bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P175: Impairment of Autonomic Function Precedes Blood Pressure Elevation in Rat Model of Pre-eclampsia
Authors: Shaltout Hossam A , Yamaleyeva Liliya M , Bader Michael , Dechend Ralph , Brosnihan Bridget 
Published: March 2022

Hypertensive disorders of pregnancy including pre-eclampsia affect about 5-7% of all pregnant women and can cause severe acute morbidity, long-term disability and death among mothers and babies. Impairment of heart rate variability predicts risk of cardiovascular disease and all cause mortality. In this study we investigated the hypothesis that impairment of the autonomic function at early time point during pregnancy precedes and may lead to the elevation of blood pressure.
To test this hypothesis, blood pressure and heart rate were recorded under 2% isoflurane in 7 day pregnant rats generated via mating of the transgenic female rat containing the human angiotensinogen gene with the male transgenic containing human renin (hREN), the hAGTхhREN rat (TgA, n=8) which develop increased blood pressure, proteinuria and increased sensitivity to angiotensin II in the last half of gestation. The reverse mating of male containing the human angiotensinogen gene with the female transgenic containing human renin (TgR, n=8) which do not develop preeclampsia, and pregnant SD (n=8) rats at day 7 of gestation were used as controls.
By the 7th day of pregnancy, TgA rats had significantly impaired heart rate variability measured as root of mean successive differences (rMSSD) compared to SD and TgR (2.39 ±0.3 ms vs. 3.4 ± 0.2 in SD or 3.4 ±0.1 in TgR) and impaired baroreflex sensitivity measured as HF alpha (1.2±0.3 ms/mmHg vs. 2.5±0.4, SD or 1.7±0.26, TgR)
There was no difference in systolic arterial pressure or heart rate among the three groups at this time point but diastolic pressure was higher in TgA and TgR (91± 3.5 vs. 85±2.4 or vs. 75 ±2 mmHg in SD rats)
Although the predictive value of impaired baroreflex and heart rate variability in preeclampsia development needs further investigation, our findings suggest that these changes at early pregnancy precede and may contribute to the significant rise in pressure in the last half of gestation in this rat model of pre-eclampsia which may have significant clinical implications.
Abstract P185: Cardiometabolic and Inflammatory Biomarkers in the Dahl Salt-sensitive Rat
Authors: Igreja Bruno , Pires Nuno , Wright Lyndon C , Soares-da-Silva Patrício 
Published: March 2022

The Dahl salt-sensitive (Dahl/SS) rat is a genetic model of salt-sensitive hypertension that develops left ventricle (LV) hypertrophy after five to six weeks and cardiac failure with LV dilation and contractile dysfunction after 10 to 12 weeks of high-salt intake. The aim of the present study was to evalute cardiometabolic and inflammatory biomarkers in the Dahl/SS rat fed a normal-salt diet (NS-0.3% NaCl) and a high-salt diet (HS-8% NaCl).
For that purpose, eight week-old Dahl/SS rats were randomized into two groups, one group received a HS and the other a NS diet for 10 weeks. In the last week of treatment, 3 out of 10 animals from the HS diet group died. All animals from the NS diet group survived (n=8). The high-salt diet induced heart and kidney hypertrophy, as shown by higher heart/body weight (3.86±0.05 vs 2.96±0.05 mg/g, p<0.05) and kidney/body weight ratios (5.23±0.29 vs 3.41±0.06 mg/g, p<0.05), as compared to the NS diet group counterparts. Rats in the HS diet group presented proteinuria (273.1±26.8 vs 34.5±2.6 mg/day, p<0.05), hypercholesterolemia (4.45±0.23 vs 3.07±0.22 mmol/l, p<0.05), reduced levels of free fatty acids (0.23±0.02 vs 0.35±0.02 mmol/l, p<0.05) and normal levels of triglycerides in plasma (1.87±0.29 vs 1.28±0.15 mmol/l, p>0.05), as compared to animals on a NS diet. Insulin plasma levels in the HS group were lower than in the NS group (1.82±0.13 vs 4.03±0.40 ng/ml, p<0.05), though the glucose plasma levels were unchanged (162±5 vs 150±7 mg/dl, p>0.05). The plasma levels of monocyte chemoattractant protein (MCP)-1 were higher in the HS than in LS diet group (105.0±10.4 vs 67.6±2.8 pg/ml, p<0.05). A multiplex inflammatory cytokine assay was used to profile expression of 23 inflammatory mediators. The plasma levels of nine inflammatory mediators, including IL-1β, IL-4 and VEGF, were significantly increased in rats in the HS group.
In conclusion, HS diet feeding in the Dahl/SS rat deteriorate cardiometabolic and inflammatory biomarkers.
Abstract P202: Angiotensin Receptor-binding Protein ATRAP as a Possible Candidate for Therapeutic Strategy of Functionally Selective Modulation of Angiotensin Receptor Signaling
Authors: Tamura Kouichi , Wakui Hiromichi , Azushima Kengo , Uneda Kazushi , Kobayashi Ryu , Ohki Kohji , Haku Sona , Haruhara Kotaro , Kinguchi Sho , Ohsawa Masato , Maeda Akinobu , Kanaoka Tomohiko , Umemura Satoshi 
Published: March 2022

