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Pubblicazioni recenti - cardiovascular
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Obstructive sleep apnoea in adult patients post-tonsillectomy.
Sleep Med2020 Nov;78():189-192. doi: S1389-9457(20)30516-5.
Riha Renata L, Kotoulas Serafeim-Chrysovalantis, Pataka Athanasia, Kvamme John Arthur, Joppa Pavol, Hedner Jan, ,
Abstract
BACKGROUND:
The impact of removing the upper airway lymphoid tissue and in particular, tonsillectomy, in adults with OSA has not been demonstrated in large populations.
AIMS:
To compare the severity of OSA and the prevalence of cardiovascular, metabolic and respiratory co-morbidities between patients with OSA who had undergone previous tonsillectomy and those who had not.
METHODS:
The 19,711 participants in this study came from the European sleep apnea database (ESADA) which comprises data from unselected adult patients aged 18-80 years with a history of symptoms suggestive of OSA referred to sleep centers throughout Europe.
RESULTS:
There were no differences between the two groups in terms of sex ratio and age (146 patients with previous tonsillectomy vs. 19565 patients without). Patients who had undergone tonsillectomy had a lower body mass index (29.3 ± 5.2 kg/m vs 32.2 ± 6.6 kg/m, p < 0.001), lower subjective sleep latency (17.1 ± 17.8 min vs 25.5 ± 30.4 min, p = 0.001), lower ODI (15.7 ± 18.3 events/hour vs 30.7 ± 26.1 events/hour, p < 0.001), and SpO<90% time during sleep (21.8 ± 47.5 min vs 52.6 ± 80.8 min, p < 0.001). OSA patients with tonsillectomy had a lower prevalence of Type II diabetes mellitus (p = 0.001), hypertension (p < 0.001) and a higher prevalence of hyperlipidemia (p < 0.001) and were less likely to be commenced on CPAP (p < 0.001).
CONCLUSION:
In a large population of almost 20,000 OSA patients from across Europe, patients who had undergone tonsillectomy presented with less severe OSA at time of diagnosis, and had a lower prevalence of Type II diabetes mellitus and cardiovascular co-morbidities.
Copyright © 2020. Published by Elsevier B.V.
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A heterozygous MYH7 (c. 2156G > A) mutant human induced pluripotent stem cell line (ZZUNEUi020-A) generated from a patient with hypertrophic cardiomyopathy.
Stem Cell Res2021 Jan;51():102158. doi: S1873-5061(21)00004-0.
Li Xiaowei, Fu Wanrong, Guo Guangli, Liu Mengduan, Du Wenting, Zhao Jing, Liu Yangyang, Wang Lu, Dong Jianzeng, Zhao Xiaoyan,
Abstract
Hypertrophic cardiomyopathy (HCM) is a heterogeneous myocardial disease often caused by sarcomeric gene mutations. MYH7 is one of the most common genes associated with HCM. In this study, we generated a human induced pluripotent stem cell (iPSC) line ZZUNEUi020-A from peripheral blood mononuclear cells of a female HCM patient with the p. R719Q (c. 2156G > A) mutation in MYH7. This cell line expressed pluripotency markers, showed normal female karyotype and could differentiate into all three germ layers in vitro.
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
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Assessment of cardiac implantable electric device lead perforation using a metal artifact reduction algorithm in cardiac computed tomography.
Eur J Radiol2021 Jan;136():109530. doi: S0720-048X(21)00010-3.
Kidoh Masafumi, Oda Seitaro, Nakato Kengo, Sakabe Daisuke, Kanazawa Hisanori, Takashio Seiji, Nakaura Takeshi, Nagayama Yasunori, Sasao Akira, Hatemura Masahiro, Funama Yoshinori, Kaikita Koichi, Tsujita Kenichi, Ikeda Osamu, Azuma Minako, Hirai Toshinori,
Abstract
PURPOSE:
CT is considered the non-invasive gold standard for evaluating cardiac implantable electronic devices (CIEDs) lead perforation, but metal artifacts caused by the lead tip affect the image quality and make a definitive diagnosis challenging. We compared the performances of the metal artifact reduction (MAR) algorithm and the conventional algorithm for identification of the right ventricular (RV) lead tip position in cardiac CT studies of patients with CIEDs.
