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Pubblicazioni recenti - cardiac disease
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Kawasaki disease fact check: Myths, misconceptions and mysteries.
J Paediatr Child Health2020 Aug;():. doi: 10.1111/jpc.15101.
Butters Coen, Curtis Nigel, Burgner David P,
Abstract
Kawasaki disease (KD) is an important cause of childhood vasculitis and a common cause of acquired heart disease in children world-wide. The emergence of Paediatric Multisystem Inflammatory Syndrome-Temporally Associated with SARS-CoV-2, a KD-like hyperinflammatory syndrome and the recent death of Dr Tomisaku Kawasaki make this a timely review. Although KD was described by Dr Kawasaki over 50?years ago, there is still no specific diagnostic test and the aetiology remains elusive. This article summarises the latest evidence, highlights important myths and misconceptions and discusses some of the mysteries that surround this disease.
© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).
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Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells.
FASEB J2020 Aug;():. doi: 10.1096/fj.202000454R.
Abu-El-Rub Ejlal, Sareen Niketa, Lester Sequiera Glen, Ammar Hania I, Yan Weiang, ShamsEldeen Asmaa M, Rubinchik Ilan, Moudgil Meenal, Shokry Heba S, Rashed Laila A, Dhingra Sanjiv,
Abstract
Allogeneic mesenchymal stem cells (MSCs) from young and healthy donors are immunoprivileged and have the potential to treat numerous degenerative diseases. However, recent reviews of clinical trials report poor long-term survival of transplanted cells in the recipient that turned down the enthusiasm regarding MSC therapies. Increasing evidence now confirm that though initially immunoprivileged, MSCs eventually become immunogenic after transplantation in the ischemic or hypoxic environment of diseased tissues and are rejected by the host immune system. We performed in vitro (in rat and human cells) and in vivo (in a rat model) investigations to understand the mechanisms of the immune switch in the phenotype of MSCs. The immunoprivilege of MSCs is preserved by the absence of cell surface immune antigen, major histocompatibility complex II (MHC-II) molecule. We found that the ATPase subunit of 19S proteasome "Sug1" regulates MHC-II biosynthesis in MSCs. Exposure to hypoxia upregulates Sug1 in MSCs and its binding to class II transactivator (CIITA), a coactivator of MHC-II transcription. Sug1 binding to CIITA in hypoxic MSCs promotes the acetylation and K63 ubiquitination of CIITA leading to its activation and translocation to the nucleus, and ultimately MHC-II upregulation. In both rat and human MSCs, knocking down Sug1 inactivated MHC-II and preserved immunoprivilege even following hypoxia. In a rat model of myocardial infarction, transplantation of Sug1-knockdown MSCs in ischemic heart preserved immunoprivilege and improved the survival of transplanted cells. Therefore, the current study provides novel mechanisms of post-transplantation loss of immunoprivilege of MSCs. This study may help in facilitating better planning for future clinical trials.
© 2020 Federation of American Societies for Experimental Biology.
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Incidence of pre-eclampsia and other perinatal complications among women with congenital heart diseases: systematic review and meta-analysis.
Ultrasound Obstet Gynecol2020 Aug;():. doi: 10.1002/uog.22174.
Martinez-Portilla R J, Poon L C, Benitez-Quintanilla L, Sotiriadis A, Lopez M, Lip-Sosa D L, Figueras F,
Abstract
OBJECTIVE:
It has recently been proposed that preeclampsia (PE) may be originating from maternal cardiac maladaptation rather than primary placental insult. As congenital heart disease (CHD) is associated with reduced adaptation to the hemodynamic needs of pregnancy, it is hypothesized that women with CHD would have an increased risk of PE. The aim of this study was to investigate the risk of PE in women with CHD.
DATA SOURCES:
A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, Chinese, or German with no time restrictions, using databases such as PubMed, Web of Science, and Scopus.
STUDY ELIGIBILITY CRITERIA:
Randomized controlled trials and observational studies (prospective and retrospective cohorts) of pregnant women with a history of CHD were selected.
STUDY APPRAISAL AND SYNTHESIS METHODS:
The main outcome was the incidence of PE (including eclampsia and HELLP syndrome). For quality assessment, two reviewers independently assessed the risk of bias of the included studies. For the meta-analysis, the incidence of PE in completed pregnancies (those beyond 20?weeks' gestation) was calculated using a single-proportion analysis by random-effects modeling (weighted by inverse-variance). Heterogeneity between studies was assessed using the X (Cochrane Q), H, and I statistics. Subgroup analyses were performed as well as meta-regression to explain the influence of several covariates on the pooled results.
