bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARGININE METABOLISM AND ARTERIAL STIFFNESS IN HIGHLANDERS WITH HIGH ALTITUDE POLYCYTHEMIA
Authors: Li Yanan , Chen Xiaoping 
Published: May 2024

Objective:
High altitude polycythemia (HAPC) is a health condition associated with hypoxemia and erythrocytosis. Patients with chronic hypoxemia often exhibit arterial stiffness. In the advanced stages of HAPC, patients can present changes in the pulmonary circulation, but limited information exists regarding arterial stiffness. Our study aims to investigate the relationship between HAPC and arterial stiffness, and explore the underlying mechanisms.

Design and method:
At an altitude of 3500m, we conducted a study examining arterial stiffness and vascular endothelial function in two groups of hypertensive highlanders with and without HAPC, each consisting of 30 participants. Plasma samples were measured using Ultra Performance Liquid Chromatography Tandem Mass Spectroscopy.

Results:
Hypertensive highlanders with HAPC exhibited notable vascular dysfunction, as indicated by significantly impaired flow-mediated dilation (FMD) (3.97±1.21% vs. 6.82±1.46%, P < 0.001), and higher brachial-ankle pulse wave velocity (BaPWV) (1556±239 cm/s vs. 1890±459 cm/s, P < 0.001). Metabolomics analysis revealed alterations in arginine/proline metabolism and the arginine biosynthesis pathway, involving L-arginine, L-ornithine, creatine and 4-guanidinobutanoic acid. The area under the curve (AUC) values for 4 metabolites and L-arginine/L-ornithine ratio were 0.753, 0.782, 0.720, 0.717 and 0.819, respectively. Pearson correlation analysis showed that L-arginine, L-ornithine, and L-arginine/L-ornithine ratio were associated with BaPWV (r=-0.4486, P=0.00032; r=0.3400, P=0.0078; r=0.3921, P=0.0019). L-arginine, L-ornithine, 4-guanidinobutanoic acid, creatine, and L-arginine/L-ornithine ratio were correlated with FMD. Multiple linear regression analysis revealed that L-arginine and L-arginine/L-ornithine ratio were independently correlated with BaPWV (beta= -0.370, t=-3.114, P=0.003; beta=-0.268, t=-2.211, P=0.032) and FMD (beta=0.434, t=3.114, P=0.003; beta= 0.457, t=3.445, P=0.001), but L-ornithine was not independently related to BaPWV and FMD.

Conclusions:
Our study indicates that HAPC may accelerate the progression of arterial stiffness in hypertensive patients. In fact, L-arginine takes an important role in the forming of NO in vascular endothelium. So The disorder of arginine metabolism may serve as the underlying metabolic mechanism.
HIGH ESTIMATED PULSE WAVE VELOCITY IS ASSOCIATED WITH EXAGGERATED BLOOD PRESSURE RESPONSE IN YOUNG AND MIDDLE-AGED ADULTS
Authors: Huang Gang , Xu Junbo , Wang Tianbo , Liu Xiaohan , Zhang Zhen , Wu Jin 
Published: May 2024

Objective:
Estimated pulse wave velocity (ePWV) may be a simple alternative to carotid to femoral pulse wave velocity, which is currently considered as the gold-standard measure of aortic stiffness. This study aimed to investigate the relationship between ePWV and exaggerated blood pressure response (EBPR) during exercise test in young and middle-aged population.

Design and method:
This study enrolled 2,884 adults between the ages of 20-49 years from the National Health and Nutrition Examination Survey (1999-2004). ePWV was calculated by using a regression equation for age and mean blood pressure (MBP). EBPR was defined as systolic peak blood pressure >210 mmHg in men, >190 mmHg in women. Multivariate logistic regression model was constructed to explore the associations between ePWV and EBPR. The potential nonlinear correlations were explored using restricted cubic spline, and a two-piecewise logistic regression model for both sides of the a two-piecewise logistic regression model for both sides of the inflection point was constructed was conducted.

