 vs. 8.1±1.0, P<0.01) but not in apoE/Mas-KO mice (38.7±3.0 vs. 38.0±14.2% and 11.7±0.9 vs. 11.4±5.0mm2). Additionally, aortic nitrite content was increased in Ang-(1-7) treated apoE-KO compared to untreated apoE-KO mice (180±31 vs. 311±47μM/g, P<0.05). L-NAME treatment increased blood pressure (BP) and reduced aortic nitrite content significantly compared to sham-treated apoE-KO mice. However, Ang-(1-7) treatment did not affect BP (127±3 vs. 128±3mmHg), aortic nitrite (861±16 vs. 1004±174 μM/g) content and the development of atherosclerosis in L-NAME treated apoE-KO mice.
In conclusion, our findings indicate that Ang-(1-7) improves atherosclerosis via Mas receptor activation. Moreover, these effects seems to mediated through a NO-dependent mechanism as Ang-(1-7) failed to affect atherosclerosis in L-NAME treated mice.
Abstract P160: Role of Uncoupling Protein 2 in Stroke Susceptibility of Stroke-prone Spontaneously Hypertensive Rat
Authors: Rubattu Speranza , Cotugno Maria , Bianchi Franca , Di Castro Sara , Stanzione Rosita , Busceti Carla , Marchitti Simona , Nicoletti Ferdinando , Volpe Massimo 
Published: July 2021

Mitochondrial dysfunction causes severe cellular derangements potentially underlying tissue injury and consequent diseases. Evidence of a direct involvement of mitochondrial dysfunction in hypertensive target organ damage is still poor.
The gene encoding Uncoupling Protein 2 (UCP2), a inner mitochondrial membrane protein, maps inside stroke QTL/STR1 in stroke prone spontaneously hypertensive rat (SHRSP). We explored the role of UCP2 in stroke pathogenesis of SHRSP. Male SHRSP, stroke resistant SHR (SHRSR) and reciprocal STR1/congenic rats were fed with stroke permissive Japanese style diet (JD). A group of SHRSP received JD plus fenofibrate (150 mg/kg/die). Rats were sacrificed at stroke occurrence. Additional SHRSR and SHRSP rats were sacrificed at 1, 3, 6, 12 months of age upon regular diet. SBP, BW, proteinuria, stroke signs were monitored. Brains were used for molecular analysis (UCP2 gene and protein expression, Nf-kB protein expression, oxidative stress quantification) and for histological analyses.
As a result, brain UCP2 expression was reduced to 20% by JD only in SHRSP (showing 100% stroke occurrence by 7 weeks of JD). Fenofibrate protected SHRSP from stroke and upregulated brain UCP2 (+ 100%). Congenic rats carrying STR1/QTL showed increased (+100%) brain UCP2 expression, as compared to SHRSP, when resistant to stroke, and, viceversa, decreased (-50%) brain UCP2 levels, as compared to SHRSR, when susceptible to stroke. Brain UCP2 expression progressively decreased with aging only in SHRSP, down to 15% level at one year of age (when SHRSP showed spontaneous stroke). Both brain Nf-kB expression and oxidative stress levels increased when UCP2 expression was downregulated, and viceversa. Histological analysis showed both ischemic and haemorrhagic lesions at stroke occurrence.
Our results highlight a role of UCP2 in stroke predisposition associated to hypertension in an animal model of complex human disease.
Abstract P258: Essential Hypertension Induces Early Functional and Structural Vascular Aging in Small Resistance Arteries
Authors: Virdis Agostino , Bruno Rosa Maria , Duranti Emiliano , Taddei Stefano 
Published: July 2021