RESULTS:
After the systematic review, a total of 33 studies were retained for the meta-analysis, comprising 40,449 women with CHD and a total of 40,701 completed pregnancies. The incidence of PE was 3.1% (95% CI: 2.2-4.0%), true-effect heterogeneity was 93% by I , and no publication bias was found. No differences were found in the incidence of PE between studies including cyanotic CHD vs. studies without cyanotic CHD (2.5% [95% CI: 1.6%-3.4%] vs. 3.8% [95% CI: 2.4%-5.2%]; p=0.112). The meta-regression analysis showed that the only cofactor significantly influencing the incidence of PE was the incidence of aortic stenosis reported in each article; articles with a higher incidence of aortic stenosis had a higher incidence of PE (estimate: 0.0005; p=0.038).
CONCLUSIONS:
In women with CHD, we have failed to demonstrate an incidence of PE above the expected baseline, an observation that disagrees with the theory of the cardiac origin of PE. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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Cardiovascular risk after adjuvant trastuzumab in early breast cancer: an Italian population-based cohort study.
Oncologist2020 Aug;():. doi: 10.1634/theoncologist.2020-0216.
Franchi Matteo, Trama Annalisa, Merlo Ivan, Minicozzi Pamela, Tarantini Luigi, Garau Donatella, Kirchmayer Ursula, Di Martino Mirko, Romero Marilena, De Carlo Ilenia, Scondotto Salvatore, Apolone Giovanni, Corrao Giovanni, ,
Abstract
BACKGROUND:
Although trastuzumab (T) represents the standard of care for the adjuvant treatment of HER-2 positive early-stage breast cancer, contrasting results are available about the cardiac toxicity associated to its use. We conducted a multiregional population-based cohort investigation aimed to assess both the short- and long-term cardiovascular (CV) outcomes in women with early-breast cancer treated with T-based or standard adjuvant chemotherapy (CT).
PATIENTS AND METHODS:
We used healthcare utilization databases of six Italian regions, overall accounting for 42% of the Italian population. The study cohort was made by all women surgically treated for breast cancer who started a first-line adjuvant T-based or CT treatment. Patients treated with T were 1:2 matched to those treated with CT based on date of treatment start, age and presence of CV risk factors. Short- and long-term CV outcomes (heart failure and cardiomyopathy) were measured, respectively, after one year and at the end of follow-up.
RESULTS:
Among 28,599 women who met the inclusion criteria, 6,208 T users where matched to 12,416 CT users. After a mean follow-up of 5.88?years, short- and long-term cumulative CV risk were 0.8% and 2.6% in patients treated with T and 0.2% and 2.8% in those treated with CT, respectively. Adjusted hazard ratios were 4.6 (95% CI: 2.6 to 8.0) for short-term and 1.2 (0.9 to 1.6) for long-term CV risk.
DISCUSSION:
In our large real-world investigation, T-associated cardiotoxicity was limited to the treatment period. The addition of T to adjuvant CT did not result in long-term worsening of CV events.
IMPLICATION FOR PRACTICE:
Adjuvant trastuzumab-based chemotherapy represents the backbone therapy in HER2 positive early breast cancer patients. Although well tolerated, cardiovascular events can manifest during or after therapy due to treatment-related toxicities. In our wide multicentre and unselected cohort, long-term symptomatic cardiotoxicity was low and limited to the treatment period. The findings suggest that developing tools that would be adequately able to predict cardiac toxicity at an early stage remains an important area where additional research efforts are needed.
© AlphaMed Press 2020.
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Lung Ultrasound in COVID-19 A Role Beyond the Acute Phase?
J Ultrasound Med2020 Aug;():. doi: 10.1002/jum.15425.
Gaspardone Carlo, Meloni Carlo, Preda Alberto, Romagnolo Davide, Brugliera Luigia, Castellazzi Paola, Tettamanti Andrea, Conte Caterina, Secchi Antonio, Maranta Francesco, Iannaccone Sandro, Cianflone Domenico,
Abstract
OBJECTIVES:
Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2. With the increasing number of improved and discharged patients with COVID-19, the definition of an adequate follow-up strategy is needed. The purpose of this study was to assess whether lung ultrasound (LUS) is an effective indicator of subclinical residual lung damage in patients with COVID-19 who meet discharge criteria.