Results:
Totally, 224 (7.4%) individuals among 2,884 participants had EBPR. After adjusting for age, sex, race/ethnicity, education, smoking, drinking, physical activity, body mass index, and history of hypertension, diabetes, hyperlipidaemia and chronic kidney disease, multivariable logistic regression analysis has revealed that the risk of EBPR increased 1.3-fold (OR: 2.32,95%CI: 1.58-3.40, p<0.001) as the ePWV increased every one meter per second. Subgroup analyses have found that this association was more obviously in individuals with current drinking(OR: 2.81, 95%CI:1.87-4.24, p<0.001) or without physical activity (OR: 2.45, 95%CI:1.63-3.70, p<0.001). The restricted cubic spline has revealed a nonlinear association between ePWV and EBPR. Moreover, two-piecewise logistic regression analysis has further found that the ePWV value lower than the inflection point (<=6.04) was not associated with the increase of EBPR (OR: 3.52, 95%CI: 0.18-69.85, p=0.388). In contrast, the ePWV value higher than the inflection point (>6.04) was significantly associated with the increase of EBPR (OR: 2.35, 95%CI: 1.50-3.68, p< 0.001).

Conclusions:
Higher ePWV is positively associated with EBPR in young and middle-aged population of United States,especially in individuals with current drinking or without physical activity.
SELECTED ECHOCARDIOGRAPHIC AND BLOOD PRESSURE PARAMETERS INCLUDING VENTRICULAR-ARTERIAL COUPLING IN PREDICTING ATRIAL FIBRILLATION RECURRENCE AFTER PULMONARY VEIN ISOLATION
Authors: Gaczol Mateusz , Olszanecka Agnieszka , Bednarek Agnieszka , Kusiak Aleksander , Kielbasa Grzegorz , Moskal Pawel , Jastrzebski Marek , Sondej Tomasz , Stolarz-skrzypek Katarzyna , Rajzer Marek , Wojciechowska Wiktoria 
Published: May 2024

Objective:
Ventricular–arterial coupling (VAC) plays a pivotal role in cardiac and aortic adaptation to pathophysiological conditions. The aim of the study was to evaluate whether VAC features have an impact on the atrial fibrillation (AF) recurrence after the pulmonary vein isolation (PVI) procedure.

Design and method:
The study included patients who were admitted for elective PVI and met the following criteria: aged 40 to 75 years, without established cardiovascular diseases, with paroxysmal atrial fibrillation (AF) and sinus rhythm on admission, preserved left ventricular (LV) ejection fraction and normal carotid-femoral pulse wave velocity (PWV). Clinical and echocardiographic data were collected at baseline and follow-up visit. The following VAC parameters were analysed: arterial elastance (Ea) and left ventricular elastance (Ees) calculated as the ratio of end-systolic pressure to stroke volume and end-systolic pressure to end-systolic volume, respectively. Two-dimensional speckle tracking was used to derive left ventricular global longitudinal strain (LV GLS), and then the ratio of PWV to LV GLS was calculated.

Results:
49 patients (mean age 57.9 years) who had undergone their first PVI, after mean 13.0±2.5-month follow-up, reported engaging in more regular physical activity, experiencing EHRA class improvement (p=0.001), and using antiarrhythmic drugs less frequently (p=0.003). They had lower NT-proBNP level while blood pressure remained within normal range throughout the observation period. Following PVI, there was a decrease in LV end-diastolic (p=0.002) and end-systolic (p=0.003) volumes, as well as a decrease in left atrial volume indexed to body surface area (LAVI) (41 vs 37.6 (ml/m2); p=0.012). Additionally, there was an increase in the following: LV GLS (p=0.036), Ea (p=0.021) and Ees (p=0.002). During the study follow-up, 24.5% of patients experienced AF recurrence. In a multivariable adjusted model, only higher baseline LAVI predicts AF recurrence.

Conclusions:
Left atrial enlargement was found to be the independent predictor of PVI efficacy. Significant changes in VAC parameters at stable level of blood pressure were observed at one-year follow-up after the ablation procedure. However, further study is required to determine whether VAC is suitable for predicting the efficacy of AF ablation.
ALDOSTERONE MIGHT BE AN INITIATING FACTOR AND INTERVENTION TARGET IN AORTIC ANEURYSM AND AORTIC DISSECTION
Authors: Dang Yujie , Li Nanfang , Zhu Qing , Wu Ting , Wang Menghui , Yuan Yujuan , Zhang Xin , Shen Di , Yang Mei , Hong Jing , Zhang Delian 
Published: May 2024

Objective:
Previously, we demonstrated that aldosterone (ALD) is associated with aortic aneurysm (AA) or aortic dissection (AD). However, the underlying pathological mechanisms for ALD triggering AA or AD remain elusive. Furthermore, whether ALD antagonists are potential targeted drugs remains unclear.

