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Pubblicazioni recenti - cardiac disease
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Current and future trial design in refractory cardiogenic shock.
Eur J Heart Fail2023 Mar;():. doi: 10.1002/ejhf.2838.
Arrigo Mattia, Blet Alice, Morley-Smith Andrew, Aissaoui Balanant Nadia, Baran David A, Bayes-Genis Antoni, Chioncel Ovidiu, Desch Steffen, Karakas Mahir, Moller Jacob Eifer, Poess Janine, Price Susanna, Zeymer Uwe, Mebazaa Alexandre,
Abstract
Cardiogenic shock is a life-threatening syndrome of peripheral hypoperfusion and organ dysfunction due to primary cardiac disease. Few adequately designed randomized clinical trials provide guidance on the optimal management strategies, which frequently includes vasoactive drugs, circulatory and ventilatory support, and reversal of any underlying cause, including coronary revascularization in case of acute myocardial infarction. Management is largely based on experience rather than evidence-based recommendations and patient outcomes remain poor. Particular attention is currently given to refractory patients (i.e., not responding to medical treatment) with a growing number of studies investigating various modalities of mechanical circulatory support. This consensus document summarizes the output from the third Critical Care Clinical Trialists Workshop, where a group of experts convened to discuss, debate, and reflect on approaches related to trials in refractory cardiogenic shock, to provide recommendations for the design of future trials. Invited participants included clinical trialists, clinicians (including cardiologists, intensive care specialists, anaesthesiologists, and cardiac surgeons), epidemiologists, patient representatives, regulators from the United States and Europe, United States federal grant managers, and industry representatives. Special attention is given to current and future definitions of cardiogenic shock including refractory states, recent and ongoing clinical trials in refractory cardiogenic shock and future directions in light of the most recent literature.
This article is protected by copyright. All rights reserved.
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Patient after treatment of Hodgkin's lymphoma: A typical? cardiological patient. Author's reply.
Kardiol Pol2023 ;81(3):316-317. doi: 10.33963/KP.a2023.0076.
St?pie? Konrad, Del Carmen Yika Alicia, Bilecki Krzysztof, Furczy?ski Jakub, Nowak Karol, St?pie? Adam, Nessler Jadwiga, Zalewski Jaros?aw, Konduracka Ewa,
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Inflammatory biomarkers in assessing severity and prognosis of immune checkpoint inhibitor-associated cardiotoxicity.
ESC Heart Fail2023 Mar;():. doi: 10.1002/ehf2.14340.
Liang Lin, Cui Chanjuan, Lv Dan, Li Yiqun, Huang Liyan, Feng Jiayu, An Tao, Tian Pengchao, Yang Ke, Hu Linjun, Gao Lizhen, Zhang Jian, Zhang Yuhui, Ma Fei, Wang Yanfeng,
Abstract
AIMS:
Inflammatory biomarkers, including CRP, the neutrophil-to-lymphocyte ratio (NLR), and the neutrophil-to-eosinophil ratio (NER), may predict outcomes in cancer. However, their value in immune checkpoint inhibitor (ICI) therapy-associated cardiotoxicity remains elusive. We aimed to characterize the relationship of inflammatory markers with severity of ICI-related cardiotoxicities (iRCs) and prognosis among patients with iRCs.
METHODS:
Patients who were diagnosed with iRCs between January 2019 and December 2021 were retrospectively enrolled and were dichotomized based on iRC severity into low-grade (grade 1-2) vs. high-grade (grade 3-4) groups.
RESULTS:
Forty-seven patients were included. The median time-to-event from first ICI infusion to onset of iRCs was 35 days (IQR: 19.0-65.5 days). When compared with respective baseline values, cardiac biomarkers and inflammatory markers were significantly elevated at onset of iRCs. Compared with low-grade iRCs, NER at iRC onset was significantly increased among patients with high-grade iRCs (Group × Time, P
CONCLUSIONS:
In patients who develop iRCs, NER is significantly elevated at iRC onset, and higher NER correlates with greater iRC severity and higher mortality. Larger datasets are needed to validate these findings.