METHODS:
We prospectively enrolled 70 consecutive patients with COVID-19 who had a prolonged hospitalization with inpatient rehabilitation between April 6 and May 22, 2020. All of the patients underwent an LUS evaluation at discharge. Data of patients with more severe disease during the acute phase (ie, required ventilatory support) were compared to those of patients with milder disease.
RESULTS:
Among the 70 patients with COVID-19 (22 women and 48 men; mean age?±?SD, 68?±?13?years), the LUS score before discharge was still frankly pathologic and higher in patients who had more severe disease during the acute phase compared to patients with milder disease (median [interquartile range], 8.0 [5.5-13.5] versus 2.0 [1.0-7.0]; P?
CONCLUSIONS:
Lung ultrasound can identify the persistence of subclinical residual lung damage in patients with severe COVID-19 even if they meet discharge criteria. Considering the low cost, easy application, and lack of radiation exposure, LUS seems the ideal tool to be adopted in outpatient and primary care settings for the follow-up of patients with COVID-19.
© 2020 American Institute of Ultrasound in Medicine.
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Preoperative soluble VCAM-1 contributes to predict late mortality after coronary artery surgery.
Clin Cardiol2020 Aug;():. doi: 10.1002/clc.23443.
Corbalan Ramon, Garcia Mauricio, Garrido-Olivares Luis, Garcia Lorena, Perez Gonzalo, Mellado Rosemarie, Zalaquett Ricardo, Chiong Mario, Quitral Jorge, Lavandero Sergio,
Abstract
BACKGROUND:
Soluble vascular cell adhesion molecule-1 has been associated with long-term cardiovascular mortality in patients with stable coronary artery disease and to the development of new atrial fibrillation in subjects with cardiovascular risk factors but no evidence of cardiac disease.
HYPOTHESIS:
Preoperative soluble vascular cell adhesion molecule-1 predicts the risk of future all-cause death and cardiovascular death among patients submitted to elective coronary artery bypass surgery.
METHODS:
From a cohort of 312 patients who underwent elective coronary artery bypass surgery prospectively followed for a median of 6.7?years, we evaluated the prognostic role of preoperative soluble vascular cell adhesion molecule-1, inflammatory markers, CHA2DS2-VASc score and development of postoperative atrial fibrillation (POAF). Univariable and multivariable Cox regression analyses were performed to establish an association of these parameters with long term all-cause death and cardiovascular death.
RESULTS:
During 2112 person-years of follow-up, we observed 41 deaths, 10 were cardiovascular deaths. Independently increased levels of preoperative soluble vascular cell adhesion molecule-1, POAF, and CHA2DS2-VASc score were associated with all-cause mortality. After multivariate adjustment, elevated preoperative soluble vascular cell adhesion molecule-1 and POAF were the only independent predictors of all-cause death. Also, preoperative soluble vascular cell adhesion molecule-1, POAF, and CHA2DS2-VASc score resulted in being independent predictors of cardiovascular mortality.
CONCLUSIONS:
Increased circulating levels of preoperative soluble vascular cell adhesion molecule-1, together with POAF and CHA2DS2-VASc score, were significantly associated with future all-cause death and cardiovascular death among patients submitted to coronary artery bypass surgery.
© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.
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Angiotensin-Converting Enzyme Inhibition: Beyond Blood Pressure Control-The Role of Zofenopril.
Adv Ther2020 Aug;():. doi: 10.1007/s12325-020-01455-2.
Borghi Claudio, Omboni Stefano,
Abstract
The extensive use of angiotensin-converting enzyme inhibitors (ACEIs) as antihypertensive agents and the huge amount of data collected in clinical trials and post-marketing studies has allowed the extending of the indication of ACEIs beyond blood pressure control. Current guidelines recommend ACEIs in symptomatic patients with heart failure with reduced ejection fraction to decrease the risk of heart failure hospitalization, and also in patients after acute myocardial infarction (AMI) with ST-elevation with or without post-AMI ventricular dysfunction. Analyzing the association between the choice of an ACEI after AMI with the risk of mortality and re-infarction, a class effect, rather than the superiority of some agents, has been described. The focus of this review is centered on the role of ACEIs in addition to and beyond blood pressure control. It summarizes clinical evidence on the use of these agents in cardiovascular diseases, with a specific interest in the experience with zofenopril, which presents a peculiar pharmacological profile that may contribute to additional clinical benefits in some identifiable populations of patients. Indeed, the presence of a sulfhydryl group in its structure confers on zofenopril high anti-oxidant and anti-ischemic properties involving the activation of the HS system, resulting in a cardioprotective effect. The efficacy and safety of zofenopril have been extensively evaluated and proved in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) program in numerous clinical settings. The pharmacological features and ancillary characteristics of zofenopril with potent cardioprotective effects seem to differentiate it from other ACEIs and to confer further benefits to patients.