Design and method:
Nine-month-old male C57BL/6J mice received ALD and salt for 4 weeks for AA/AD modeling. The ALD antagonist treatment group received spironolactone or finerenone by gavage the morning after ALD osmotic minipump implantation. Immunofluorescence and enzyme-linked immunosorbent assay were performed to evaluate ALD function in AA/AD.

Results:
The ALD-induced AA/AD specimens had significantly upregulated inflammatory markers (ICAM-1, macrophage-derived LGMN) and oxidative stress marker (ROS) levels compared to healthy aortic tissues. Furthermore, the ALD-induced AA/AD model had significantly upregulated extracellular matrix (ECM) marker (MMP-2) levels. The aortas and plasma of ALD-induced AA and AD mice had reduced vascular smooth muscle (VSMC) contractile markers (CNN1 etc). The ALD antagonist reversed this result.μ

Conclusions:
This study addressed ALD participation in the main and important pathophysiology mechanisms of AA/AD, including inflammation, oxidative stress, VSMC phenotypic transformation, and ECM degradation. ALD might be the initiating factor for AA/AD and a new intervention target.
INTERCELLULAR COMMUNICATION IN THE VASCULAR WALL THROUGH EXOSOMES: A FOCUS ON ENDOTHELIAL-SMOOTH MUSCLE INTERACTION IN HYPERTENSION
Authors: Brewster Lizzy , Perrotta Ida , Taherzadeh Zhila , Van Montfrans Gert 
Published: May 2024

Objective:
Extracellular vesicles are increasingly recognized to be central in intercellular communication, delivering messages through their content, including DNA, RNAs, proteins, and lipids, expelled particularly under cellular activation or stress. While microparticles are 100-1000 nm in size and bud of the cytoplasmic membrane, exosomes are distinct nano-sized particles (<100 nm) originating from intracellular multivesicular bodies via exocytosis. These structures are increasingly recognized to regulate biological processes including vascular repair and angiogenesis, and are seen as targets for therapeutic interventions, but their role in hypertension is little understood.
We previously showed that hypertension is associated with loss of myofibrils and migration of smooth muscle cells (SMCs) towards and across the intima of the vascular wall. Cell-to-cell communication is thought to be essential in orchestrating these functional and structural adaptions to mechano or other stresses of the vessel wall. Therefore, we analyzed the differences in exosomes in the vessel wall of resistance-sized arteries from normotensive vs hypertensive patients.

Design and method:
We assessed with transmission electron microscopy the ultrastructure of resistance-sized arteries (200-400 μm), isolated from omental samples obtained during fibroid surgery from 17 women (8 hypertensive), mean age 42 y (SE 1).

Results:
Endothelial cells (ECs) and SMCs from normotensives showed few multivesicular bodies (MVBs; (mean 0.45 (0.6) per cell) containing on average 5.0 (0.7) exosomes/MVB. The number of MVBs and exosomes progressively increased with blood pressure increase, in both ECs and SMCs, to a mean of 5 MVBs (0.9)/cell) and 8.8 (1.1) exosomes/MVB in hypertensive patients (a 20-fold increase in exosomes/cell), displaying a prominent basal (abluminal) location in ECs of hypertensives (Figure).

Conclusions:
Our study demonstrates that blood pressure increase is associated with intensified intercellular communication in resistance arteries. The increases in MVBs and exosomes at the abluminal side of the endothelium suggest a possible autocrine and paracrine role in mediating EC-to-SMC communication during vascular remodeling. Exosomes released just beneath the endothelial layer can be internalized by SMCs, transferring bioactive materials that may affect SMC phenotype and function. Our study might inform further studies on intercellular communication in the vascular wall with increasing blood pressure.
AMYLOID-BETA 40 ADVERSELY INFLUENCES LARGE ARTERY STIFFNESS AND CUTANEOUS MICROVASCULAR FUNCTION IN OLDER ADULTS WITH DIVERSE CARDIOVASCULAR RISK
Authors: Aizawa Kunihiko , Casanova Francesco , Gooding Kim M , Gates Phillip E , Strain W David , Shore Angela C , Tuharska Zofia , Meakin Paul J , Ashford Michael Lj , Khan Faisel 
Published: May 2024

Objective:
Amyloid-beta (Aβ) peptides are considered to play a prominent role in Alzheimer's disease, but emerging experimental and clinical observations link Aβ40 with adverse extracerebral vascular manifestations and cardiovascular disease events. However, it is unclear if Aβ40 adversely influences both large artery stiffness and cutaneous microvascular function in humans. We sought to determine whether Aβ40 was associated with large artery stiffness and cutaneous microvascular function in older adults with diverse cardiovascular risk.

