Flavonoids are polyphenolic compounds found in a wide range of foods, including fruits, vegetables, tea plants, and other natural products. They have been mainly classified as flavanols, flavonols, flavones, isoflavones, flavanones, and flavanonols. In this comprehensive review, we will discuss preclinical pieces of evidence on the potential of flavonoids for the prevention/treatment of myocardial ischemia-reperfusion (IR) injury.
Key findings
In-vitro and in-vivo studies have shown that flavonoids play an important role in preventing ischemic heart disease (IHD). They possess strong anti-oxidant, anti-inflammatory, anti-bacterial, anti-thrombotic, anti-apoptotic, and anti-carcinogenic activities. In addition, at a molecular level, flavonoids also modulate various pathways like MAPK, NFκB etc. to confer beneficial effects.
Summary
The current review of flavonoids in myocardial ischemia-reperfusion injury furnishes updated information that could drive future research. The in-vitro and in-vivo experiments have demonstrated various favourable pharmacological properties of flavonoids. This review provides valuable information to conduct clinical studies, validating the safety aspects of flavonoids in the clinical domain.
{"title":"Molecular mechanisms of flavonoids in myocardial ischemia reperfusion injury: Evidence from in-vitro and in-vivo studies","authors":"Jatin Sharma , Poorva Bhargava , Prashant Mishra , Jagriti Bhatia , Dharamvir Singh Arya","doi":"10.1016/j.vph.2024.107378","DOIUrl":"10.1016/j.vph.2024.107378","url":null,"abstract":"<div><h3>Objectives</h3><p>Flavonoids are polyphenolic compounds found in a wide range of foods, including fruits, vegetables, tea plants, and other natural products. They have been mainly classified as flavanols, flavonols, flavones, isoflavones, flavanones, and flavanonols. In this comprehensive review, we will discuss preclinical pieces of evidence on the potential of flavonoids for the prevention/treatment of myocardial ischemia-reperfusion (IR) injury.</p></div><div><h3>Key findings</h3><p><em>In-vitro</em> and <em>in-vivo</em> studies have shown that flavonoids play an important role in preventing ischemic heart disease (IHD). They possess strong anti-oxidant, anti-inflammatory, anti-bacterial, anti-thrombotic, anti-apoptotic, and anti-carcinogenic activities. In addition, at a molecular level, flavonoids also modulate various pathways like MAPK, NFκB <em>etc.</em> to confer beneficial effects.</p></div><div><h3>Summary</h3><p>The current review of flavonoids in myocardial ischemia-reperfusion injury furnishes updated information that could drive future research. The <em>in-vitro</em> and <em>in-vivo</em> experiments have demonstrated various favourable pharmacological properties of flavonoids. This review provides valuable information to conduct clinical studies, validating the safety aspects of flavonoids in the clinical domain.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1016/j.vph.2024.107377
Martin Malý , Ondřej Kučerka , Kamila Bechyňská , Karolína Kočí , Václav Mandys , Jana Hajšlová , Vít Kosek
Background
Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events.
Aim
We studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque.
Methods
This study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques.
Results
The lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification.
Conclusions
Plasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.