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Pistacia integerrima alleviated Bisphenol A induced toxicity through Ubc13/p53 signalling.
Mol Biol Rep2020 Aug;():. doi: 10.1007/s11033-020-05706-x.
Ishtiaq Ayesha, Bakhtiar Attia, Silas Erica, Saeed Javeria, Ajmal Sidra, Mushtaq Iram, Ali Tahir, Wahedi Hussain M, Khan Wajiha, Khan Uzma, Anees Mariam, Sultan Aneesa, Murtaza Iram,
Abstract
Exposure to environmental toxicants such as Bisphenol A (BPA) has raised serious health issues globally particularly in developing countries. It is ubiquitously used in the manufacturing of canned food and feeding bottles. BPA generated reactive oxygen species can lead to several diseases including cardiotoxicity. However, the endpoints stimulated in BPA cardiotoxicity yet need to be investigated. The current study was aimed to investigate the underlying molecular pathways which may contribute in revealing the protective effects of Pistacia integerrima against BPA induced oxidative stress. The dose of 100 µg/kg BW of BPA, 200 mg/kg BW P. integerrima, and 4 mg/kg BW melatonin was administered to Sprague Dawley rats. Present results of western blotting and qRT-PCR showed the increased expression of p53, PUMA and Drp1, while downregulation of Ubc13 in heart tissues of BPA treated group whereas the levels were reversed upon treatment with P. integerrima. The role of BPA in heart tissue apoptosis was further confirmed by the increased level of P-p53, cytochrome C and disrupted cellular architecture whereas the P. integerrima has shown its ameliorative potential by mitigating the adverse effects of BPA. Moreover, the oxidant, antioxidant, lipid, and liver markers profile has also revealed the therapeutic potential of P. integerrima by maintaining the levels in the normal range. However, melatonin has also manifested the normalized expression of apoptotic markers, biochemical markers, and tissue architecture. Conclusively, the data suggest that P. integerrima may be a potential candidate for the treatment of BPA induced toxicity by neutralizing the oxidative stress through Ubc13/p53 pathway.
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Sex-Related Differences in Dilated Cardiomyopathy with a Focus on Cardiac Dysfunction in Oncology.
Curr Cardiol Rep2020 Aug;22(10):102. doi: 10.1007/s11886-020-01377-z.
D'Amario Domenico, Camilli Massimiliano, Migliaro Stefano, Canonico Francesco, Galli Mattia, Arcudi Alessandra, Montone Rocco Antonio, Borovac Josip Andjelo, Crea Filippo, Savarese Gianluigi,
Abstract
PURPOSE OF REVIEW:
The aim of this report is to describe the main aspects of sex-related differences in non-ischemic dilated cardiomyopathies (DCM), focusing on chemotherapy-induced heart failure (HF) and investigating the possible therapeutic implications and clinical management applications in the era of personalized medicine.
RECENT FINDINGS:
In cardio-oncology, molecular and multimodality imaging studies confirm that sex differences do exist, affecting the therapeutic cardioprotective strategies and, therefore, the long-term outcomes. Interestingly, compelling evidences suggest that sex-specific characteristics in drug toxicity might predict differences in the therapeutic response, most likely due to the tangled interplay between cancer and HF, which probably share common underlying mechanisms. Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestations, from sex-determined differential gene expression to sex hormone interaction with their receptors in the heart. Non-ischemic DCM is an umbrella definition that incorporates several etiologies, including chemotherapy-induced cardiomyopathies. The role of sex as a risk factor for cardiotoxicity is poorly explored. However, understanding the various features of disease manifestation and outcomes is of paramount importance for a prompt and tailored evaluation.
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The Role of Echocardiography in the Cancer Patient.
Curr Cardiol Rep2020 Aug;22(10):103. doi: 10.1007/s11886-020-01373-3.