Design and method:
This cross-sectional study analysed data from 610 older adults (65.7±8.7 yrs, 242F). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (CFPWV) using a SphygmoCor device, and cutaneous microvascular function was assessed by measuring acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) responses following iontophoresis. Plasma Aβ40 concentration was measured using a human Aβ40 assay kit (Simoa Human A β40).

Results:
One standard deviation increase in Aβ40 was significantly associated with 0.74 (0.52, 0.96) m/s greater CFPWV in an age- and sex-adjusted model (Model-1, p<0.001), which remained significant after further adjustments for conventional cardiovascular disease risk factors [Model-2, 0.46 (0.26, 0.66) m/s, p<0.001]. Additionally, one standard deviation increase in Aβ40 was significantly associated with lower cutaneous acetylcholine [-27.3 (-38.9, -15.7) au] and sodium nitroprusside [-27.0 (-38.1, -15.9) au] responses in Model-1 (both p<0.001). Further adjustments for conventional cardiovascular disease risk factors did not modify the inverse association [Model-2, acetylcholine response, -20.7 (-32.5, -8.8) au: sodium nitroprusside response, -21.1 (-32.3, -9.9) au: both p<0.001]. Subgroup analyses found an indication of interaction effect whereby female sex influenced more on the association between Aβ40 and CFPWV, and type 2 diabetes influenced more on the association between Aβ40 and cutaneous acetylcholine responses (both p<0.05).

Conclusions:
Aβ40 was associated with increased large artery stiffness and decreased cutaneous microvascular function in older adults with diverse cardiovascular risk. These findings suggest a potential mechanistic link between Aβ40 deposition in the systemic circulation and previously observed adverse cardiovascular disease outcomes.
CORRELATION BETWEEN RETINAL MICROCIRCULATION, ECHOCARDIOGRAPHIC PARAMETERS AND MYOCARDIAL CORONARY FLOW RESERVE
Authors: Rosei Claudia Agabiti , Muzi Giorgia , De Ciuceis Carolina , Bressa Stefano , Cherubini Fabio , Rossini Claudia , Petroboni Beatrice , Stassaldi Deborah , Capellini Sara , Bertacchini Fabio , Bertoli Mattia , Cerudelli Elisabetta , Salvetti Massimo , Paini Anna , Buso Giacomo , Rosei Enrico Agabiti , Bertagna Francesco , Muiesan Maria Lorenza 
Published: May 2024

Objective:
Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated the possible relationship between retinal microcirculation, positron emission tomography myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi)

Design and method:
Nineteen hypertensive patients (mean age 65 ± 11, 10 F) without flow-limiting epicardial coronary artery disease underwent patients wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera, echocardiography, including MEEi computation, and cardiac 13NH3 positron emission tomography (13NH3 PET) with assessment of myocardial coronary flow reserve (CFR). A positive 13NH3 PET was defined as a ratio of stress (regadenoson) myocardial blood flow (MBF)/mass and resting MBF/mass lower than 2.

Results:
No significant differences of demographic parameters were observed between patients with positive (n=6) vs negative (n=13) 13NH3 PET. In all patients WLR was significantly related to BMI (0,50, p=0.02), age (r=0.49, p=0.03)and LVMi (r=0.48, p=0.03) at univariate analysis. A negative correlation was also observed between WLR and total CFR (-0.64, p=0.003) and MMEi (-0.35, p=0.13). The relationship between WLR and CFR remained significant after adjustment for age and BMI (r=-0.49, p=0.047).

Conclusions:
In hypertensive patients without flow-limiting epicardial coronary artery disease, retinal WLR could reflect the presence of structural alterations in coronary microcirculation, possibly contributing to an impairment of CFR and to early LV dysfunction, as detected by low values of MEEi.
HIGH-INTENSITY INTERVAL TRAINING DOES NOT AFFECT THE EXPRESSION OF ENDOTHELIAL GENES IN SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Pacagnelli Francis , Camillo Helen Louisi , Ferreira Natália Zamberla , Freitas Ananda Brito , Carvallho Ana Paula Fleury , Okoshi Katashi , Giometti Ines Cristina , Freire Paula Paccielli , Carvalho Robson Francisco , Aguiar Andreo Fernando , Gomes Mariana Janini , Vechetti Ivan J 
Published: May 2024