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Cardiovascular Screening Practices and Statin Prescription Habits in Patients with Psoriasis among Dermatologists, Rheumatologists and Primary Care Physicians.
Acta Derm Venereol2023 Mar;103():adv5087. doi: 10.2340/actadv.v103.5087.
Berna-Rico Emilio, Abbad-Jaime de Aragon Carlota, Garcia-Aparicio Angel, Palacios-Martinez David, Ballester-Martinez Asuncion, Carrascosa Jose-M, De la Cueva Pablo, Anton Cristina, Azcarraga-Llobet Carlos, Garcia-Mouronte Emilio, De Nicolas-Ruanes Belen, Puig Lluis, Jaen Pedro, Mehta Nehal N, Gelfand Joel M, Gonzalez-Cantero Alvaro,
Abstract
Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.
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Fatty liver disease at the basis of cardiac remodelling and increased heart rate: insights from the UK Biobank.
Liver Int -
Prognostic Value of Pentraxin-3 Change After Primary Percutaneous Coronary Intervention in Patients with ST-Segment Elevation Myocardial Infarction.
J Inflamm Res2023 ;16():1255-1266. doi: 10.2147/JIR.S393703.
Li Sheng-Yu, Liu Lei, Wang Ding-Kun, Ding Xiao-Song, Li Wei-Ping, Li Hong-Wei,
Abstract
PURPOSE:
So far, ST-segment elevation myocardial infarction (STEMI) is still the main cause of morbidity and mortality of cardiovascular diseases worldwide. Recent studies showed that pentraxin-3 (PTX3) was related to the early diagnosis and prognosis of coronary heart disease. This study aimed to investigate the dynamical change of PTX3 after primary percutaneous coronary intervention (pPCI) in STEMI patients and its prognostic value.
PATIENTS AND METHODS:
In this prospective cohort study, a total of 350 patients were enrolled. The plasma level of PTX3 was measured at admission, 24-hour and 5-day after pPCI. The primary endpoint was the incidence of major adverse cardiac cerebral events (MACCEs) during 1-year follow-up.
RESULTS:
Compared with the admission, PTX3 levels were significantly increased at 24 hours, and decreased at 5 days after pPCI in the whole cohort. PTX3 levels at these three time points were not significantly different between the patients with and without MACCEs. Notably, the change in PTX3 from admission to post-pPCI 24-hour (?PTX3) was higher in patients with MACCEs (112.83 vs 17.94 ng/dl, P = 0.001). The ROC curves showed that the cut-off value was 29.22 ng/dl and the area under curves was 0.622 (95% CI: 0.554-0.690, p = 0.001). Multivariable cox regression models revealed that the high ?PTX3 group was an independent predictor of MACCEs (adjusted HR = 2.010, 95% CI = 1.280-3.186, p = 0.003). The higher ?PTX3 group had significantly higher incidences of revascularization (HR = 2.094, 95% CI: 1.056-4.150, p = 0.034) and composite MACCEs (HR = 2.219, 95% CI: 1.425-3.454, p
CONCLUSION:
The higher increase of PTX3 level 24-hour after pPCI appeared to have a potential value in independently predicting the incidence of 1-year MACCEs in STEMI patients, especially for coronary revascularization.
© 2023 Li et al.
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Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion.
Cureus2023 Feb;15(2):e35395. doi: 10.7759/cureus.35395.
Hiremath Jagdish, Mohan J C, Hazra Prakash, Sawhney Jp S, Mehta Ashwani, Shetty Sadanand, Oomman Abraham, Shah Mahesh K, Bantwal Ganapathi, Agarwal Rajeev, Karnik Rajiv, Jain Peeyush, Ray Saumitra, Das Sambit, Jadhao Vibhuti, Suryawanshi Sachin, Barkate Hanmant,
Abstract
Lipid-lowering is a central theme in the management of patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH), with statins being currently used as the first-line lipid-lowering agent (LLAs). Bempedoic acid (BA) has been recently approved for lipid management in ASCVD/HeFH patients. This expert opinion paper brings out the essential concept to assess the current place of BA in the Indian population. Here we highlight that the majority of the patients with clinical ASCVD may not be receiving the optimal dose of statin, thereby failing to achieve their lipid targets. The addition of BA to statin results in a significant reduction in low-density lipoprotein cholesterol (LDL-C) along with substantial reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) levels. For patients who do not achieve LDL-C targets, BA can be an effective add-on alternative to choose among non-statin LLAs. BA is a good choice for statin-intolerant cases, especially in combination with ezetimibe. Given the lack of effect of worsening hyperglycemia or any increase in the occurrence of new-onset diabetes, BA can be used without hesitation in patients with diabetes. The small risk of hyperuricemia could be mitigated with appropriate patient selection and monitoring of serum uric acid levels in patients at high risk of hyperuricemia. We believe BA is an excellent non-statin therapy that is efficacious, well-tolerated, and cost-effective for lipid management in ASCVD, HeFH, and statin-intolerant patients in India.