Drug discovery targeting GPCRs is no longer limited to seeking agonists or antagonists to stimulate or block cellular responses associated with a particular receptor. GPCRs are now known to support a diversity of pharmacological profiles, a concept broadly referred to as functional selectivity. Therefore, if possible, functionally selective modulation of receptor signaling may be a safer, better tolerated, and more efficacious therapeutic strategy. Recent research progress is reported in the field of functional selectivity such as receptor biased ligands, and receptor binding molecules for the therapy of cardiovascular and renal pathophysiology.
The renin-angiotensin system including plays a critical role in the regulation of cardiovascular and renal function in physiological homeostasis via activity of its effector AT1R. While exaggerated activation of AT1R promotes organ damages by BP elevation and insulin resistance via enhancement of oxidative stress, inflammation and fibrotic response, genetic total inactivation of the renin-angiotensin system components, such as angiotensinogen, renin and AT1R, reportedly results in significant hypotension and in renal morphological alteration even under baseline condition from birth, indicating that baseline AT1R signaling activity is indispensable for the maintenance of cardiovascular and renal physiology.

In the course of an investigational search for a sophisticated means to regulate AT1R signaling at local tissue sites, we have focused our analysis on the AT1R-associated protein (ATRAP;
Agtrap
gene), which is a molecule that directly binds to the carboxyl[[Unable to Display Character: &#8208;]]terminal domain of AT1R. In contrast to the classical components of the renin-angiotensin system (i.e. angiotensinogen, renin and AT1R), alteration of ATRAP expression exerts no evident effects on baseline BP and renal morphology
in vivo
such as in ATRAP-transgenic mice and ATRAP-deficient mice. However, accumulating results in these mice indicate that ATRAP exerts inhibitory effects on the exaggerated activation of tissue AT1R signaling in response to pathological stimuli, in order to protect cardiovascular and renal tissues under pathological stimuli, in spite of no influence of ATRAP on physiological AT1R signaling.
Abstract P206: Structural Analysis of Glycosyl Chain at 14th Amino Acid Of Human Angiotensinogen in Plasma
Authors: Nagata Sayaka , Tokashiki Mariko , Kitamura Kazuo 
Published: March 2022