Palaskas Nicolas L, Lopez-Mattei Juan,
Abstract
PURPOSE OF REVIEW:
To review the uses of echocardiography in patients with cancer and how it has expanded beyond the typical monitoring of systolic function during potentially cardiotoxic cancer therapeutics.
RECENT FINDINGS:
In addition to myocardial strain imaging being a predictor of subsequent left ventricular dysfunction, it can be used for pattern recognition to help identify patients with cardiac amyloidosis or Takotsubo cardiomyopathy. Echocardiography is essential for diagnosis and planning of intervention for aortic stenosis in radiation-induced valvular disease, for which transcutaneous aortic valve replacement that gives many cancer patients that are not surgical candidates an option for treatment. The safety of transesophageal echocardiography has recently been demonstrated in patients with cancer with thrombocytopenia and depleted white blood cell counts who are at increased risk of endocarditis. Echocardiography is an essential tool for evaluating common conditions in cancer patients such as pericardial disease, radiation-induced heart disease, and intracardiac tumors-with specific uses of specialized echocardiography techniques such as deformation imaging, transesophageal echocardiography, and point-of-care ultrasound.
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Icosapent Ethyl: Niche Drug or for the Masses?
Curr Cardiol Rep2020 Aug;22(10):104. doi: 10.1007/s11886-020-01356-4.
Bazarbashi Najdat, Miller Michael,
Abstract
PURPOSE OF REVIEW:
Despite achieving optimal levels of low-density lipoprotein cholesterol (LDL-C) with statins, the risk of atherosclerotic cardiovascular disease (ASCVD) persists. The purpose of this review is to outline the effects of icosapent ethyl (IPE), an ultra-purified eicosapentaenoic acid (EPA) on ASCVD risk assessment.
RECENT FINDINGS:
Many studies have shown that elevated triglycerides (TG) contribute to increased risk of ASCVD. However, the only outcomes trial to date to demonstrate a benefit in patients with elevated TG beyond its lipid-lowering properties is REDUCE-IT. Yet, despite IPE demonstrating a relatively modest reduction in TG (~?20%), there was a 25% relative risk reduction in the primary endpoint and a 30% reduction in total events. Sub-analysis of REDUCE-IT also showed a statically significant decrease in cardiac arrest (HR 0.52 (0.31-0.86), p?=?0.01) and sudden cardiac death (HR 0.69 (0.50-0.96), p?=?0.03). The CVD benefits observed in REDUCE-IT coincide with on-treatment EPA levels. Icosapent ethyl's multiple bioactive properties contribute to CVD risk reduction beyond TG lowering effects. Because patients with a REDUCE-IT-like profile are highly prevalent in the USA and abroad, IPE should not be viewed as a niche drug, but rather part of a proven armamentarium that deserves widespread use in appropriate patients at elevated ASCVD risk.
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Review of Transthyretin Silencers, Stabilizers, and Fibril Removal Agents in the Treatment of Transthyretin Cardiac Amyloid.
Curr Cardiol Rep2020 Aug;22(10):106. doi: 10.1007/s11886-020-01374-2.
Hough Augustus, Wearden Jessica, de Almeida Kristen, Kaiser Stephanie,
Abstract
PURPOSE OF REVIEW:
To provide a functional review for practicing clinicians on the current and emerging treatment considerations for transthyretin (TTR) cardiac amyloidosis (ATTR-CA).
RECENT FINDINGS:
Current treatment considerations are characterized as those silencing TTR translation, stabilizing TTR tetramers, and disrupting amyloid fibril deposition. Historically considered a rare disease state, ATTR-CA is increasingly recognized as an important mediator of heart failure morbidity and mortality. The emergence of widely available therapies for ATTR-CA has developed hope for patients where little was previously present. Thus, it is important that all cardiology clinicians have a functional understanding of the disease state and treatment options. This review will discuss agents within each of the above classes with expanded discussion on tafamidis given its favorable efficacy, safety, and availability. ATTR-CA diagnostic considerations are reviewed with regard to the identification of potential tafamidis candidates, and practical economic considerations are also reviewed.
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Association between right-sided cardiac function and ultrasound-based pulmonary congestion on acutely decompensated heart failure: findings from a pooled analysis of four cohort studies.
Clin Res Cardiol2020 Aug;():. doi: 10.1007/s00392-020-01724-8.