We evaluated cross-sectionally whether vascular remodeling is physiologically present in normal aging, and whether hypertension causes an acceleration of the aging process for vascular function and structure.
40 essential hypertensive patients (EH, age 44.9±13.2 years; BP, 157±8/99±3 mmHg) and 36 normotensive control individuals (Ctrl, age 44.7±12.7 years; BP: 128±7/80±4 mmHg) underwent laparoscopic surgery with subcutaneous adipose tissue biopsy. Small resistance arteries were studied by pressure micromiography. Endothelium-dependent and -independent vasodilation were evaluated by dose-response curve to Acetylcholine (ACh) and sodium nitroprusside (SNP). Maximum %inhibition by L-NAME on response to Ach was calculated. Structural alterations were assessed by media-lumen ratio (M/L).
EH showed a reduced vasodilation to Ach (P<0.001), but not to SNP, compared to Ctrl. In both groups, %inhibition by L-NAME on response to ACh was inversely related to age (EH, r:-0.75; P<0.0001; Ctrl, r:-0.49; P<0.0001). NO availability was significantly reduced in EH as compared to Ctrl for each age group (<30 years: 22±6% vs 30±9%, P<0.05; 31-45 years: 17±3% vs 30±3%, P<0.0001; 46-60 years: 9±4% vs 21±6%, P60 years: 4±3% vs 13±3%, P<0.05). Age-hypertension interaction (Repeated measures ANOVA) was not significant (p= 0.25). EH showed an increased M/L (P<0.001) compared to Ctrl. In both groups, M/L was positively related to age. (EH, r:0.82; P<0.0001; Ctrl, r:0.50; P<0.0001). M/L was similar in EH and Ctrl for individuals <30 years, but greater in EH than Ctrl for the other age groups (31-45 years: 6.5±0.4% vs 5.6±0.4%, P<0.0001; 46-60 years: 7.4±0.5% vs 5.8±0.2%, P60 years: 7.9±0.3% vs 6.3±0.5%, P<0.0001). There was a significant age-hypertension interaction (Repeated measures ANOVA p= 0.0009).
In small resistance arteries, aging is characterized by progressive reduction in NO availability and increased M/L. In hypertensive patients, NO availability is early reduced in comparison to Ctrl, but the progression rate with age appears to be similar. Conversely, structural alterations are influenced by hypertension only after 30 years of age, but the progression rate with age is steeper in the presence of hypertension.
Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy
Authors: Domae Keitaro , Miyagawa Shigeru , Yoshikawa Yasushi , Fukushima Satsuki , Hata Hiroki , Saito Shunsuke , Kainuma Satoshi , Kashiyama Noriyuki , Iseoka Hiroko , Ito Emiko , Harada Akima , Takeda Maki , Sakata Yasushi , Toda Koichi , Pak Kyongsun , Yamada Tomomi , Sawa Yoshiki 
Published: July 2021

Background
Clinical effectiveness of autologous skeletal cell‐patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy.

Methods and Results

Twenty‐four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches were implanted over the surface of the left ventricle through left minithoracotomy without procedure‐related complications and lethal arrhythmia. We identified 13 responders and 11 nonresponders using the combined indicator of a major cardiac adverse event and incidence of heart failure event. In the responders, symptoms, exercise capacity, and cardiac performance were improved postoperatively (New York Heart Association class II 7 [54%] and III 6 [46%] to New York Heart Association class II 12 [92%] and I 1 [8%],
P
<0.05, 6‐minute walk test; 471 m [370–541 m] to 525 m [425–555 m],
P
<0.05, left ventricular stroke work index; 31.1 g·m
2
·beat [22.7–35.5 g·m
2
·beat] to 32.8 g·m
2
·beat [28–38.5 g·m
2
·beat],
P
=0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B‐type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B‐type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: ​OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic–area under the curve, 0.96,
P
<0.001).

Conclusions
This clinical trial demonstrated that autologous skeletal stem cell–patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility.

Registration

URL:
http://www.umin.ac.jp/english/
. Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892.
Diabetes Mellitus Is Associated With Poor In‐Hospital and Long‐Term Outcomes in Young and Midlife Stroke Survivors
Authors: MacIntosh Bradley J. , Cohen Ellen , Colby‐Milley Jessica , Fang Jiming , Zhou Limei , Ouk Michael , Wu Che‐Yuan , Shah Baiju R. , Lanctôt Krista , Herrmann Nathan , Linkewich Elizabeth , Law Marcus , Black Sandra E. , Swartz Richard H. , Kapral Moira K. , Edwards Jodi D. , Swardfager Walter 
Published: July 2021

Background
The incidence of ischemic stroke has increased among adults aged 18 to 64 years, yet little is known about relationships between specific risk factors and outcomes. This study investigates in‐hospital and long‐term outcomes in patients with stroke aged <65 years with preexisting diabetes mellitus.