{"title":"Plasma lipidome differences in patients with and without significant carotid plaque","authors":"Martin Malý , Ondřej Kučerka , Kamila Bechyňská , Karolína Kočí , Václav Mandys , Jana Hajšlová , Vít Kosek","doi":"10.1016/j.vph.2024.107377","DOIUrl":"10.1016/j.vph.2024.107377","url":null,"abstract":"<div><h3>Background</h3><p>Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events.</p></div><div><h3>Aim</h3><p>We studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque.</p></div><div><h3>Methods</h3><p>This study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques.</p></div><div><h3>Results</h3><p>The lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification.</p></div><div><h3>Conclusions</h3><p>Plasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1016/j.vph.2024.107379
Beate Christiane Schlueter, K. Quanz, Julia Baldauf, Aleksandar Petrovic, C. Ruppert, Andreas Guenther, H. Gall, Khodr Tello, F. Grimminger, H. Ghofrani, Norbert Weissmann, Werner Seeger, Ralph T Schermuly, Astrid Weiss
{"title":"The diverging roles of insulin-like growth factor binding proteins in pulmonary arterial hypertension","authors":"Beate Christiane Schlueter, K. Quanz, Julia Baldauf, Aleksandar Petrovic, C. Ruppert, Andreas Guenther, H. Gall, Khodr Tello, F. Grimminger, H. Ghofrani, Norbert Weissmann, Werner Seeger, Ralph T Schermuly, Astrid Weiss","doi":"10.1016/j.vph.2024.107379","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107379","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141044268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.1016/j.vph.2024.107376
Sophia Kalanski , Stuti Pradhan , Andy Hon , Yuxuan Xia , Nora Safvati , Juan Carlos Rivera , Mimi Lu , Linda L. Demer , Yin Tintut
Cardiovascular disease and osteoporosis, major causes of morbidity and mortality, are associated with hyperlipidemia. Recent studies show that empagliflozin (EMPA), an inhibitor of sodium-glucose cotransporter-2 (SGLT2), improves cardiovascular health. In preclinical animal studies, EMPA mitigates vascular calcification in the males but its effects in the females are not known. Thus, we used female mice to test the effects of EMPA on calcification in the artery wall, cardiac function, and skeletal bone. By serial in vivo microCT imaging, we followed the progression of aortic calcification and bone mineral density in young and older female Apoe−/− mice fed a high-fat diet with or without EMPA. The two different age groups were used to compare early vs. advanced stages of aortic calcification. Results show that EMPA treatment increased urine glucose levels. Aortic calcium content increased in both the controls and the EMPA-treated mice, and EMPA did not affect progression of aortic calcium content in both young and older mice. However, 3-D segmentation analysis of aortic calcium deposits on microCT images revealed that EMPA-treated mice had significantly less surface area and volume of calcified deposits as well as fewer numbers of deposits than the control mice. To test for direct effects on vascular cell calcification, we treated murine aortic smooth muscle cells with EMPA, and results showed a slight inhibition of alkaline phosphatase activity and inflammatory matrix calcification. As for skeletal bone, EMPA-treated mice had significantly lower BMD than the controls in both the lumbar vertebrae and femoral bones in both young and older mice. The findings suggest that, in hyperlipidemic female mice, unlike males, SGLT2 inhibition with empagliflozin does not mitigate progression of aortic calcification and may even lower skeletal bone density.
{"title":"Effects of Empagliflozin on Vascular and Skeletal Mineralization in Hyperlipidemic Mice","authors":"Sophia Kalanski , Stuti Pradhan , Andy Hon , Yuxuan Xia , Nora Safvati , Juan Carlos Rivera , Mimi Lu , Linda L. Demer , Yin Tintut","doi":"10.1016/j.vph.2024.107376","DOIUrl":"10.1016/j.vph.2024.107376","url":null,"abstract":"<div><p>Cardiovascular disease and osteoporosis, major causes of morbidity and mortality, are associated with hyperlipidemia. Recent studies show that empagliflozin (EMPA), an inhibitor of sodium-glucose cotransporter-2 (SGLT2), improves cardiovascular health. In preclinical animal studies, EMPA mitigates vascular calcification in the males but its effects in the females are not known. Thus, we used female mice to test the effects of EMPA on calcification in the artery wall, cardiac function, and skeletal bone. By serial in vivo microCT imaging, we followed the progression of aortic calcification and bone mineral density in young and older female <em>Apoe</em><sup><em>−/−</em></sup> mice fed a high-fat diet with or without EMPA. The two different age groups were used to compare early vs. advanced stages of aortic calcification. Results show that EMPA treatment increased urine glucose levels. Aortic calcium content increased in both the controls and the EMPA-treated mice, and EMPA did not affect progression of aortic calcium content in both young and older mice. However, 3-D segmentation analysis of aortic calcium deposits on microCT images revealed that EMPA-treated mice had significantly less surface area and volume of calcified deposits as well as fewer numbers of deposits than the control mice. To test for direct effects on vascular cell calcification, we treated murine aortic smooth muscle cells with EMPA, and results showed a slight inhibition of alkaline phosphatase activity and inflammatory matrix calcification. As for skeletal bone, EMPA-treated mice had significantly lower BMD than the controls in both the lumbar vertebrae and femoral bones in both young and older mice. The findings suggest that, in hyperlipidemic female mice, unlike males, SGLT2 inhibition with empagliflozin does not mitigate progression of aortic calcification and may even lower skeletal bone density.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.1016/j.vph.2024.107375
Luca Visconti , Alessandro Celi , Laura Carrozzi , Camilla Tinelli , Laura Crocetti , Francesco Daviddi , Raffaele De Caterina , Rosalinda Madonna , Roberta Pancani
Anticoagulation is the first-line approach in the prevention and treatment of pulmonary embolism. In some instances, however, anticoagulation fails, or cannot be administered due to a high risk of bleeding. Inferior vena cava filters are metal alloy devices that mechanically trap emboli from the deep leg veins halting their transit to the pulmonary circulation, thus providing a mechanical alternative to anticoagulation in such conditions. The Greenfield filter was developed in 1973 and was later perfected to a model that could be inserted percutaneously. Since then, this model has been the reference standard. The current class I indication for this device includes absolute contraindication to anticoagulants in the presence of acute thromboembolism and recurrent thromboembolism despite adequate therapy. Additional indications have been more recently proposed, due to the development of removable filters and of progressively less invasive techniques.
