bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Ovarian Hormone Deprivation Increases Cardiac Contractility in Old Female Rats‐ Role of Physical Training
Authors: Souza Hugo Celso Dutra , Felix Ana Carolina Sanches , Philbois Stella Vieira , Facioli Tábata Paula 
Published: June 2021

Physiological menopause occurs around 51 years of age. However, in some cases, menopause can happen early, that is, before the age of 40. Of the main consequences of early ovarian hormones deprivation or early menopause, one of the most alarming is the increased risk of cardiovascular diseases, contributing to an increase in the morbidity and mortality rate in these women. Our hypothesis is that early deprivation of ovarian hormones, when associated with the aging process, promotes more adverse cardiac remodeling and greater damage to cardiac function related to physiological ovarian failure. Thus, aerobic physical training is fundamental to attenuate these deleterious effects.PURPOSEThe objective of the present study was to investigate the effects of early deprivation of ovarian hormones on cardiac morphological and functional parameters in 82 week‐old female rats subjected to ovariectomy at 10 weeks of age, as well as to evaluate the application of aerobic training as a non‐pharmacological therapeutic tool.METHODSFemale Wistar rats (N = 48) were divided into two groups, at 10 weeks of life: early ovarian hormones deprivation by ovariectomy (OVX; N=24) and sham (SHAM; N=24). Between weeks 62 and 82, 12 animals of each group underwent aerobic training (OVX‐T and SHAM‐T, N=12). At the end of week 82, all were evaluated by echocardiography, cardiac function (Langendorff technique) and cardiac β‐adrenergic receptor expression quantification.RESULTSEchocardiography showed slight changes in morphology between OVX and SHAM. OVX (D= 101 ± 4.7 mmHg) showed higher values for maximal left intraventricular pressure in response to dobutamine, when compared to SHAM (D= 55 ± 11.8 mmHg). Both OVX‐T (D= 70 ± 4.0 mmHg) and SHAM‐T (D= 22 ± 6.6 mmHg) showed a reduction in this response. While, β‐adrenergic receptor expression was not different between the sedentary groups, SHAM‐T (0.23 ± 0.02 AU) and OVX‐T (0.29 ± 0.01AU) showed decreased expression of these receptors when compared to their respectively sedentary groups.CONCLUSIONEarly ovarian hormones deprivation associated with aging, promotes discrete changes in cardiac morphology, increasing cardiac contractility. Aerobic training decreases β‐adrenergic receptors expression, influencing the cardiac contractility.Support or Funding InformationSupported by FAPESP Grant 01937‐9This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aldosterone mediates angiotensin II‐induced myocardial fibrosis and hypertrophy via steroidogenic acute regulatory protein and aldosterone synthase
Authors: Wang Ning‐Ping , Zhang Wei‐Wei , Zheng Rong‐Hua , Bai Feng , Sturdivant Katelyn , James Erskine A , Bose Himangshu , Zhao Zhi‐Qing 
Published: June 2021

ObjectiveAldosterone produced in the adrenal glands through angiotensin II (Ang II) is known to elicit myocardial fibrosis and hypertrophy. The purpose of this study was designed to test the hypothesis that Ang II causes cardiac morphological changes through the steroidogenic acute regulatory protein (StAR)/aldosterone synthase (AS)‐dependent aldosterone synthesis primarily initiated in the heart.MethodsSprague‐Dawley rats were observed for a 28‐day period and randomized to the following groups: untreated Ang II infusion with osmotic pumps (500 ng/kg/min), dietary Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day), dietary aldosterone receptor blocker, spironolactone (100 mg/kg/day) and adrenalectomy before Ang II infusion. Rats received saline infusion were served as the Sham controls.ResultsRelative to the Sham animals, Ang II infusion significantly increased protein levels including Ang II AT1 receptors, StAR and AS as well as their tissue expression in the adrenal glands and heart, as identified by Western blot assay and immunohistochemical staining. Administration of telmisartan, significantly down‐regulated the protein level and expression of StAR and AS, but these changes were not altered by treatment with spironolactone, suggesting that Ang II AT1 receptors are involved as an upstream regulator and the blockade of aldosterone receptor does not affect the AT1/StAR/AS signaling. Following activation of these signaling cascades, Ang II infusion further augmented migration of macrophages, protein level of TGFβ1, phosphorylation of Smad2/3 and proliferation of myofibroblasts, in coincidence with enhanced perivascular/interstitial collagen deposition and cardiomyocyte hypertrophy, which all were significantly abrogated by either telmisartan or spironolactone treatment (all P<0.05 vs. Ang II group). However, removing adrenal glands by adrenalectomy did not fully suppress Ang II‐induced cell migration/proliferation and fibrosis/hypertrophy, indicating a role of aldosterone synthesized within the heart in the pathogenesis of Ang II induced cardiac injury.ConclusionsMyocardial fibrosis and hypertrophy stimulated by Ang II is associated with tissue‐specific activation of aldosterone synthesis, which are primarily mediated via AT1/StAR/AS signaling pathways. Understanding these maladaptive responses to Ang II could lead to the development of novel therapeutic strategy.Support or Funding InformationThis study was supported in part by grants from the Mercer University School of Medicine, the Medcen Community Health Foundation, Georgia and the National Natural Science Foundation of China (81470436).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Association between Daytime Sleepiness and Cardiometabolic Risk Factors
Authors: Danyluk Alexandria B. , Smith Kevin L. , Boeve Angelica R. , Bukartyk Jan , St Louis Erik K. , Somers Virend K. , Covassin Naima 
Published: June 2021