METHOD:
Forty-seven consecutive patients (26 men; age 70.3?±?15.4 years) with CIEDs underwent cardiac CT. Using the conventional and MAR algorithm, two image reconstructions were performed for each scan. We calculated the artifact index (AI) to assess the quantitative capability of the MAR algorithm for artifact reduction and visually assessed the RV lead tip position on both images as follows: non-perforation, perforation, and equivocal.
RESULTS:
The mean AIs were significantly lower with the MAR algorithm than with the conventional algorithm (96.7?±?40.1 HU vs. 284.6?±?134.1 HU, P?
CONCLUSIONS:
The MAR algorithm effectively reduced metal artifacts and allowed us to diagnose the presence or absence of perforation in all cases, whereas definitive diagnosis was difficult with the use of conventional algorithm in 27.7 % of cases.
Copyright © 2021 Elsevier B.V. All rights reserved.
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Challenges of Combining Opioids and P2Y Inhibitors in Acute Coronary Syndrome: Should the Future Be Opioid Free?
Curr Probl Cardiol2020 Dec;46(4):100781. doi: S0146-2806(20)30257-7.
Moore Catherine H, Lukas Jack G, Cave Brandon E, Khouzam Rami N,
Abstract
Morphine has been long recognized as standard of care in the treatment of acute coronary syndrome (ACS) patients; however, its safety has recently been called into question due to a drug interaction with P2Y inhibitors. Opioids, given in combination with P2Y inhibitors, can reduce antiplatelet effects by slowing gastrointestinal motility and ultimately reducing drug absorption. While there are proposed benefits of opioids in ACS patients, conflicting data regarding clinical outcomes exist. The majority of clinical data slightly favors opioid use in ST-elevation myocardial infarction over non-ST-elevation myocardial infarction, although trends for increased myocardial infarction are present in both settings. Current practice should be aimed at discerning the need for routine opioid use in ACS. Alternative strategies may be needed to overcome these interactions; however, no robust data are currently available to support these treatment options. Future research should be aimed at non-opioid treatment options in ACS, as opioid use remains controversial in this population.
Copyright © 2020 Elsevier Inc. All rights reserved.
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Predictive value of lower extremity color doppler ultrasonography before knee arthroplasty on a postoperative cardiovascular event.
Knee2021 Jan;28():266-272. doi: S0968-0160(20)30410-5.
Alt?nayak Harun, Balta Orhan,
Abstract
BACKGROUND:
The study intended to determine the presence of lower limb arterial calcification (LLAC) in lower extremity color Doppler ultrasonography (CDUS) before primary total knee arthroplasty (TKA) and its relation with cardiovascular events (CVE) during knee arthroplasty and the postoperative period, as well as to investigate its effect on surgical risk estimation.
METHODS:
We designed this study as a retrospective cohort study. The study comprised 467 patients who met the inclusion criteria and had surgery for a primary gonarthrosis diagnosis between January 2005 and December 2015 were included. In the study group, patients with arterial calcification in the lower extremity CDUS were included; however, those reported not to have it were included in the control group. The research data were obtained from preoperative anesthesia records and patient medical records.
RESULTS:
72% of the sample had preoperative cardiovascular comorbidity. There was no difference between the groups in terms of comorbidities, except for congestive heart failure (CHF) and peripheral artery disease (PAD). The groups did not differ in terms of ASA scores, either. Both pre- and post-operative CVEs, i.e., ischemic heart disease, dysrhythmia, and CHF, were statistically high in the study group. In terms of postoperative mortality, there was no statistical difference between the groups.
CONCLUSION:
The study demonstrates that the presence of LLAC in CDUS is associated with increased risk of perioperative cardiovascular events (CVEs). Ultrasonographic detection of LLAC may give some idea the surgeon about the requirement for additional preoperative cardiac examinations.
Copyright © 2020 Elsevier B.V. All rights reserved.
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Better Appreciation of the Mechanical Maladaptive Remodeling in Aortic Stenosis: Imaging in Proper Perspective.
J Am Soc Echocardiogr2021 Jan;():. doi: S0894-7317(21)00015-8.
Lopez-Candales Angel, Vallurupalli Srikanth,
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Systematic fluoroscopic-echocardiographic fusion imaging protocol for transcatheter edge-to-edge mitral valve repair intraprocedural monitoring.