Although the use of inferior vena cava filters has solid theoretical advantages, clinical efficacy and adverse event profile are still unclear. This review analyzes the most important studies related to such devices, open issues, and current guideline recommendations.
抗凝是预防和治疗肺栓塞的一线方法。但在某些情况下,抗凝治疗会失败,或因出血风险高而无法实施。下腔静脉过滤器是一种金属合金装置,可机械性地捕获来自腿部深静脉的栓子,阻止其进入肺循环,从而在这种情况下提供一种抗凝治疗的机械替代方法。格林菲尔德过滤器开发于 1973 年,后来改进为可经皮插入的型号。从那时起,这种型号一直是参考标准。该设备目前的 I 类适应症包括急性血栓栓塞和接受适当治疗后仍复发血栓栓塞的绝对抗凝禁忌症。虽然下腔静脉滤器的使用具有坚实的理论基础,但其临床疗效和不良反应仍不明确。本综述分析了与此类设备相关的最重要研究、未决问题以及当前的指南建议。
{"title":"Inferior vena cava filters: Concept review and summary of current guidelines","authors":"Luca Visconti , Alessandro Celi , Laura Carrozzi , Camilla Tinelli , Laura Crocetti , Francesco Daviddi , Raffaele De Caterina , Rosalinda Madonna , Roberta Pancani","doi":"10.1016/j.vph.2024.107375","DOIUrl":"10.1016/j.vph.2024.107375","url":null,"abstract":"<div><p>Anticoagulation is the first-line approach in the prevention and treatment of pulmonary embolism. In some instances, however, anticoagulation fails, or cannot be administered due to a high risk of bleeding. Inferior vena cava filters are metal alloy devices that mechanically trap emboli from the deep leg veins halting their transit to the pulmonary circulation, thus providing a mechanical alternative to anticoagulation in such conditions. The Greenfield filter was developed in 1973 and was later perfected to a model that could be inserted percutaneously. Since then, this model has been the reference standard. The current class I indication for this device includes absolute contraindication to anticoagulants in the presence of acute thromboembolism and recurrent thromboembolism despite adequate therapy. Additional indications have been more recently proposed, due to the development of removable filters and of progressively less invasive techniques.</p><p>Although the use of inferior vena cava filters has solid theoretical advantages, clinical efficacy and adverse event profile are still unclear. This review analyzes the most important studies related to such devices, open issues, and current guideline recommendations.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1537189124001010/pdfft?md5=5af3f298e6e417f91a52189892af40fc&pid=1-s2.0-S1537189124001010-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1016/j.vph.2024.107374
Michele D'Alto , Roberto Badagliacca , Edoardo Airò , Pietro Ameri , Paola Argiento , Andrea Garascia , Carlo Mario Lombardi , Massimiliano Mulè , Claudia Raineri , Laura Scelsi , Carmine Dario Vizza , Stefano Ghio
A comprehensive evaluation of risk, using multiple indices, is necessary to provide reliable prognostic information and guide therapy in pulmonary arterial hypertension (PAH). The current ESC/ERS guidelines suggest using a three-strata model for incident (newly diagnosed) patients and a four-strata model for prevalent patients with PAH.
The four-strata model serves as a fundamental risk-stratification tool and relies on a minimal dataset of indicators that must be considered during follow-up. Nevertheless, there are still areas of vagueness and ambiguity when classifying and managing patients in the intermediate-risk category. For these patients, considerations should include right heart imaging, hemodynamics, as well as individual factors such as age, sex, genetic profile, disease type, comorbidities, and kidney function.