Copyright © 2023, Hiremath et al.
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Clinical meaning of serum trimethylamine oxide, N-terminal-pro-brain natriuretic peptide, hypoxia-inducible factor-1a and left ventricular function and pregnancy outcome in patients with pregnancy-induced hypertension.
J Med Biochem2023 Mar;42(2):265-273. doi: 10.5937/jomb0-37030.
Wu Ying, Wu Yue, Duan Lihong, Xiao Chunhui, Ren Zeya, Liang Yuntai,
Abstract
BACKGROUND:
To figure out the clinical meaning of serum trimethylamine oxide (TMAO), N-terminal-pro-brain natriuretic peptide (NT-proBNP) and hypoxia-inducible factor-1a (HIF-1a) with left ventricular function and pregnancy outcome in patients with pregnancy-induced hypertension.
METHODS:
From January 2018 to October 2020, 117 patients with gestational hypertension were taken as the research objects and grouped into the gestational hypertension (pregnancy-induced hypertension, 55 cases), mild preeclampsia (mild PE, 43 cases) and severe preeclampsia (severe PE, 19 cases) in the light of the severity of the disease. Analysis of the relation of serum TMAO, NT-proBNP and HIF-1a with the severity of disease and cardiac function indexes in patients with gestational hypertension was conducted. All patients were followed up to the end of pregnancy, and the predictive value of serum TMAO, NT-proBNP and HIF-1a on pregnancy outcome in patients was analyzed.
RESULTS:
Serum TMAO and NT-proBNP of patients were elevated, while HIF-1a was reduced with the severity of the disease (P
CONCLUSIONS:
Serum TMAO, NT-proBNP and HIF-1a in patients with gestational hypertension are associated with disease severity and cardiac function, and have predictive and evaluative values for disease severity and pregnancy outcome.
2023 Ying Wu, Yue Wu, Lihong Duan, Chunhui Xiao, Zeya Ren, Yuntai Liang, published by CEON/CEES.
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Understanding the Mechanisms and Treatment of Heart Failure: Quantitative Systems Pharmacology Models with a Focus on SGLT2 Inhibitors and Sex-Specific Differences.
Pharmaceutics2023 Mar;15(3):. doi: 1002.
Ndiaye Jean François, Nekka Fahima, Craig Morgan,
Abstract
Heart failure (HF), which is a major clinical and public health challenge, commonly develops when the myocardial muscle is unable to pump an adequate amount of blood at typical cardiac pressures to fulfill the body's metabolic needs, and compensatory mechanisms are compromised or fail to adjust. Treatments consist of targeting the maladaptive response of the neurohormonal system, thereby decreasing symptoms by relieving congestion. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, which are a recent antihyperglycemic drug, have been found to significantly improve HF complications and mortality. They act through many pleiotropic effects, and show better improvements compared to others existing pharmacological therapies. Mathematical modeling is a tool used to describe the pathophysiological processes of the disease, quantify clinically relevant outcomes in response to therapies, and provide a predictive framework to improve therapeutic scheduling and strategies. In this review, we describe the pathophysiology of HF, its treatment, and how an integrated mathematical model of the cardiorenal system was built to capture body fluid and solute homeostasis. We also provide insights into sex-specific differences between males and females, thereby encouraging the development of more effective sex-based therapies in the case of heart failure.
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Computational Modeling on Drugs Effects for Left Ventricle in Cardiomyopathy Disease.