The Renin angiotensin system (RAS) is a major regulator of body fluid balance and control of blood pressure. The protease enzyme renin secreted from kidneys cleaves speci[[Unable to Display Character: &#64257;]]cally angiotensinogen (Aogen) circulating in the blood to produce angiotensin I (Ang I). Human Aogen is a heterogeneous glycoprotein constitutively secreted by the liver. In addition, human Aogen contains four putative asparagine-linked glycosylation sites (Asn 14, 137, 271, 295) and contains four cysteines (Cys 18, 138, 232, 308), with Cys18 and Cys138 linked by a disulfide bridge. The glycosyl chains and cysteines position are very important for binding of the renin.
Big angiotensin-25 (Bang-25) is a consisting of 25 amino acids with glycosyl chain (14th amino asid) and added cysteine (18th amino acid), which we recently isolated from human urine. To compare glycosyl chain of Bang-25 and Aogen, we analyzed of structure glycosyl chain at position 14th amino acid of human Aogen in plasma.
To determine of glycosyl chain at position 14th amino acid, we performed lysyl endopeptidase digestion and reduction on human plasma Aogen. Then, Aogen after digest was purified by reverse-phase high-performance liquid chromatograpy (RP-HPLC), and glycosyl chain structure analyzed by the two-/three-dimensional HPLC mapping method.
We show that plasma Aogen has three types of glycosyl chain at position 14th amino acid. One glycosyl chain structure is identical to Bang-25 in urine. N-linked glycosylation on 14th amino acid of Aogen plays an important role about renin reaction. In addition, Bang-25 is rapidly cleaved by chymase to Ang II, but is resistant to cleave by renin. These results suggest that the structure of the glycosyl chain at position 14th amino acid of the human Aogen may be involved in the substrate specificity for renin or chymase.
Abstract P252: Effect of Maternal Diabetes on Fetal Programming of Vascular Remodeling Mechanisms in Adult Rats
Authors: Dib Abdallah , Bourreau Jennifer , Loufrani Laurent , Henrion Daniel , Fassot Celine 
Published: March 2022

Modifications of the intra-uterine environment are now recognized as an important cause of fetal stress. Leading to several responses such as loss of structure/function and pre-emptive adaptations to an adverse post-natal environment, and finally to adult diseases. It has been demonstrated that children of diabetic mothers have an increased risk of developing cardiovascular diseases (i.e. hypertension) during adulthood.
Blood vessels are able to reorganize their structure in response to physiological alteration of blood flow or pathological stimuli. Constrictive vascular remodeling is currently associated with the occurrence of cardiovascular diseases. Thus, our objective was to study vascular remodeling in case of in utero exposure to maternal diabetes. This is in order to investigate the effect of intra-uterine environment perturbations on vascular fetal programming. We have developed an animal model of rats exposed in utero to moderated maternal hyperglycemia (DMO), which developed an hypertension around 6 months of age.
We analyzed structure of elastic and resistance arteries (internal diameter, MCSA, intima-media thickness and remodeling parameters) in absence or presence of established hypertension in male DMO compared to controls (CMO) (at 3 and 18 months of age). Moreover, by in vivo sequential ligation of mesenteric arteries, we have studied vascular remodeling of resistance arteries in response to low (LF), normal (NF) or high flow (HF).
In old DMO, we did not observe any vascular remodeling induced by hypertension neither in aorta nor in mesenteric arteries. This could be related to the increase of smooth muscle cell attachments that we observed. Moreover, after 1 or 3 weeks of mesenteric arteries ligation, DMO did not exhibit any constrictive remodeling in LF although expansive remodeling in HF is maintained. Interestingly, we measured an increase of eNOS activity and GP91 in LF arteries of theses animals although transglutaminase-2 protein expression was not modified.
Our results demonstrate that in utero exposure to maternal diabetes induce modification of vascular remodeling mechanisms in adulthood. Absence of vascular response could be a pre-emptive adaptation to fetal programmed-hypertension in these animals.
Abstract 115: Primary Hyperadrenergic Postural Tachycardia Syndrome. Evidence From Sympathetic Nerve Recordings
Authors: Okamoto Luis E , Garland Emily M , Sato Kyoko , Diedrich Laura , Furlan Raffaello , Jacob Giris , Robertson David , Biaggioni Italo , Diedrich André 
Published: March 2022