Kobayashi Masatake, Gargani Luna, Palazzuoli Alberto, Ambrosio Giuseppe, Bayés-Genis Antoni, Lupon Josep, Pellicori Pierpaolo, Pugliese Nicola Riccardo, Reddy Yogesh N V, Ruocco Gaetano, Duarte Kevin, Huttin Olivier, Rossignol Patrick, Coiro Stefano, Girerd Nicolas,
Abstract
BACKGROUND:
Right ventricular (RV) dysfunction and RV-pulmonary artery (PA) uncoupling are associated with the development of pulmonary congestion during exercise. However, there is limited information regarding the association between these right-sided cardiac parameters and pulmonary congestion in acutely decompensated heart failure (HF).
METHODS:
We performed an individual patient meta-analysis from four cohort studies of hospitalized patients with HF who had available lung ultrasound (B-lines) data on admission and/or at discharge. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), RV-PA coupling was defined as the ratio of TAPSE to PA systolic pressure (PASP).
RESULTS:
Admission and discharge cohort included 319 patients (75.8?±?10.1 years, 46% women) and 221 patients (77.9?±?9.0 years, 47% women), respectively. Overall, higher TAPSE was associated with higher ejection fraction, lower PASP, b-type natriuretic peptide and B-line counts. By multivariable analysis, worse RV function or RV-PA coupling was associated with higher B-line counts on admission and at discharge, and with a less reduction in B-line counts from admission to discharge. Higher B-line counts at discharge were associated with a higher risk of the composite of all-cause mortality and/or HF re-hospitalization [adjusted-HR 1.13 (1.09-1.16), p?
CONCLUSIONS:
In patients with acutely decompensated HF, impaired RV function and RV-PA coupling were associated with severe pulmonary congestion on admission, and less resolution of pulmonary congestion during hospital stay. Worse prognosis related to residual pulmonary congestion was enhanced in patients with RV dysfunction. TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure.
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The Cardiorenal Syndrome: Mechanistic Insights and Prognostication with Soluble Biomarkers.
Curr Cardiol Rep2020 Aug;22(10):114. doi: 10.1007/s11886-020-01360-8.
Seliger Stephen,
Abstract
PURPOSE OF REVIEW:
To characterize and interpret recent studies of biomarkers of cardiorenal syndrome.
RECENT FINDINGS:
Recent studies have questioned the mechanisms and significance of moderate worsening renal function (WRF) in patients with acute heart failure. In the setting of successful decongestion, WRF may not predict cardiorenal morbidity. Cardiac-specific biomarkers including cardiac troponins and natriuretic peptides are highly prognostic in acute and chronic HF patients with kidney impairment, and serial changes in these markers during hospitalization are also predictive of longer-term adverse outcomes. These markers also predict new HF in patients with established chronic kidney disease (CKD). The role of kidney tubular injury markers in acute HF remains controversial, with inconsistent associations with short- and long-term cardiorenal outcomes. Many cases of WRF in acute HF are not characterized by a clear pattern of renal tubular injury. Cardiac-specific and renal-specific biomarkers may provide mechanistic and prognostic information in cardiorenal syndromes.
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Paeonol suppresses the effect of ox-LDL on mice vascular endothelial cells by regulating miR-338-3p/TET2 axis in atherosclerosis.
Mol Cell Biochem2020 Aug;():. doi: 10.1007/s11010-020-03865-w.
Yu Yunfu, Yan Rui, Chen Xiaozhen, Sun Tao, Yan Jifeng,
Abstract
Atherosclerosis is the common vascular disease. Vascular smooth muscle cell proliferation and vascular endothelial cell (VEC) dysfunction are involved in the causes of atherosclerosis. And oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cells (VECs) are suitable models for studying atherosclerosis development. Paeonol was reported to repress ox-LDL-induced VEC progression. However, its detailed mechanism was not fully reported. MicroRNAs (miRNAs) acted as regulators in multiple diseases. Previous findings found that microRNA-338-3p (miR-338-3p) was overexpressed in Atherosclerosis process. However, the function and underlying mechanism of miR-338-3p in ox-LDL-treated VECs needed to be elucidated. The purpose of this research was to reveal the role of miR-338-3p in paeonol-regulated ox-LDL-induced VEC progression. Cell counting kit-8 (CCK-8) and flow cytometry were employed to determine cell viability and apoptosis, respectively. Moreover, the levels of IL-6 and IL-1? were analyzed using enzyme-linked immunosorbent assay, as well as the contents of reactive oxygen species, lactate dehydrogenase, and malonic dialdehyde were investigated using related kits. Furthermore, quantitative real-time polymerase chain reaction was carried out to determine the expression of miR-338-3p. Western blot assay was conducted to detect the level of tet methylcytosine dioxygenase 2 (TET2). Besides, the interaction between miR-338-3p and TET2 was predicted by DIANA, and then confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. Ox-LDL repressed mice VEC viability, and promoted apoptosis, inflammatory response, and oxidative injury. Paeonol inhibited the effect of ox-LDL on the growth of the VECs. Furthermore, paeonol regulated VEC development via downregulating miR-338-3p expression. Interestingly, miR-338-3p targeted TET2 and inhibited TET2 expression. MiR-338-3p modulated ox-LDL-treated VEC growth through suppressing TET2 expression. We demonstrated that paeonol attenuated the effect of ox-LDL on the development of mice VECs via modulating miR-338-3p/TET2 axis, providing a theoretical basis for the treatment of AS.