Methods and Results
Consecutive patients aged <65 years admitted to comprehensive stroke centers for acute ischemic stroke between 2003 and 2013 were identified from the Ontario Stroke Registry. Multinomial logistic regression was used to estimate adjusted odds ratio (OR [95% CI]) of in‐hospital mortality or direct discharge to long‐term or continuing care. Cox proportional hazards regression was used to estimate the adjusted hazards ratio (aHR [95% CI]) of long‐term mortality, readmission for stroke/transient ischemic attack, admission to long‐term care, and incident dementia. Predefined sensitivity analyses examined stroke outcomes among young (aged 18–49 years) and midlife (aged 50–65 years) subgroups. Among 8293 stroke survivors (mean age, 53.6±8.9 years), preexisting diabetes mellitus was associated with a higher likelihood of in‐hospital death (adjusted OR, 1.46 [95% CI, 1.14–1.87]) or direct discharge to long‐term care (adjusted OR, 1.65 [95% CI, 1.07–2.54]). Among stroke survivors discharged (N=7847) and followed up over a median of 6.3 years, preexisting diabetes mellitus was associated with increased hazards of death (aHR, 1.68 [95% CI, 1.50–1.88]), admission to long‐term care (aHR, 1.57 [95% CI, 1.35–1.82]), readmission for stroke/transient ischemic attack (aHR, 1.37 [95% CI, 0.21–1.54]), and incident dementia (aHR, 1.44 [95% CI, 1.17–1.77]). Only incident dementia was not increased for young stroke survivors.

Conclusions
Focused secondary prevention and risk factor management may be needed to address poor long‐term outcomes for patients with stroke aged <65 years with preexisting diabetes mellitus.
Stroke‐Related Mortality in the United States–Mexico Border Area of the United States, 1999 to 2018
Authors: Khan Safi U. , Kalra Ankur , Yedlapati Siva H. , Dani Sourbha S. , Shapiro Michael D. , Nasir Khurram , Virani Salim S. , Michos Erin D. , Alkhouli Mohamad 
Published: July 2021

BACKGROUND
The United States (US)‐Mexico border is a socioeconomically underserved area. We sought to investigate whether stroke‐related mortality varies between the US border and nonborder counties.

METHODS AND RESULTS
We used death certificates from the Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research database to examine stroke‐related mortality in border versus nonborder counties in California, Texas, New Mexico, and Arizona. We measured average annual percent changes (AAPCs) in age‐adjusted mortality rates (AAMRs) per 100 000 between 1999 and 2018. Overall, AAMRs were higher for nonborder counties, older adults, men, and non‐Hispanic Black adults than their counterparts. Between 1999 and 2018, AAMRs reduced from 55.8 per 100 000 to 34.4 per 100 000 in the border counties (AAPC, −2.70) and 64.5 per 100 000 to 37.6 per 100 000 in nonborder counties (AAPC, −2.92). The annual percent change in AAMR initially decreased, followed by stagnation in both border and nonborder counties since 2012. The AAPC in AAMR decreased in all 4 states; however, AAMR increased in California’s border counties since 2012 (annual percent change, 3.9). The annual percent change in AAMR decreased for older adults between 1999 and 2012 for the border (−5.10) and nonborder counties (−5.01), followed by a rise in border counties and stalling in nonborder counties. Although the AAPC in AAMR decreased for both sexes, the AAPC in AAMR differed significantly for non‐Hispanic White adults in border (−2.69) and nonborder counties (−2.86). The mortality decreased consistently for all other ethnicities/races in both border and nonborder counties.

CONCLUSIONS
Stroke‐related mortality varied between the border and nonborder counties. Given the substantial public health implications, targeted interventions aimed at vulnerable populations are required to improve stroke‐related outcomes in the US‐Mexico border area.