BackgroundSleep disturbances are increasingly common and associated with adverse health outcomes. Inadequate sleep may also produce daytime symptoms, such as excessive sleepiness. Growing research identifies daytime sleepiness as a risk factor for morbidity and mortality. However, it is unclear whether these associations are independent of the presence of sleep disordered breathing, a primary cause of hypersomnolence.ObjectiveIn this study, we sought to assess the relation between daytime sleepiness and established cardiometabolic risk factors, independently of obstructive sleep apnea.MethodsWe compiled data from 456 individuals (69% male, age 51.3±15.7 years) who participated in research studies performed in the Cardiovascular/Sleep Laboratory at Mayo Clinic and had complete sleepiness data. Height and weight were measured to calculate body mass index (BMI, kg/m2). Obesity was defined as BMI ≥30 kg/m2. Hypertension was determined as self‐reported diagnosis or taking antihypertensive medications. Diabetes mellitus was defined as patient‐reported diabetes or usage of insulin or antidiabetic drugs. Obstructive sleep apnea (OSA) was self‐reported or determined from polysomnography. Subjective daytime sleepiness was defined as an affirmative answer to the question “Are you usually sleepy during the daytime?”.ResultsDaytime sleepiness was reported by 51% of the subjects (n=231). Those with daytime sleepiness were more likely to be male (74.9% vs 62.3%, P=0.005), but the average age was similar between groups (51.6±17.3 years vs 51±14.1 years, P=0.67). BMI was greater among the subjects with perceived daytime sleepiness than in those without (32.2±7 kg/m2 vs 28.9±6.8 kg/m2, P<0.0001), and obesity was more frequent in the former group (62.9% vs 35.4%, P<0.0001). Prevalence of hypertension (37% vs 27.5%, P=0.03), diabetes (14% vs 6.7%, P=0.01), and OSA (18.2% vs 10.4%, P=0.035) was also higher in individuals reporting sleepiness during the day. In multivariable analysis adjusted for age, sex, and OSA, daytime sleepiness was associated with increased risk of obesity (OR=2.88, 95% CI 1.84–4.49, P<0.0001), hypertension (OR=1.73, 95% CI 1.04–2.87, P=0.034), and diabetes (OR=2.58, 95% CI 1.18–5.61, P=0.017).ConclusionDaytime sleepiness is associated with greater risk of obesity, hypertension and diabetes independently of comorbid OSA. Daytime sleepiness may be a novel target for preventative and therapeutic strategies aimed at improving cardiometabolic health.Support or Funding InformationNC is supported by American Heart Association grant 16SDG27250156, and Mayo Clinic Center for Clinical and Translational Science grant Marie Ingalls Cardiovascular Research Career Development Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute Aldosterone Administration Increases Vascular Resistance in Patients with Type 2 Diabetes
Authors: Finsen Stine Høyer , Mortensen Stefan P 
Published: June 2021