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Presence of purpura is related to active inflammation in association with IL-5 in eosinophilic granulomatosis with polyangiitis.
Rheumatol Int2020 Aug;():. doi: 10.1007/s00296-020-04672-8.
Kataoka Hiroshi, Tomita Tomoko, Kondo Makoto, Mukai Masaya,
Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a relatively rare necrotizing vasculitis that causes asthma, nasal involvement, peripheral nerve disturbance, renal disorder, and cutaneous lesions like purpura and is characterized by eosinophil infiltration into the damaged tissue. Purpura is the most common cutaneous lesion, but it remains unknown whether this skin lesion is associated with disease activity of EGPA and laboratory data including interleukin (IL)-5, a target cytokine of this disease. We conducted a search of our hospital electronic records for cases of EGPA from the last 10 years. Symptoms related to EGPA (fever, asthma, nasal and cutaneous manifestations, neuropathy), the Birmingham Vasculitis Activity Score (BVAS), and laboratory parameters, such as eosinophil count, urinalysis, antineutrophil cytoplasmic antibody (ANCA), CRP, IgE and IL-5, before and during treatment were compared among the eligible cases. A total of 28 EGPA patients (21 females and 7 males) were selected. Almost all developed peripheral neuropathy. Fever occurred in 25%, nasal symptoms in 38.1% and purpura in 44%. Glomerulonephritis developed in 7.7%. One patient had cardiac involvement (3.6%). The laboratory data showed a marked increase in peripheral eosinophil count, CRP, serum IgE and serum IL-5. ANCA was positive in 15.4%. In the univariate analysis, presence of purpura was associated with increased CRP and IL-5, and high BVAS score. Multivariate analysis revealed a robust relationship between purpura and CRP. Our findings showed that presence of purpura was associated with increased CRP and IL-5, and high disease activity in EGPA.
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The clinical characteristics and outcomes of heart failure patient with chronic obstructive pulmonary disease from the Japanese community-based registry.
Heart Vessels2020 Aug;():. doi: 10.1007/s00380-020-01675-0.
Takabayashi Kensuke, Terasaki Yuka, Okuda Miyuki, Nakajima Osamu, Koito Hitoshi, Kitamura Tetsuhisa, Kitaguchi Shouji, Nohara Ryuji,
Abstract
Both heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common diseases, but few studies have assessed the relationship between COPD and outcomes in patients with acute HF, especially in relation to age or ejection fraction (EF). The Kitakawachi Clinical Background and Outcome of Heart Failure Registry was a prospective, multicenter, community-based cohort and enrolled a total of 1,102 patients with acute HF between 2015 and 2017 in this study. The primary endpoint was defined as a composite endpoint that included all-cause mortality and hospitalization for HF. We stratified patients into two groups: those aged???80 years (elderly) and?
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Probenecid Improves Cardiac Function in Subjects with a Fontan Circulation and Augments Cardiomyocyte Calcium Homeostasis.
Pediatr Cardiol2020 Aug;():. doi: 10.1007/s00246-020-02427-7.