Pharmaceutics2023 Feb;15(3):. doi: 793.
Tomasevic Smiljana, Milosevic Miljan, Milicevic Bogdan, Simic Vladimir, Prodanovic Momcilo, Mijailovich Srboljub M, Filipovic Nenad,
Abstract
Cardiomyopathy is associated with structural and functional abnormalities of the ventricular myocardium and can be classified in two major groups: hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Computational modeling and drug design approaches can speed up the drug discovery and significantly reduce expenses aiming to improve the treatment of cardiomyopathy. In the SILICOFCM project, a multiscale platform is developed using coupled macro- and microsimulation through finite element (FE) modeling of fluid-structure interactions (FSI) and molecular drug interactions with the cardiac cells. FSI was used for modeling the left ventricle (LV) with a nonlinear material model of the heart wall. Simulations of the drugs' influence on the electro-mechanics LV coupling were separated in two scenarios, defined by the principal action of specific drugs. We examined the effects of Disopyramide and Dygoxin which modulate Ca transients (first scenario), and Mavacamten and 2-deoxy adenosine triphosphate (dATP) which affect changes of kinetic parameters (second scenario). Changes of pressures, displacements, and velocity distributions, as well as pressure-volume (P-V) loops in the LV models of HCM and DCM patients were presented. Additionally, the results obtained from the SILICOFCM Risk Stratification Tool and PAK software for high-risk HCM patients closely followed the clinical observations. This approach can give much more information on risk prediction of cardiac disease to specific patients and better insight into estimated effects of drug therapy, leading to improved patient monitoring and treatment.
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Regulation of Hypoxic-Adenosinergic Signaling by Estrogen: Implications for Microvascular Injury.
Pharmaceuticals (Basel)2023 Mar;16(3):. doi: 422.
Cassavaugh Jessica, Qureshi Nada, Csizmadia Eva, Longhi Maria Serena, Matyal Robina, Robson Simon C,
Abstract
Loss of estrogen, as occurs with normal aging, leads to increased inflammation, pathologic angiogenesis, impaired mitochondrial function, and microvascular disease. While the influence of estrogens on purinergic pathways is largely unknown, extracellular adenosine, generated at high levels by CD39 and CD73, is known to be anti-inflammatory in the vasculature. To further define the cellular mechanisms necessary for vascular protection, we investigated how estrogen modulates hypoxic-adenosinergic vascular signaling responses and angiogenesis. Expression of estrogen receptors, purinergic mediators inclusive of adenosine, adenosine deaminase (ADA), and ATP were measured in human endothelial cells. Standard tube formation and wound healing assays were performed to assess angiogenesis in vitro. The impacts on purinergic responses in vivo were modeled using cardiac tissue from ovariectomized mice. CD39 and estrogen receptor alpha (ER?) levels were markedly increased in presence of estradiol (E2). Suppression of ER? resulted in decreased CD39 expression. Expression of ENT1 was decreased in an ER-dependent manner. Extracellular ATP and ADA activity levels decreased following E2 exposure while levels of adenosine increased. Phosphorylation of ERK1/2 increased following E2 treatment and was attenuated by blocking adenosine receptor (AR) and ER activity. Estradiol boosted angiogenesis, while inhibition of estrogen decreased tube formation in vitro. Expression of CD39 and phospho-ERK1/2 decreased in cardiac tissues from ovariectomized mice, whereas ENT1 expression increased with expected decreases in blood adenosine levels. Estradiol-induced upregulation of CD39 substantially increases adenosine availability, while augmenting vascular protective signaling responses. Control of CD39 by ER? follows on transcriptional regulation. These data suggest novel therapeutic avenues to explore in the amelioration of post-menopausal cardiovascular disease, by modulation of adenosinergic mechanisms.
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Nutritional Status and the Outcomes of Endoscopic Stenting in Benign and Malignant Diseases of Esophagus.
Nutrients2023 Mar;15(6):. doi: 1524.