IntroductionIndividuals with type 2 diabetes (T2D) have an increased risk of developing macrovascular dysfunctions such as arteriosclerosis and reduced blood flow, which is not improved by blood‐glucose management. Chronic elevations in plasma aldosterone levels could contribute to endothelial dysfunction. A shift in the balance between constrictor and dilator responses to aldosterone could be involved in the detrimental actions of aldosterone.HypothesisWe tested the hypothesis that T2D is associated with a shift from a vasodilator to vasoconstrictor response to aldosterone.MethodsIn 6 subjects with T2D and 11 control subjects, we measured leg hemodynamics during 5 min of incremental doses of infused aldosterone (0.2 and 5 ng/min/L leg volume) in the femoral artery. Leg blood flow (LBF; ultrasound Doppler) and mean arterial blood pressure (MAP) was measured. Femoral arterial and venous blood samples were also collected. Data was analyzed with a one‐way repeated measures ANOVA (within groups) and two‐way ANOVA (between groups).ResultsIn the subjects with T2D, LBF and leg vascular conductance (LVC) decreased during aldosterone infusion at the high dose (P<0.05), whereas there was no change in LBF and LVC in the control group. Aldosterone infusion did not change MAP and there was no difference between groups. Venous aldosterone levels increased during infusion of aldosterone in both groups (P<0.05) and no differences were observed between groups.ConclusionThese preliminary results suggest that T2D is associated with a vasoconstrictor response to physiological levels of infused aldosterone.Support or Funding InformationIndependent Research Fund Denmark and The Region of Southern DenmarkThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of fructooligosaccharides on apoptosis and inflammation in enteroendocrine cells
Authors: Tuangkijkul Nuttha , Wongkrasant Preedajit , Muanprasat Chatchai 
Published: June 2021

Type 2 diabetes mellitus (T2DM) is considered as a chronic inflammatory disease. It has been found that TNF‐α‐induced inflammation of intestinal L‐cells leading to apoptosis that may cause a decrease in GLP‐1 secretion. Therefore, inhibition of inflammation‐mediated L cell apoptosis may provide the beneficial effect to T2DM patients. Most of prebiotics is known to suppress intestinal inflammation. This study aimed to investigate whether fructooligosaccharides (FOS), one of probiotics, on TNF‐α‐induced L cell inflammation and apoptosis. Indeed, the mouse secretin tumor cell line (STC‐1 cell) was used as an in vitro model of enteroendocrine L cells. We hypothesized that FOS might inhibit inflammatory signals via AMP‐activated protein kinase (AMPK), an intracellular energy sensor that known to suppress intestinal inflammation, which might result in inhibition of apoptosis. Immunofluorescence staining revealed that FOS did not suppress TNF‐α‐induced NF‐κB nuclear translocation in STC‐1 cell. Using cell death assay, Hoechst 33342 and ethidium homodimer‐1 co‐staining was performed. It was found that FOS significantly reduced number of apoptotic STC‐1 cells via AMPK‐independent mechanism. In conclusion, FOS may be useful for recovering the function of GLP‐1‐secreting cells that may be beneficial for T2DM patients.Support or Funding InformationThis work is supported by Tonkla Ramathibodi program, Faculty of Science Mahidol University and Thailand Research Fund and Mahidol University (BRG5980008)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in Body Composition and Insulin Action in Aging C57BL/6J Mice
Authors: Dalton Allison , Calzini Lucas , Tuluca Andrei , Hoyte Dakembay , Ives Stephen J , Reynolds Thomas H 
Published: June 2021