J Am Soc Echocardiogr2021 Jan;():. doi: S0894-7317(21)00014-6.
Melillo Francesco, Fisicaro Andrea, Stella Stefano, Ancona Francesco, Capogrosso Cristina, Ingallina Giacomo, Maccagni Davive, Romano Vittorio, Ruggeri Stefania, Godino Cosmo, Latib Azeem, Montorfano Matteo, Colombo Antonio, Agricola Eustachio,
Abstract
BACKGROUND:
Whether fluoroscopic-echocardiographic fusion imaging (FI) might represent an added value for intraprocedural guidance during transcatheter edge-to-edge mitral valve repair (TMVr) is yet unknown and few data exist regarding safety and feasibility of the novel technology.
METHODS:
The aim of this single-centre study was to test and validate a FI protocol for intraprocedural monitoring of TMVr and assess its clinical usefulness. Eighty patients underwent MitraClip procedure using FI guidance (FI+) for either degenerative (DMR) (35%) or functional (FMR) (65%) mitral regurgitation and were compared to the last 80 patients before FI introduction treated with conventional echo and fluoroscopic monitoring (FI-).
RESULTS:
The number of patients treated for FMR and DMR was similar between FI+ and FI- group, as well as the number of devices implanted (1.51±0.5 vs. 1.58±0.6; p=0.46). Prevalence of complex mitral anatomy for percutaneous repair was high (32.5%, up to 39.2% in the hybrid arm). Fluoroscopy time was significantly lower in FI+ patients (37.3±14.6 vs. 48.3±28.3 min; p=0.003), but not kerma area product (91.5±74.1 vs. 108.8±105.0 Gy cm; p=0.23) or procedural time (92.2±36.1 vs. 103.1±42.7 min; p=0.086). After adjusting for confounding factors (XT device and complex anatomy), fusion imaging reduced fluoroscopy time (coeff -10.4 min; 95% CI -18.03 - -2.82; p=0.007) and improved procedural success at the end of the procedure (OR 2.87 95% CI 1.00 - 8.24, p=0.049) and discharge (OR 2.24, 95% CI 1.04 - 4.80; p=0.039). Peri-procedural complications rate was similar in both groups (8.9% vs. 13.0%; p=0.40).
CONCLUSIONS:
Our study described the systematic use of a FI protocol for intraprocedural guidance during TMVr demonstrating a reduction of the fluoroscopy time and improvement in procedural success in a population with high prevalence of challenging mitral anatomy for percutaneous repair.
Copyright © 2021. Published by Elsevier Inc.
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Cardiovascular dysfunction in children exposed to preeclampsia during fetal life.
J Am Soc Echocardiogr2021 Jan;():. doi: S0894-7317(21)00012-2.
Hoodbhoy Zahra, Mohammed Nuruddin, Rozi Shafquat, Aslam Nadeem, Mohsin Shazia, Ashiqali Salima, Ali Hina, Sattar Saima, Chowdhury Devyani, Hasan Babar Sultan,
Abstract
OBJECTIVE:
Keeping in view the Developmental Origin of Health and Disease hypothesis, this study aimed to assess differences in cardiac and vascular structure and function in children exposed to preeclampsia in-utero as compared to those of normotensive mothers. We hypothesized that children exposed to preeclampsia had altered cardiac and vascular structure and function as compared to the unexposed group.
METHODS:
This was a retrospective cohort study which included children between 2-10 years of age born to mothers with and without exposure to preeclampsia in-utero (n= 80 in each group). Myocardial morphology and function using echocardiogram and carotid intima-media thickness and pulse wave velocity were performed. Multivariable linear regression was used to compare preeclampsia exposed and non-exposed groups. Subgroup analysis to assess differences between early vs late onset preeclampsia was also performed.
RESULTS:
Forty one percent (n=33) mothers had early onset preeclampsia. Children in the exposed group had significantly higher prevalence of Stage 1 systolic and diastolic hypertension (22%, n=18 and 35%, n=18 respectively) as compared to the unexposed group (9%, n=7 and 19% n =15 respectively, p=0.01). Children in the exposed group also had higher pulse wave velocity as compared to unexposed group (0.42 +/- 0.1 vs 0.39 +/- 0.1, p=0.03). Subgroup analysis revealed that blood pressure and pulse wave velocity changes were primarily determined by early onset preeclampsia. There was no significant difference in cardiac morphology or systolic and diastolic function between the exposed and unexposed groups.