Dudzic Wojciech, P?atkowski Cezary, Folwarski Marcin, Meyer-Szary Jaros?aw, Ka?mierczak-Siedlecka Karolina, Ekman Marcin, Wojciechowicz Tomasz, Dobosz Marek,
Abstract
BACKGROUND:
Endoscopic stenting (ES) is a widely known method for palliative dysphagia treatment in esophageal strictures. Esophageal cancer is often associated with advanced malnutrition, which may increase the risk of complications of the procedure. The aim of this study was to evaluate complication rates and the impact of nutritional status on the outcomes of ES.
PATIENTS AND METHODS:
A single-center retrospective study was conducted at Copernicus Hospital in Gda?sk, Poland. Adult patients who underwent endoscopic stenting between February 2014 and December 2018 were included. The influence of patient characteristics (age, sex, indications for esophageal stenting, and location of stenosis) and nutritional status (BMI, NRS 2002, GLIM, and dysphagia score) on complication rates and survival were analyzed.
RESULTS:
Eighty-one patients (69% men) were enrolled in the study. In 69%, the indication for ES was malignancy (mainly esophageal cancer). The median dysphagia score significantly decreased from 2.8 to 0.6 after the procedure (
CONCLUSIONS:
Endoscopic stenting is a relatively safe procedure for the palliative treatment of esophageal strictures. Severe malnutrition, although common, does not affect the outcomes of the procedure.
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Selenium, Stroke, and Infection: A Threefold Relationship; Where Do We Stand and Where Do We Go?
Nutrients2023 Mar;15(6):. doi: 1405.
Liampas Andreas, Zis Panagiotis, Hadjigeorgiou Georgios, Vavougios George D,
Abstract
Stroke is currently the second most common cause of death worldwide and a major cause of serious long-term morbidity. Selenium is a trace element with pleotropic effects on human health. Selenium deficiency has been associated with a prothrombotic state and poor immune response, particularly during infection. Our aim was to synthesize current evidence on the tripartite interrelationship between selenium levels, stroke, and infection. Although evidence is contradictory, most studies support the association between lower serum selenium levels and stroke risk and outcomes. Conversely, limited evidence on the role of selenium supplementation in stroke indicates a potentially beneficial effect of selenium. Notably, the relationship between stroke risk and selenium levels is bimodal rather than linear, with higher levels of serum selenium linked to disturbances of glucose metabolism and high blood pressure, morbidities which are, in turn, substrates for stroke. Another such substrate is an infection, albeit forming a bidirectional relationship with both stroke and the consequences of impaired selenium metabolism. Perturbed selenium homeostasis leads to impaired immune fitness and antioxidant capacity, which both favor infection and inflammation; specific pathogens may also contend with the host for transcriptional control of the selenoproteome, adding a feed-forward loop to this described process. Broader consequences of infection such as endothelial dysfunction, hypercoagulation, and emergent cardiac dysfunction both provide stroke substrates and further feed-forward feedback to the consequences of deficient selenium metabolism. In this review, we provide a synthesis and interpretation of these outlined complex interrelationships that link selenium, stroke, and infection and attempt to decipher their potential impact on human health and disease. Selenium and the unique properties of its proteome could provide both biomarkers and treatment options in patients with stroke, infection, or both.
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Soy Consumption and the Risk of Type 2 Diabetes and Cardiovascular Diseases: A Systematic Review and Meta-Analysis.
Nutrients2023 Mar;15(6):. doi: 1358.
Zuo Xinrong, Zhao Rui, Wu Minming, Wan Qianyi, Li Tao,
Abstract
Soy is rich in plant protein, isoflavones, and polyunsaturated fatty acids. To clarify the associations between soy intake and type 2 diabetes (T2D) and cardiovascular diseases (CVDs) events, we performed a meta-analysis and review. A total of 1963 studies met the inclusion criteria, and 29 articles with 16,521 T2D and 54,213 CVDs events were identified by the eligibility criteria. During a follow-up of 2.5-24 years, the risk of T2D, CVDs, coronary heart disease, and stroke in participants with the highest soy consumption decreased by 17% (total relative risk (TRR) = 0.83, 95% CI: 0.74-0.93), 13% (TRR = 0.87, 95% CI: 0.81-0.94), 21% (TRR = 0.79, 95% CI: 0.71-0.88), and 12% (TRR = 0.88, 95% CI: 0.79-0.99), respectively, compared to the lowest sot consumption. A daily intake of 26.7 g of tofu reduced CVDs risk by 18% (TRR = 0.82, 95% CI: 0.74-0.92) and 11.1 g of natto lowered the risk of CVDs by 17% (TRR = 0.83, 95% CI: 0.78-0.89), especially stroke. This meta-analysis demonstrated that soy consumption was negatively associated with the risks of T2D and CVDs and a specific quantity of soy products was the most beneficial for the prevention of T2D and CVDs. This study has been registered on PROSPERO (registration number: CRD42022360504).