A paucity of data exists regarding sex‐differences in age‐related obesity and insulin resistance. The purpose of this study was to determine the effects of age and sex on insulin action and body composition in C57BL/6J mice. In aged (AG, 18 months old) male mice, glucose tolerance was diminished compared to young (YG, 6 months old) male mice (Area Under Curve: 95,103±6,818 vs 64,005±2,031, P=0.002). However, there was no age‐related decline in glucose or insulin tolerance in females. Body composition analysis revealed that AG males had significantly greater body mass (42.2±1.9 vs 30.0±0.4 g, P<0.0001), fat mass (18.7±2.0 vs 3.3±0.4 g, P<0.0001), body fat (43.0±3.0 vs 11.0±1.5%, P<0.0001) than YG males. In AG females, body mass (32.8±1.6 vs 26.3±0.9 g, P=0.02) was higher, but fat mass (13.3±2.0 vs 9.5±1.3 g, P=0.24) and body fat (37.8±4.8 vs 35.5±3.8%, P=0.67) were similar when compared to YG females. AG males had significantly higher body mass (42.2±1.9 vs 32.8±1.6 g, P=0.001) and fat mass (18.7±2.0 vs 13.3±2.0 g, P=0.04) compared to AG females; however, body fat (43.0±3.0 vs 37.8±4.8%, P=0.28) was similar. Although aging and obesity are associated with higher levels of oxidative stress, six weeks of treatment with MitoQ, a mitochondrial‐targeted antioxidant, did not reduce adiposity in AG male mice. Surprisingly, when AG male mice survive to 28 months of age, the obesity and insulin resistance that was observed at 18 months of age is reversed. In conclusion, our findings indicate that male mice, but not female mice, develop age‐related obesity and insulin resistance, a process that is reversed in the oldest of old mice.Support or Funding InformationNIA 1R15AG053790‐01This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in Microvascular Function and Circulating Biomarkers in Patients with Type 2 Diabetes Mellitus
Authors: Zanesco Angelina , Jarrete Aline Pincerato , Giollo‐Junior L , Martin Jose Fernando Vilela , Delbin Maria Andreia 
Published: June 2021

Cardiovascular diseases are the major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Evidence has shown that women have a greater risk for cardiovascular complications than men with T2DM, indicating a sex‐gender specific difference. Further studies regarding the mechanisms of sex differences are required for better prevention and treatment of diabetes complications in women. The aim of this study was to examine the microvascular endothelial function and circulating biomarkers in postmenopausal women (50–67 years) and age‐matched men with T2DM, without a history of cardiovascular events or complications. Participants without T2DM were also evaluated as control groups. This study was approved by the Ethical Committee of UNESP and UNICAMP (Number: 1.548.242). The eligible participants composed 4 groups: postmenopausal women (W) (n=16); postmenopausal women with T2DM (DW) (n=15); middle‐aged men (M) (n=15); middle‐aged men with T2DM (DM) (n=14). All participants were physically inactive, non‐smokers and not taking hormonal replacement or on insulin therapy. Both diabetic groups were on oral hypoglycemic therapy. After resting blood pressure measurement, the microvascular endothelial function was performed using EndoPAT 2000 and expressed as the reactive hyperemic index (RHI). Fasting blood samples were collected for biochemical analyses. All groups were age‐matched and the time of T2DM diagnosis was similar between the groups (DW: 7.5±1.3 DM: 9.6±2.3 yrs). Anthropometric parameters, systolic and diastolic blood pressure, lipid profile, HbA1c and insulin levels were not different between women and men with diabetes. On the other hand, DM showed a higher blood glucose level and HOMA‐IR compared with DW. Regarding microvascular endothelial function, RHI was similar between DW (1.97±0.14) and DM (1.93±0.12) without alterations in circulating biomarkers: adiponectin, N‐ɛ‐(carboxymethyl) lysine (CML), nitrite/nitrate (NOx−), transforming growth factor‐β (TGF‐β), tumor necrosis factor‐α (TNF‐α) and C‐reactive protein (CRP). Nevertheless, when diabetic groups were compared with the control groups, we observed a higher body mass index (BMI) and abdominal circumference in DW compared with its respective control group. Besides that, DW also presented impaired RHI and a lower adiponectin level associated with increased CML and NOx− concentrations compared with W group (RHI: 2.51±0.13). All these alterations were not found in DM compared with its respective control group. Our findings show that circulatory biomarkers disturbance and microvascular dysfunction are present in diabetic women showing that this population is more affected by the deleterious effects of T2DM than men.Support or Funding InformationCNPq and FAPESPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modulation of Nω‐nitro‐L‐arginine methyl ester (L‐NAME)‐Induced Hypertension and Cardio‐renal Oxidative Stress by Methanol Extract of Persea americana Root
Authors: Adejumobi Olumuyiwa Abiola , Oyagbemi Ademola Adetokunbo , Akoleowo Olabimpe Olufunmilayo , Omotosho Oladipo O. , Yakubu Momoh , Omobowale Temidayo Olutayo , Adedapo Adeolu A. 
Published: June 2021