CONCLUSION:
In-utero exposure to preeclampsia has an effect on the vascular function in children aged 2-10 years, primarily related to early onset disease. Routine blood pressure screening should be recommended for such children.
Copyright © 2021. Published by Elsevier Inc.
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A Novel Approach to Medical Management of Heart Failure with Reduced Ejection Fraction.
Can J Cardiol2021 Jan;():. doi: S0828-282X(21)00046-5.
Miller Robert Jh, Howlett Jonathan G, Fine Nowell M,
Abstract
The advent of newly available medical therapies for HFrEF has resulted in many potential therapeutic combinations, increasing treatment complexity. Publication of expert consensus guidelines and initiative aimed to improve treatment implementation have emphasized sequential, stepwise initiation and titration of medical therapy, which is labour intensive. Data taken from heart failure registries shows suboptimal use of medications, prolonged titration time and consequently little change in dose intensity, all of which, indicate therapeutic inertia. Recently published evidence indicates that four medication classes (1. renin-angiotensin-neprilysin inhibitors, 2. beta-blockers, 3. mineralocorticoid antagonists and 4. sodium-glucose cotransporter inhibitors), which we refer to as Foundational Therapy, confer rapid and robust reduction in both morbidity and mortality in most patients with HFrEF, and that they work in additive fashion. Additional morbidity and/or mortality may be observed following addition of several Personalized Therapies in specific subgroups of patients. In this review, we discuss mechanisms of action of these therapies and propose a framework for their implementation based on several principles. These include the critical importance of rapid initiation of all 4 Foundational Therapies followed by their titration to target doses, emphasis on multiple simultaneous drug changes with each patient encounter, attention to patient-specific factors in choice of medication class, leveraging inpatient care, use of the entire health care team and alternative (i.e. virtual visits) modes of care. We have incorporated these principles into a 'Cluster Scheme' designed to facilitate timely and optimal medical treatment for patients with HFrEF.
Copyright © 2021. Published by Elsevier Inc.
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Research progress on the interaction between circadian clock and early vascular aging.
Exp Gerontol2021 Jan;():111241. doi: S0531-5565(21)00016-4.
Chen Zhuoying, Xiong Zhi-Fan, Liu Xiangjie,
Abstract
Considerable researches implicate that the circadian clock regulates the responsive rhythms of organs and sets the orderly aging process of cells indirectly. It influences an array of diverse biological process including intestinal flora, peripheral inflammatory responses, and redox homeostasis. People with sleep disoders and other kinds of circadian disruptions are prone to have vascular aging earlier. Meanwhile, those people are always faced with chronic vascular inflammation. It has not been elucidated that the specific mechanism of the interaction between the circadian system and early vascular aging. To explore the biphasic relationship between vascular aging and the circadian system, we summarize what is linking circadian clock with early vascular aging through four major prospect: inflammatory process, oxidative stress response, intestinal flora, and cellular senescence. Meanwhile, we discuss the hypothesis that the deterioration of circadian rhythms may exacerbate the process of early vascular aging, leading to the cardiovascular diseases. It will help us to provide new ideas for understanding the process of vascular aging and exploring the possible ways to design personalized chronotherapies.
Copyright © 2018. Published by Elsevier Inc.
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Adding high-sensitivity C-reactive protein to frailty assessment to predict mortality and cardiovascular events in elderly inpatients with cardiovascular disease.
Exp Gerontol2021 Jan;():111235. doi: S0531-5565(21)00010-3.
Yao Si-Min, Zheng Pei-Pei, Wan Yu-Hao, Dong Wei, Miao Guo-Bin, Wang Hua, Yang Jie-Fu,
Abstract
OBJECTIVE:
Chronic inflammation is associated with major adverse cardiovascular events (MACEs), mortality, and frailty. Our aim was to add high-sensitivity C-reactive protein (hsCRP) to the frailty assessment to predict its association with prognosis of older adults with cardiovascular disease (CVD).