Postural tachycardia syndrome (POTS) is a chronic disabling condition with excessive upright tachycardia and symptoms due to enhanced sympathetic activity in otherwise healthy young individuals. Because it is not clear if sympathetic activation is a primary phenomenon, or an appropriate compensatory response to hypovolemia, deconditioning or partial neuropathy, we analyzed resting supine muscle sympathetic nerve activity (MSNA) in 38 female POTS patients (mean±SD, age 32.1±9.1, BMI 22.7±5.4). MSNA showed a wide range of burst rate (19.7±12.1 bursts/min, range 1.2 to 54, 95% CI: 15.7 to 23.6). We compared the 1
st
and 4
th
Quartiles of 28 MSNA records (MSNA_Q1: < 7.3; MSNA_Q4: > 23.4 bursts/min) to determine if resting MSNA is related to heart rate (HR) or blood pressure (BP) responses to orthostatic challenge and the Valsalva maneuver (2-way ANOVA with post-hoc tests).

Upright HR was inappropriately high in both groups (MSNA_Q1: 120±19 vs. MSNA_Q4: 110±20 bpm, NS), but the MSNA_Q4 group had higher upright diastolic BP than MSNA_Q1 (81±12 vs. 62±8 mmHg, P<0.01). Similarly, there were no differences in HR response to the Valsalva maneuver between groups, but systolic and diastolic BP were higher during late phase 2 in MSNA_Q4 (p<0.05), and this was preceded by higher MSNA spike rate (44.3±16.3 vs. 81.2 ±25 maximal spikes/secs per beat, p<0.01) during early phase 2 of Valsalva maneuver.
The greater BP responses, but comparable HR responses, to posture and Valsalva challenges provide evidence that the subset of POTS patients with higher resting MSNA have a primary sympathetic activation. These patients might benefit from sympatholytic therapy in contrast to other POTS patients with low or absent resting MSNA.
Abstract P358: Central BP Variability is Increased in Hypertensive-related Target Organ Damage
Authors: De La Sierra Alejandro , Pareja Julia , Yun Sergi , Acosta Eva , Aiello Francesco , Oliveras Anna , Vazquez Susana , Armario Pedro , Blanch Pere , Sierra Cristina , Calero Francesca , Fernandez LLama Patricia 
Published: March 2022

Peripheral BP variability (BPV) has been found to be increased in hypertensives with target organ damage (TOD). It is unknown if central BP variability follows the same pattern. We aimed to evaluate short-term BPV in a group of hypertensive subjects classified as having or not cardiac, renal, or vascular TOD.

A total of 178 hypertensives (33% women; age 57±12) were evaluated. TOD was defined by the presence of left ventricular hypertrophy (LVH) on echocardiography, renal alterations (urinary albumin excretion >30mg/g or eGFR < 60 ml/min/1.73m
2
) or aortic stiffness (aortic pulse wave velocity > 10 m/s). BPV was estimated by 24-hour peripheral and central BP monitoring. Parameters evaluated included: night-to-day ratios (NDR), standard deviation (SD) and coefficient of variation (CV) for 24 hours, day and night, weighted standard deviation (WSD) and average real variability (ARV).