Objective:
Hypertension and the aging process result in changes to the endothelial-related muscular system that may negatively impact exercise capacity. Research has shown that high-intensity interval training(HIIT) may be beneficial for individuals with hypertension.However, there are currently no studies that compare the effects of this type of exercise on endothelial markers in the skeletal muscles of aging rats.In order to examine the effects of HIIT on muscular microcirculation markers in hypertension, we assessed the genes encoding proteins related to vasomotor function (NOS3 and ET-1) and angiogenesis (VEGF and PIK3R2) in the soleus and diaphragm muscles of old spontaneously hypertensive rats. To corroborate our results, we analyzed the expression of these genes in samples from individuals who participated in HIIT for 6 weeks (GSE 109657).

Design and method:
Male 12-month-old spontaneously hypertensive rats were randomly assigned to either a sedentary group (n=10) or a high-intensity interval training (HIIT) group (n=10). The HIIT group underwent training on a rodent treadmill for 50 minutes per day, five times per week, for a period of eight weeks. Systolic blood pressure (SBP), functional capacity, and expression of endothelial gene-encoding proteins associated with NOS3, ET-1, VEGF, and PIK3R2 were analyzed. We retrieved a transcriptomic dataset (GSE109657) of human muscle biopsies collected from the vastus lateralis pre- and post-HIIT (a total of 22 samples, 11 pre-HIIT and 11 post-HIIT) for differential expression analysis. The relative expressions of NOS3, PIK3R2, VEGF were displayed through a heatmap using the MORPHEUS tool. In this dataset, ET-1 expression was not detected thus, we only represented the ET-2 transcriptional variant in the heatmap

Results:
Our findings indicated that that 8-week of HIIT led to a statistically significant reduction in SBP (p=0.001) and improvement in functional capacity (p<0.001) without affecting the expression of NOS3, PIK3R2, VEGF, or ET-1 in the soleus and diaphragm muscles. Additionally, our reanalysis of vastus lateralis muscle biopsy revealed no differences in the genes of interest, corroborating our results.

Conclusions:
These findings suggest that 8-week of HIIT may promote decreased arterial pressure and enhanced physical condition without interfering with the expression of mRNA-encoding vasomotor and angiogenic factors in different skeletal muscles.
IMPACT OF MODERATE TO VIGOROUS PHYSICAL ACTIVITY ON SYSTEMIC VASCULAR RESISTANCE IN RECENTLY DIAGNOSED TYPE 2 DIABETES: A CROSS-SECTIONAL STUDY
Authors: Olesen Thomas , Vo Son , Stidsen Jacob , Hojlund Kurt , Olsen Michael 
Published: May 2024

Objective:
To investigate if moderate to vigorous physical activity (MVPA) was negatively associated with high systemic vascular resistance (SVR) among adults with Type 2 Diabetes (T2DM). Additionally, we assessed associations between other cardiometabolic risk factors and SVR.

Design and method:
We estimated cross-sectional associations between MVPA and SVR and other selected risk factors and SVR using logistic multivariate regression models. SVR was assessed using thoracic electrical bioimpedance; high SVR was defined as 20% above normal. MVPA was calculated using accelerometer data. Insulin resistance was assessed using the Homeostasis Model Assessment 2-Insulin Resistance (HOMA2-IR). Results from adjusted analyses controlled for age, sex, MAP, BMI, HOMA2-IR, medication, and smoking are reported

Results:
The study population consisted of 824 adults (mean age = 61.6 years) with recently diagnosed T2DM (mean diabetes duration = 3.6 years). 41% were females. Median MVPA was 10.7 minutes/day, and 50.5% had high SVR.
Increments of 14.4 min/day in MVPA were independently associated with a lower risk of high SVR (OR=0.69, [0.57;0.83]). Other main determinants of high SVR were female sex (OR=2.06, [1.49;2.86]), BMI and HOMA2-IR in increments of 6.16 kg/m2(OR=2.20, [1.76;2.73]) and 1.79(OR=2.33, [1.09;4.96]), respectively. BMI had a notably greater impact on explained variability of SVR than MVPA when comparing the coefficient of determination (pseudo-R2, 35.0% vs. 7.9%).

Conclusions:
Increased levels of MVPA are associated with a reduced risk of high SVR, although BMI appears to have a more pronounced effect on SVR. MVPA could serve a dual purpose in managing both SVR and promoting weight loss in T2DM.