Rubinstein Jack, Woo Jessica G, Garcia Anastacia M, Alsaied Tarek, Li Jia, Lunde Per Kristian, Moore Ryan A, Laasmaa Martin, Sammons Amanda, Mays Wayne A, Miyamoto Shelley D, Louch William E, Veldtman Gruschen R,
Abstract
Subjects with functionally univentricular circulation who have completed staged single ventricle palliation, with the final stage culminating in the Fontan procedure, are often living into adulthood. However, high morbidity and mortality remain prevalent in these patients, as diastolic and systolic dysfunction of the single systemic ventricle are linked to Fontan circulatory failure. We presently investigated the effects of probenecid in post-Fontan patients. Used for decades for the treatment of gout, probenecid has been shown in recent years to positively influence cardiac function via effects on the Transient Receptor Potential Vanilloid 2 (TRPV2) channel in cardiomyocytes. Indeed, we observed that probenecid improved cardiac function and exercise performance in patients with a functionally univentricular circulation. This was consistent with our findings from a retrospective cohort of patients with single ventricle physiology where TRPV2 expression was increased. Experiments in isolated cardiomyocytes associated these positive actions to augmentation of diastolic calcium homeostasis.
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Self-reported difficulty initiating sleep and early morning awakenings are associated with nocturnal diastolic non-dipping in older white Swedish men.
Sci Rep2020 Aug;10(1):13355. doi: 10.1038/s41598-020-70399-y.
Tan Xiao, Lind Lars, Ingelsson Martin, Sundström Johan, Cedernaes Jonathan, Benedict Christian,
Abstract
Chronically blunted nocturnal blood pressure (BP) dipping has been shown to increase the future risk of cardiovascular diseases. In the present cross-sectional study, we investigated whether self-reported insomnia symptoms were associated with an altered 24-h BP profile and blunted nocturnal BP dipping (night-to-day BP ratio >?0.90) in older men. For the analysis, we used 24-h ambulatory blood pressure data and reports of insomnia symptoms (difficulty initiating sleep, DIS; and early morning awakenings, EMA) from 995 Swedish men (mean age: 71 years). Compared to men without DIS, those reporting DIS (10% of the cohort) had a higher odds ratio of diastolic non-dipping (1.85 [1.15, 2.98], P?=?0.011). Similarly, men who reported EMA (19% of the cohort) had a higher odds ratio of diastolic non-dipping than those without EMA (1.57 [1.09, 2.26], P?=?0.015). Despite a slightly higher nocturnal diastolic BP among men with EMA vs. those without EMA (+?1.4 mmHg, P?=?0.042), no other statistically significant differences in BP and heart rate were found between men with and those without insomnia symptoms. Our findings suggest that older men reporting difficulty initiating sleep or early morning awakenings may have a higher risk of nocturnal diastolic non-dipping. Our findings must be replicated in larger cohorts that also include women.
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Epsin-mediated degradation of IP3R1 fuels atherosclerosis.
Nat Commun2020 Aug;11(1):3984. doi: 10.1038/s41467-020-17848-4.
Dong Yunzhou, Lee Yang, Cui Kui, He Ming, Wang Beibei, Bhattacharjee Sudarshan, Zhu Bo, Yago Tadayuki, Zhang Kun, Deng Lin, Ouyang Kunfu, Wen Aiyun, Cowan Douglas B, Song Kai, Yu Lili, Brophy Megan L, Liu Xiaolei, Wylie-Sears Jill, Wu Hao, Wong Scott, Cui Guanglin, Kawashima Yusuke, Matsumoto Hiroyuki, Kodera Yoshio, Wojcikiewicz Richard J H, Srivastava Sanjay, Bischoff Joyce, Wang Da-Zhi, Ley Klaus, Chen Hong,
Abstract
The epsin family of endocytic adapter proteins are widely expressed, and interact with both proteins and lipids to regulate a variety of cell functions. However, the role of epsins in atherosclerosis is poorly understood. Here, we show that deletion of endothelial epsin proteins reduces inflammation and attenuates atherosclerosis using both cell culture and mouse models of this disease. In atherogenic cholesterol-treated murine aortic endothelial cells, epsins interact with the ubiquitinated endoplasmic reticulum protein inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), which triggers proteasomal degradation of this calcium release channel. Epsins potentiate its degradation via this interaction. Genetic reduction of endothelial IP3R1 accelerates atherosclerosis, whereas deletion of endothelial epsins stabilizes IP3R1 and mitigates inflammation. Reduction of IP3R1 in epsin-deficient mice restores atherosclerotic progression. Taken together, epsin-mediated degradation of IP3R1 represents a previously undiscovered biological role for epsin proteins and may provide new therapeutic targets for the treatment of atherosclerosis and other diseases.
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