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Magnesium Improves Cardiac Function in Experimental Uremia by Altering Cardiac Elastin Protein Content.
Nutrients2023 Mar;15(6):. doi: 1303.
Barros Xoana, Friesen Xenia, Mathias Brandenburg Vincent, Liehn Elisa Anamaria, Steppan Sonja, Kiessling Fabian, Kramann Rafael, Floege Jürgen, Krüger Thilo, Kaesler Nadine,
Abstract
Cardiovascular complications are accompanied by life-threatening complications and represent the major cause of death in patients with chronic kidney disease (CKD). Magnesium is important for the physiology of cardiac function, and its deficiency is common in CKD. In the present study, we investigated the impact of oral magnesium carbonate supplementation on cardiac function in an experimental model of CKD induced in Wistar rats by an adenine diet. Echocardiographic analyses revealed restoration of impaired left ventricular cardiac function in animals with CKD. Cardiac histology and real-time PCR confirmed a high amount of elastin protein and increased collagen III expression in CKD rats supplemented with dietary magnesium as compared with CKD controls. Both structural proteins are crucial in maintaining cardiac health and physiology. Aortic calcium content increased in CKD as compared with tissue from control animals. Magnesium supplementation numerically lowered the increases in aortic calcium content as it remained statistically unchanged, compared with controls. In summary, the present study provides evidence for an improvement in cardiovascular function and aortic wall integrity in a rat model of CKD by magnesium, as evidenced by echocardiography and histology.
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Virtual Screening of Novel 24-Dehydroxysterol Reductase () Inhibitors and the Biological Evaluation of Irbesartan in Cholesterol-Lowering Effect.
Molecules2023 Mar;28(6):. doi: 2643.
Wang Haozhen, Lu Ziyin, Li Yang, Liu Ting, Zhao Linlin, Gao Tianqi, Lu Xiuli, Gao Bing,
Abstract
Hyperlipidemia is a risk factor for the development of fatty liver and cardiovascular diseases such as atherosclerosis and coronary heart disease, and hence, cholesterol-lowering drugs are considered important and effective in preventing cardiovascular diseases. Thus, researchers in the field of new drug development are endeavoring to identify new types of cholesterol-lowering drugs. 3?-hydroxysterol-?(24)-reductase () catalyzes the conversion of desmosterol to cholesterol, which is the last step in the cholesterol biosynthesis pathway. We speculated that blocking the catalytic activity of could be a novel therapeutic strategy for treating hyperlipidemia. In the present study, by virtually screening the DrugBank database and performing molecular dynamics simulation analysis, we selected four potential inhibitor candidates: irbesartan, risperidone, tolvaptan, and conivaptan. All four candidates showed significant cholesterol-lowering activity in HepG2 cells. The experimental mouse model of hyperlipidemia demonstrated that all four candidates improved high blood lipid levels and fat vacuolation in the livers of mice fed with a high-fat diet. In addition, Western blot analysis results suggested that irbesartan reduced cholesterol levels by downregulating the expression of the low-density lipoprotein receptor. Finally, the immune complex activity assay confirmed the inhibitory effect of irbesartan on the enzymatic activity of with its half-maximal inhibitory concentration (IC50) value of 602 nM. Thus, to the best of our knowledge, this is the first study to report that blocking the enzymatic activity of via competitive inhibition is a potential strategy for developing new cholesterol-lowering drugs against hyperlipidemia or multiple cancers. Furthermore, considering that irbesartan is currently used to treat hypertension combined with type 2 diabetes, we believe that irbesartan should be a suitable choice for patients with both hypertension and hyperlipidemia.