METHODS:
A comprehensive geriatric assessment was conducted at baseline in 720 in-patients aged ?65?years with CVD. We divided the population into frailty and non-frailty groups according to the Fried phenotype, and hsCRP was further combined with frailty to stratify all patients into c-frailty and non-c-frailty groups. Predictive validity was tested using Cox proportional hazards regression model analysis and the discriminative ability was evaluated by receiver operating characteristic (ROC) curves.
RESULTS:
Of all the subjects enrolled, 51.0% were male and the mean age was 75.32?±?6.52?years. The all-cause death and MACE rate was 6.4% at the 1-year follow-up. Frailty and c-frailty were independent predictors of all-cause death and MACE (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.35-4.83, p?=?0.004; HR: 3.67, 95% CI: 1.83-7.39, p?
CONCLUSION:
Adding hsCRP to the frailty assessment is helpful to identify a subgroup of older CVD patients with a higher risk of death and MACE over a period of 1?year.
TRIAL REGISTRATION:
ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.
Copyright © 2018. Published by Elsevier Inc.
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Prediction of 10-year Mortality using hs-CRP in Chinese People with Hyperglycemia: Findings from the Da Qing Diabetes Prevention Outcomes Study.
Diabetes Res Clin Pract2021 Jan;():108668. doi: S0168-8227(21)00021-8.
Qian Xin, He Siyao, Wang Jinping, Gong Qiuhong, An Yali, Li Hui, Chen Yanyan, Li Guangwei,
Abstract
AIMS:
To examine whether high-sensitivity C-reactive protein (hs-CRP) can predict all-cause death in Chinese adults with hyperglycemia.
METHODS:
All the 237 diabetes and 49 prediabetes recruited in the study were evolved from the participants with impaired glucose tolerance in the original Da Qing Diabetes Study. Blood hs-CRP level was measured at 2006. Ten-year outcome of death was traced from 2006 to 2016. Cox model was used to analyse the association between hs-CRP level and the risk of all-cause death occurred over the subsequent 10 years.
RESULTS:
During the follow-up, death occurred in 36 (37.9%) subjects in the highest hs-CRP tertile group (hs-CRP >2.16 mg/L) and 19 (20.0%) in the lowest hs-CRP tertile group (hs-CRP <0.82 mg/L, p < 0.05). The corresponding incidence of all-cause death (per 1,000 person-years) was 44.7 (95% CI 30.1-59.3) and 21.6 (95% CI 11.9-31.3) in the two groups respectively (p <0.0001). The highest hs-CRP tertile was associated with the increased risk of all-cause death significantly (hazard ratio 1.88, 95% CI 1.07-3.32) after controlling for traditional risk factors.
CONCLUSIONS:
Serum hs-CRP was predictive of 10-year all-cause death in Chinese adults with hyperglycemia, suggesting the impact of low-grade inflammation on mortality deserves more attention.
Copyright © 2021. Published by Elsevier B.V.
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Microbiota thrombus colonization may influence AtheRo-thrombosIs in hyperglycemic pAtieNts with ST sEgment eLevation myocardiaLinfArction (STEMI). MARIANELLA study.
Diabetes Res Clin Pract2021 Jan;():108670. doi: S0168-8227(21)00023-1.
Sardu Celestino, Consiglia Trotta Maria, Santella Biagio, D'Onofrio Nunzia, Barbieri Michelangela, Rosaria Rizzo Maria, Carlo Sasso Ferdinando, Scisciola Lucia, Turriziani Fabrizio, Torella Michele, Portoghese Michele, Loreni Francesco, Mureddu Simone, Antonietta Lepore Maria, Galdiero Massimiliano, Franci Gianluigi, Folliero Veronica, Petrillo Arianna, Boatti Lara, Minicucci Fabio, Mauro Ciro, Calabrò Paolo, De Feo Marisa, Luisa Balestrieri Maria, Ercolini Danilo, D'Amico Michele, Paolisso Giuseppe, Galdiero Marilena, Marfella Raffaele,
Abstract
OBJECTIVES:
We examined the association of the coronary thrombus microbiota and relative metabolites with major adverse cardiovascular events (MACE) in hyperglycemic patients with ST segment elevation myocardial infarction (STEMI).
BACKGROUND:
Hyperglycemia during STEMI may affect both development and progression of coronary thrombus via gut and thrombus microbiota modifications.