Hypertension is the leading cause of cardiovascular morbidity and mortality. Uncontrolled hypertension causes end organ damage resulting in hypertensive cardiomyopathy and nephropathy. P. americana root extract (PARE) is commonly used the management of hypertension in Nigeria traditional medicine.In this study, we investigated modulatory effects of PARE on L‐NAME induced hypertension, oxidative stress and cardio‐renal complicationsSixty male rats (wistar strain) were used in this study, and they were randomly divided into six experimental groups with ten rats in each group. Group A served as the controls and they received distilled water only for the period of 21 days. Group B was given L‐NAME only at 40mg/kg while groups C, D and E were given a daily dose of L‐NAME at 40 mg/kg and methanol root extract at respective dose of 100mg/kg, 200mg/kg and 400mg/kg for 21 days. Group F was given a daily dose of L‐name+ Lisinopril (0.25mg/kg) orally for 21 days. L‐name was given at 40mg/kg daily. Blood pressure measurements were recorded in conscious animals by tail cuff plethysmography . Biochemical assays were carried out on the serum, cardiac and renal tissues to assess the enzymatic and non‐enzymatic antioxidant defense system. Immunohistochemistry was also done on cardiac and renal tissues.Treatment with L‐NAME caused a significant (p <0.05) increase in systolic, diastolic and mean arterial blood pressure and markers of oxidative stress in cardiac and renal tissues. Immunohistochemistry showed increased expressions of CTn1, NRF2 and NFkB in the heart tissues and KIM‐1, NRF2 and NFkB in the kidney tissues of the group treated with L‐NAME alone compared to the control. Treatment with PARE caused a significant (P<0.05) decrease in blood pressure, an improvement in antioxidant defense systems, reduction in markers of oxidative stress, cardiac and renal injury and inflammation comparable with that of lisinopril..The results obtained from this study suggest that PARE can modulate high blood pressure with associated end organ damage and cardio‐renal oxidative stress in L‐NAME induced hypertensionThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of BKCa channels in smooth muscle cells of mesenteric artery from type 1 diabetic rats
Authors: Hernández‐Garcia Ana P , Hernández‐Méndez Aurelio , Chi‐Ahumada Erika , Algara‐Suárez Paola , Espinosa‐Tanguma Ricardo 
Published: June 2021

High conductance calcium‐activated potassium channels (BKCa) play a very important role in the regulation of arterial vascular tone through the hyperpolarization of the cell membrane. Diverse studies in blood vessels from different vascular beds in animal models with type I and II diabetes mellitus (DM) as well as in patients with type II diabetes have shown a decrease in the BK channels functional response which is probably related with cardiovascular complications secondary to this pathology that is the main cause of mortality in these patients.ObjectiveTo explore the expression and role of the BKCa channels in the contractility of the Mesenteric artery of Type I diabetic rats induced with streptozotocin.MethodsWe conducted isometric tension experiments in mesenteric artery rings (>500) to evaluate the function of the BKCa channel when pharmacologically activated with NS1619, a specific activator drug for this channel, or inhibiting it with Iberotoxin (Ibtx) a toxin that specifically blocks these channels. And with the purpose of knowing if BKCa channels are expressed in these arterial beds we conducted inmunofluorescence studies.ResultsWe observerd a small but not significant response to both activator and inhibitor of the BKCa channels in both control and experimental groups. The inmunofluorescence images indicated that the alfa subunit (the pore subunit) and beta 1 (modulator of the BKCa channel activity) are mostly expressed intracelullarly in endothelial cells and in the smooth muscle of these vessels. This suggests that the lack of response to NS1619 and IBtx is due to the fact that the channel is intracelullar and therefore its participation in the determination of muscle tone of the mesenteric artery is not significant. In contrast, preliminary results of isometric tension in first‐order rat mesenteric artery rings (approximately 400 μm in diameter), show a great participation of the BKCa channels in the regulation of the arterial tone of these vessels, by diminishing in about 80% the tension originated when contracting said rings with phenylephrine.ConclusionsBased on these results, we can conclude at present that the BKCa channels have a greater participation in the maintenance of muscle tone of small arteries (resistance) but not in big arteries (conductive) and that the type I diabetes does not affect the BKCa function in large conduncance arteries.Support or Funding InformationSupported by Conacyt 223350 to RETThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.