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Effect of a Fourth Dose of mRNA Vaccine and of Immunosuppression in Preventing SARS-CoV-2 Breakthrough Infections in Heart Transplant Patients.
Microorganisms2023 Mar;11(3):. doi: 755.
Masetti Marco, Scuppa Maria Francesca, Aloisio Alessio, Giovannini Laura, Borgese Laura, Manno Stefania, Tazza Beatrice, Pascale Renato, Bonazzetti Cecilia, Caroccia Natascia, Sabatino Mario, Spitaleri Giosafat, Viale Pierluigi, Giannella Maddalena, Potena Luciano,
Abstract
Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21-11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT
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Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review.
Metabolites2023 Mar;13(3):. doi: 430.
Nappi Francesco, Avtaar Singh Sanjeet Singh,
Abstract
Endothelial integrity plays a major role in homeostasis and is responsive to the numerous endogenous factors released. While its functional role in vascular tone is well described, its role in the pathophysiology of cardiovascular disease is of interest as a potential therapeutic target. We performed a systematic review to provide an overview of new therapeutic and diagnostic targets for the treatment of coronary artery disease related to endothelial dysfunction. Databases of PubMed, Ovid's version of MEDLINE, and EMBASE were interrogated with appropriate search terms. Inclusion criteria have been met by 28 studies that were included in the final systematic review. We identified inflammation, pulmonary hypertension, diabetes mellitus and Fabry disease as pathophysiological mechanisms and explored the therapeutic options related to these conditions including medications such as Canakinumab. Endothelial dysfunction has a key role in several different pathophysiological processes which can be targeted for therapeutic options. Ongoing research should be targeted at making the transition to clinical practice. Further research is also needed on understanding the amelioration of endothelial dysfunction with the use of cardiovascular medications.
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Mendelian Randomization Analysis Provides Insights into the Pathogenesis of Serum Levels of Branched-Chain Amino Acids in Cardiovascular Disease.
Metabolites2023 Mar;13(3):. doi: 403.
Jiang Wenxi, Lu Ke, Zhuang Zhenhuang, Wang Xue, Tang Xun, Huang Tao, Gao Pei, Wang Yuan, Du Jie,
Abstract
Several observational studies have indicated an association between high serum levels of branched-chain amino acids (BCAAs) and an increased risk of cardiovascular disease (CVD). To assess whether theses associations reflect causality, we carried out two-sample Mendelian randomization (MR). Single-nucleotide polymorphisms (SNPs) associated with BCAA were evaluated in 10 studies, including 24,925 participants. The association between SNPs and coronary artery disease (CAD) were assessed using summary estimates from the CARDIoGRAMplusC4D consortium. Further MR analysis of BCAAs and seven CVD outcomes was performed. The BCAA-raising gene functions were also analyzed. MR analyses revealed a risk-increasing causal relationship between serum BCAA concentrations and CAD (odds ratio 1.08; 95% confidence interval (CI) 1.02-1.14), which was partly mediated by blood pressure and type 2 diabetes. BCAA also demonstrated a causal relationship with ischemic CVD events induced by plaque rupture and thrombosis (false discovery rate
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Comparison of Characteristics and Outcomes of Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome in Children.
Medicina (Kaunas)2023 Mar;59(3):. doi: 626.
Klavina Lizete, Smane Liene, Kivite-Urtane Anda, Vasilevska Lauma, Davidsone Zane, Smitins Emils, Gardovska Dace, Lubaua Inguna, Roge Ieva, Pucuka Zanda, Meiere Anija, Pavare Jana,
Abstract
Since the first cases of multisystem inflammatory syndrome in children (MIS-C) in April 2020, the diagnostic challenge has been to recognize this syndrome and to differentiate it from other clinically similar pathologies such as Kawasaki disease (KD) and toxic shock syndrome (TSS). Our objective is to compare clinical signs, laboratory data and instrumental investigations between patients with MIS-C, KD and TSS. This retrospective observational study was conducted at the Children's Clinical University Hospital, Latvia (CCUH). We collected data from all pediatric patients
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