METHODS:
We undertook an observational cohort study of 146 first STEMI patients treated with primary percutaneous coronary intervention (PPCI) and thrombus-aspiration (TA). Patients were clustered, based on admission blood glucose levels, in hyperglycemic (?140 mg/dl) and normoglycemic (<140 mg/dl). We analyzed gut and thrombus microbiota in all patients. Moreover, we assessed TMAO, CD40L and von Willebrand Factor (vWF) in coronary thrombi. Cox regressions were used for the association between Prevotellaspp. and TMAO terziles and MACE. MACE endpoint at 1 year included death, re-infarction, unstable angina.
RESULTS:
In fecal and thrombus samples, we observed a significantly different prevalence of both Prevotellaspp.and Alistipesspp. between patients with hyperglycemia (n=56) and those with normal glucose levels (n=90). The abundance of Prevotella increased in hyperglycemic vs normoglycemic patients whereas the contrary was observed for Alistipes. Interestingly, in coronary thrombus, the content of Prevotella was associated with admission blood glucose levels (p<0.01), thrombus dimensions (p<0.01), TMAO, CDL40 (p<0.01) and vWF (p<0.01) coronary thrombus contents. Multivariate Cox-analysis disclosed a reduced survival in patients with high levels of Prevotella and TMAO in coronary thrombus as compared to patients with low levels of Prevotella and TMAO, after 1-year follow up.
CONCLUSIONS:
Hyperglycemia during STEMI may increase coronary thrombus burden via gut and thrombus microbiota dysbiosis characterized by an increase of Prevotella and TMAO content in thrombi.
CLINICAL TRIAL REGISTRATION:
NCT03439592. September 30, 2016 Ethic Committee Vanvitelli University: 268/2016.
Copyright © 2021 Elsevier B.V. All rights reserved.
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The physiological benefits of sitting less and moving more: Opportunities for future research.
Prog Cardiovasc Dis2021 Jan;():. doi: S0033-0620(21)00003-7.
Hwang Chueh-Lung, Chen Szu-Hua, Chou Chih-Hsuan, Grigoriadis Georgios, Liao Tzu-Chieh, Fancher Ibra S, Arena Ross, Phillips Shane A,
Abstract
Sedentary behavior (SB) and physical activity (PA) are important risk factors of cardiovascular disease morbidity and mortality. In addition to increasing the amount of moderate-to-vigorous PA; MVPA, the current PA guidelines recommend that adults should reduce SB, or any waking activity performed while sitting, reclining, or lying, with low energy expenditure. While mounting evidence has emphasized the benefits of increasing MVPA, little is focused on the effect of SB on health. Therefore, this review discusses the pathophysiological effects of SB and the potential physiological benefits of reducing/breaking up SB at the levels below the current guidelines for PA. Such knowledge is important, given the majority of the United States population performs insufficient or no MVPA and are at high risk of being negatively impacted by SB. Interventions targeting sedentary time, such as breaking up SB by standing and moving, may be safe, feasible, and applicable to execute daily for a wider range of the population. This review also discusses the importance of monitoring SB in the era of the coronavirus disease 2019 (COVID-19) pandemic and the clinical implications of sitting less and moving more.
Copyright © 2018. Published by Elsevier Inc.
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Androglobin gene expression patterns and FOXJ1-dependent regulation indicate its functional association with ciliogenesis.
J Biol Chem2021 Jan;():100291. doi: S0021-9258(21)00059-4.