Ninety-two patients (51.7%) had TOD, distributed as follows: 66 (37.1%) had LVH, 47 (26.4%) had renal alterations, and 37 (20.8%) increased aortic stiffness. Systolic and diastolic night-to-day ratios and systolic BPV were increased in patients with TOD with respect to those without (table). No differences were observed in diastolic BPV. The increase in systolic BPV was also observed when comparing groups with or without LVH, renal damage or aortic stiffness. Brachial BPV exhibited the same increased variability as central BPV.
We conclude that the presence of hypertensive cardiac, renal or vascular organ damage is associated with increased systolic central BPV and reduced systolic and diastolic nocturnal fall in BP. Central BPV follows the same pattern as observed with peripheral BPV.
Abstract P027: Preconditioning Cardiosphere-Derived Cells by Hypoxia and Prolyl Hydroxylase Inhibitors to Induce HIF-Related Metabolic Changes and C-Kit Expression
Authors: Tan Suat Cheng , Carr Carolyn A , Yeoh Kar Kheng , Heather Lisa C , Ambrose Lucy , Schofield Chris , Clarke Kieran 
Published: March 2022

Cardiosphere-derived cells (CDCs) decrease loss of cardiac function following infarction, but the potential of CDC therapy is limited due to the low retention rate and the time required to obtain sufficient cells for transplantation.
AIM: Here, we aimed to precondition CDCs by culturing under hypoxia, or with prolyl hydroxylase inhibitors (PHIs), to prepare the cells for the hypoxic environment within the infarcted heart.
METHODS: Rat heart explants were cultured under hypoxia (2% O2) or normoxia (21% O2) to generate explant-derived cells (EDC). EDCs were isolated, cultured to form cardiosphere and expanded into monolayer CDCs. At 80% confluency, normoxic CDCs were treated with dimethyloxalyl glycine (DMOG), Ethyl 2-(2,3-dihyroxybenzamido) (KKC226) and FG-2216 for 24 h.
RESULTS: Hypoxia, 1 mM DMOG, 0.5 mM KKC226 and 30 μM FG-2216 treated CDCs showed significantly increased HIF-1α protein expression (3.9-fold, 2.6-fold, 2.1-fold and 1.5-fold, respectively) and reduced oxygen consumption (81%, 32%, 47% and 35%, respectively), compared with normoxic CDCs. Hypoxia and PHI treatment increased protein levels of GLUT-1 (6.7-fold, 3.2-fold, 4.0-fold and 2.1-fold, respectively), resulting in significant increases in glucose uptake and lactate accumulation in the culture medium, compared with controls, commensurate with increased glycolytic metabolism after hypoxia or PHI treatment. Further, hypoxia and KKC226 increased c-Kit mRNA expression 5.1-fold and 1.5-fold, respectively. qRT-PCR confirmed increased CXCR-4 mRNA in all hypoxia and PHI-treated CDCs. EDC and CDC proliferation were 1.7-fold faster under hypoxia, compared with normoxia, but did not increase with PHI treatment.
CONCLUSION: Hypoxia and PHIs stabilized and activated HIF, which induced metabolic changes in CDCs, including GLUT-1 upregulation and a switch to anaerobic glycolytic metabolism. All preconditioned cells had reduced oxygen consumption and were better adapted to survive within an hypoxic infarct scar. HIF-induced upregulation of CXCR-4 may increase the homing of these cells to the infarcted myocardium. Finally, increased proliferation and expression of the cardiac stem cell marker, c-Kit, could decrease the time required for cell expansion prior to therapy by a week.
Abstract P097: Endothelial Overexpression of
LOX-1
Decreases Arterial Thrombosis and TF Expression in Vivo
:
Role of SIRT-1 and NFκB
Authors: Akhmedov Alexander , Camici Giovani G , Stivala Simona , Holy Erik W , Breitenstein Alexander , Lohmann Christine , Beer Juerg-Hans , Matter Christian M , Luescher Thomas F 
Published: March 2022

Background

-The hallmark of the initiation of atherosclerotic lesion is foam cell formation, and oxidized LDL (OxLDL) is believed to play a key role in the initiation of the atherosclerotic process. OxLDL is internalized by several receptors, such as SR-AI/II, SR-BI, CD36, and CD68. OxLDL is also internalized by endothelial cells, but this uptake depends on receptors other than the classic scavenger receptors. In 1997, a lectin-like oxidized LDL receptor-1 (LOX-1, OLR1) was identified in bovine aortic endothelial cells. LOX-	1 is a type II membrane glycoprotein with an apparent molecular weight of 50 kDa. It has a C-terminal extracellular C-type lectin-like domain. This lectin-like domain is essential for binding to OxLDL. Binding of OxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO, which may trigger the onset of cardiovascular events or accelerate the development of atherosclerosis.

Methods and Results

- We generated endothelial-specific
LOX-1
transgenic mice using the Tie2 promoter (
LOX-1TG
). 12-week-old male
LOX-1TG
and wild-type (WT) mice were applied for carotid artery thrombosis model.
LOX-1TG
mice developed carotid artery thrombosis within a mean occlusion time of 36.96±4.83 min, while WT control mice occluded within a mean time period of 22.75±3.87 min (n=10, P < 0.05). Initial blood flow in carotid artery did not differ between both groups of mice. Decreased occlusion time was in LOX-1TG mice vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression, macrophage accumulation and aortic fatty streaks were increased, while eNOS phosphorylation and endothelial function were reduced. In endothelial cells of
LOX-1TG
mice, reactive oxygen species were increased and the transcription factors NF-κB and Oct-1 activated. In atherosclerotic

LOX-1TG/ApoE
−/−

mice,high cholesterol diet increased VCAM-1 expression, number of macrophages, T-cells as well as plaque size.

Conclusions

-Thus, our data suggest that
LOX-1
plays a protective role in the arterial thrombosis when expressed at unphysiological levels. Therefore,
LOX-1
might represent a novel therapeutic target for atherosclerosis.
Abstract P199: Placental Growth Factor Regulates Cardiac Adaptation and Hypertrophy Through a Paracrine Mechanism
Authors: Accornero Federica , Van Berlo Jop , Benard Matthew D , Carmeliet Peter , Molkentin Jeffery D 
Published: March 2022

Objective. Paracrine growth factor-mediated crosstalk between cardiac myocytes and non-myocytes in the heart is critical for programming adaptive cardiac hypertrophy in which myocyte size, capillary density, and the extracellular matrix function coordinately. Here we examined the role that placental growth factor (PGF) plays in the heart as a paracrine regulator of myocyte to non-myocyte communication and its influence on cardiac adaptation to stress stimulation using overexpressing and PGF knockout mice.
Methods and results. We identified PGF as a secreted factor that is predominantly produced in the heart during pressure overload. We studied mice with conditional post-natal PGF overexpression (PGF DTG). While these mice did not have a baseline phenotype, except increased fibrosis with aging, they responded to pressure overload stimulation induced by transverse aortic constriction (TAC) by an increase in hypertrophy (VW/BW (mg/g): 6.6 ± 0.2 for PGF DTG versus 5.6 ± 0.2 for controls; n ≥ 6 per group; p<0.01), capillary density (vessels/myocyte: 1.6 ± 0.05 for PGF DTG versus 1.4 ± 0.03 for controls; n ≥ 7 per group; p<0.01) and fibrosis. Despite a mild increase in fibrosis, cardiac function remained intact even after 12 weeks of pressure overload. On the other hand, PGF knockout mice (Pgf-/-) succumbed to heart failure within a week of pressure overload (fractional shortening (%): 20.2 ± 2.3 for Pgf-/- versus 30.4 ± 1.1 for controls; n ≥ 7 per group; p<0.01). These hearts displayed dilation and capillary rarefaction (vessels/myocyte: 1 ± 0.05 for Pgf-/- versus 1.2 ± 0.04 for controls; n ≥ 7 per group; p<0.01). Mechanistically we show that PGF has no direct effect on the cardiomyocytes but works through its direct actions on endothelial cells and fibroblasts by inducing capillary growth and fibroblasts proliferation.
Conclusion. PGF is a secreted factor that supports hypertrophy and cardiac function during pressure overload by affecting endothelial cells and fibroblasts.