Koay Teng Wei, Osterhof Carina, Orlando Ilaria M C, Keppner Anna, Andre Daniel, Yousefian Schayan, Alonso María Suárez, Correia Miguel, Markworth Robert, Schödel Johannes, Hankeln Thomas, Hoogewijs David,
Abstract
Androglobin (ADGB) represents the latest addition to the globin superfamily in metazoans. The chimeric protein comprises a calpain domain and a unique circularly permutated globin domain. ADGB expression levels are most abundant in mammalian testis, but its cell type-specific expression, regulation and function have remained unexplored. Analyzing bulk and single-cell mRNA-Seq data from mammalian tissues, we found that -in addition to testes- ADGB is prominently expressed in the female reproductive tract, lungs and brain, specifically being associated with cell types forming motile cilia. Correlation analysis suggested co-regulation of ADGB with FOXJ1, a crucial transcription factor of ciliogenesis. Investigating the transcriptional regulation of the ADGB gene, we characterized its promoter using epigenomic datasets, exogenous promoter-dependent luciferase assays and CRISPR/dCas9-VPR-mediated activation approaches. Reporter gene assays revealed that FOXJ1 indeed substantially enhanced luciferase activity driven by the ADGB promoter. ChIP assays confirmed binding of FOXJ1 to the endogenous ADGB promoter region. We dissected the minimal sequence required for FOXJ1-dependent regulation and fine mapped the FOXJ1 binding site to two evolutionarily conserved regions within the ADGB promoter. FOXJ1 overexpression significantly increased endogenous ADGB mRNA levels in HEK293 and MCF-7 cells. Similar results were observed upon RFX2 overexpression, another key transcription factor in ciliogenesis. The complex transcriptional regulation of the ADGB locus was illustrated by identifying a distal enhancer, responsible for synergistic regulation by RFX2 and FOXJ1. Finally, cell culture studies indicated an ADGB-dependent increase in the number of ciliated cells upon overexpression of the full-length protein, confirming a ciliogenesis-associated role of ADGB in mammals.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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Pterostilbene influences glycemia and lipidemia and enhances antioxidant status in the liver of rats that consumed sucrose solution.
Life Sci2021 Jan;():119048. doi: S0024-3205(21)00033-3.
de Morais Juliana Maria Bitencourt, Cruz Ellen Mayara Souza, da Rosa Carlos Vinícius Dalto, Cesário Roberta Carvalho, Comar Jurandir Fernando, Moreira Carolina Campos Lima, de Almeida Chuffa Luiz Gustavo, Seiva Fábio Rodrigues Ferreira,
Abstract
AIMS:
The present study investigated the potential effects of pterostilbene (PT) on glycemic and lipid profiles, fat storage, cardiovascular indices, and hepatic parameters of rats fed with sucrose solution.
MAIN METHODS:
24 male Wistar rats received either drinking water or a 40% sucrose solution over a period of 140?days. After this period, animals were randomly allocated into four groups (n?=?6): Control (C), C?+?Pterostilbene (PT), Sucrose (S), and S?+?PT. Pterostilbene (40?mg/kg) was given orally for 45 consecutive days.
KEY FINDINGS:
Pterostilbene did not influence morphometric and nutritional parameters. The insulin sensitivity index TyG was elevated in the C?+?PT group (p?
SIGNIFICANCE:
PT effects depends on the type of diet the animals were submitted. In rats fed with sucrose-solution, PT confirmed its positive effects, improving glucose and lipid profile, and acting as a potent antioxidant. The effects of PT on rats that consumed a normal diet were very discrete or even undesirable. We suggest caution with indiscriminate consume of natural compounds by healthy subjects.
Copyright © 2018. Published by Elsevier Inc.
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Testosterone stimulates cholesterol clearance from human macrophages by activating LXR?.
Life Sci2021 Jan;():119040. doi: S0024-3205(21)00025-4.
Kilby Elizabeth L, Kelly Daniel M, Jones T Hugh,
Abstract
AIMS:
Low testosterone in men is associated with increased cardiovascular events and mortality. Testosterone has beneficial effects on several cardiovascular risk factors including cholesterol, endothelial dysfunction and inflammation as key mediators of atherosclerosis. Although evidence suggests testosterone is anti-atherogenic, its mechanism of action is unknown. The present study investigates whether testosterone exerts anti-atherogenic effects by stimulating cholesterol clearance from macrophages via activation of liver X receptor (LXR?), a nuclear master regulator of cellular cholesterol homeostasis, lipid regulation, and inflammation.
MAIN METHODS:
Using human monocyte THP-1 cells differentiated into macrophages, the effect of testosterone (1-10?nM) treatment (24-72?h) on the expression of LXR? and LXR- targets apolipoprotein E (APOE), ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding transcription factor 1 (SREBF1) and fatty acid synthase (FAS), was investigated via qPCR and western blotting, with or without androgen receptor blockade with flutamide or LXR antagonism with CPPSS-50. Cholesterol clearance was measured by monitoring fluorescent dehydroergosterol (DHE) cellular clearance and ABCA1 cellular translocation was observed via immunocytochemistry in testosterone treated macrophages.
KEY FINDINGS:
Testosterone increased mRNA and protein expression of LXR?, APOE, ABCA1, SREBF1 and FAS. These effects were blocked by flutamide and independently by LXR antagonism with CPPSS-50. Furthermore testosterone stimulated cholesterol clearance from the macrophages and promoted the translocation of ABCA1 toward the cell membrane.
SIGNIFICANCE:
Testosterone acts via androgen receptor-dependent pathways to stimulate LXR? and downstream targets to induce cholesterol clearance in human macrophages. This may, in part, explain the anti-atherogenic effects of testosterone frequently seen clinically.
Copyright © 2018. Published by Elsevier Inc.
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Cultured Cardiac Fibroblasts and Myofibroblasts Express Sushi Containing Domain 2 and Assemble a Unique Fibronectin Rich Matrix.
Exp Cell Res2021 Jan;():112489. doi: S0014-4827(21)00020-3.
Schmuck Eric G, Roy Sushmita, Dhillon Anisa, Walker Sydney, Spinali Keith, Colevas Sophia, Zhou Tianhua, Chhabra Gagan, Liu Yuming, Kader Sagar Md Abdul, Childs Charlie J, Kink John A, Eliceiri Kevin W, Hematti Peiman, Raval Amish N,
Abstract
Cardiac fibroblasts and myofibroblasts assemble and maintain extracellular matrix during normal development and following injury. Culture expansion of these cells yield a bioengineered matrix that could lead to intriguing therapeutic opportunities. For example, we reported that cultured rat cardiac fibroblasts form a matrix that can be used to delivery therapeutic stem cells. Furthermore, we reported that matrix derived from cultured human cardiac fibroblasts/myofibroblasts converted monocytes into macrophages that express interesting anti-inflammatory and pro-angiogenic properties. Expanding these matrix investigations require characterization of the source cells for quality control. In these efforts, we observed and herein report that Sushi Containing Domain 2 (SUSD2) is a novel and consistent marker for cultured human cardiac fibroblast and myofibroblasts.
Copyright © 2021. Published by Elsevier Inc.
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Perioperative high-density lipoproteins, oxidative stress, and kidney injury after cardiac surgery.
J Lipid Res2021 Jan;():100024. doi: S0022-2275(21)00004-3.
Smith Loren E, Smith Derek K, Yancey Patricia G, Kon Valentina, Remaley Alan T, Billings Frederic T, Linton MacRae F,
Abstract
Oxidative stress promotes acute kidney injury (AKI). Higher concentrations of HDL cholesterol are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle size and number, paraoxonase-1 activity, and isofuran concentrations in 75 patients who developed AKI and 75 matched control patients. Higher preoperative concentrations of HDL particles were associated with lower odds of AKI (OR: 0.80; 95% CI, 0.71-0.91; p=0.001), higher paraoxonase-1 activity (R=0.36, p<0.001), and lower plasma concentrations of isofurans immediately after surgery (p=0.02). Similarly, higher preoperative small HDL particle concentrations were associated with less AKI, higher paraoxonase-1 activity, and lower isofuran concentrations. Circulating HDL particle concentrations changed rapidly during the perioperative period. Higher intraoperative particle losses were associated with lower odds of AKI (OR: 0.79; 95% CI 0.67-0.93; p=0.005), and increased paraoxonase-1 activity strengthened this association (p=0.006). Intraoperative particle loss was also associated with decreased postoperative isofuran concentrations (p=0.04). Additionally, higher preoperative small HDL particle concentrations and increased intraoperative small particle loss were associated with improved renal function 3-12 months after surgery (p=0.003, 0.01, respectively). In conclusion, a higher preoperative concentration of HDL particles, particularly small particles, is associated with lower oxidative damage and less AKI. Perioperative changes in HDL particle concentrations are also associated with AKI. Small HDL particles may represent a novel modifiable risk factor for AKI.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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Transcatheter Aortic Valve Implantation Outcomes in Chronic Kidney Disease versus End-Stage Kidney Disease.
Am J Cardiol2021 Jan;():. doi: S0002-9149(21)00028-X.
Abushouk Abdelrahman I, Abdelfattah Omar M, Hassanein Mohamed, Saad Anas M, Vipparla Navya, Isogai Toshiaki, Gad Mohamed M, Nakhoul Georges, Krishnaswamy Amar, Kapadia Samir,
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