The aim of this report is to present case studies, with a specific focus on patients ultimately classified as intermediate risk. We aim to emphasize the challenges and complexities encountered in the realms of diagnosis, classification, and treatment for these particular patients.
{"title":"Gaps in evidence in the management of patients with intermediate-risk pulmonary arterial hypertension: Considerations following the ESC/ERS 2022 guidelines","authors":"Michele D'Alto , Roberto Badagliacca , Edoardo Airò , Pietro Ameri , Paola Argiento , Andrea Garascia , Carlo Mario Lombardi , Massimiliano Mulè , Claudia Raineri , Laura Scelsi , Carmine Dario Vizza , Stefano Ghio","doi":"10.1016/j.vph.2024.107374","DOIUrl":"10.1016/j.vph.2024.107374","url":null,"abstract":"<div><p>A comprehensive evaluation of risk, using multiple indices, is necessary to provide reliable prognostic information and guide therapy in pulmonary arterial hypertension (PAH). The current ESC/ERS guidelines suggest using a three-strata model for incident (newly diagnosed) patients and a four-strata model for prevalent patients with PAH.</p><p>The four-strata model serves as a fundamental risk-stratification tool and relies on a minimal dataset of indicators that must be considered during follow-up. Nevertheless, there are still areas of vagueness and ambiguity when classifying and managing patients in the intermediate-risk category. For these patients, considerations should include right heart imaging, hemodynamics, as well as individual factors such as age, sex, genetic profile, disease type, comorbidities, and kidney function.</p><p>The aim of this report is to present case studies, with a specific focus on patients ultimately classified as intermediate risk. We aim to emphasize the challenges and complexities encountered in the realms of diagnosis, classification, and treatment for these particular patients.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1016/j.vph.2024.107371
Daniel Morales-Cano , Bianca Barreira , María Callejo , Miguel A. Olivencia , Antonio Ferruelo , Javier Milara , José Ángel Lorente , Laura Moreno , Ángel Cogolludo , Francisco Perez-Vizcaino
An effective pulmonary hypertension (PH) treatment should combine antiproliferative and vasodilator effects. We characterized a wide-range of drugs comparing their anti-proliferative vs vasodilator effects in human and rat pulmonary artery smooth muscle cells (PASMC). Key findings: 1) Approved PH drugs (PDE5 inhibitors, sGC stimulators and PGI2 agonists) are preferential vasodilators. 2) cGMP stimulators were more effective in cells derived from hypertensive rats. 3) Nifedipine acted equally as vasodilator and antiproliferative. 4) quercetin and imatinib were potent dual vasodilator/antiproliferative drugs. 5) Tacrolimus and levosimendan lacked antiproliferative effects. 6) Forskolin, pinacidil and hydroxyfasudil were more effective as antiproliferative in human cells.
{"title":"Comparative analysis of antiproliferative and vasodilator effects of drugs for pulmonary hypertension: Extensive in vitro study in rats and human","authors":"Daniel Morales-Cano , Bianca Barreira , María Callejo , Miguel A. Olivencia , Antonio Ferruelo , Javier Milara , José Ángel Lorente , Laura Moreno , Ángel Cogolludo , Francisco Perez-Vizcaino","doi":"10.1016/j.vph.2024.107371","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107371","url":null,"abstract":"<div><p>An effective pulmonary hypertension (PH) treatment should combine antiproliferative and vasodilator effects. We characterized a wide-range of drugs comparing their anti-proliferative vs vasodilator effects in human and rat pulmonary artery smooth muscle cells (PASMC). Key findings: 1) Approved PH drugs (PDE5 inhibitors, sGC stimulators and PGI<sub>2</sub> agonists) are preferential vasodilators. 2) cGMP stimulators were more effective in cells derived from hypertensive rats. 3) Nifedipine acted equally as vasodilator and antiproliferative. 4) quercetin and imatinib were potent dual vasodilator/antiproliferative drugs. 5) Tacrolimus and levosimendan lacked antiproliferative effects. 6) Forskolin, pinacidil and hydroxyfasudil were more effective as antiproliferative in human cells.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140551166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-06DOI: 10.1016/j.vph.2024.107372
Priscila R. Nunes , Pedro F. Oliveira , Irene Rebelo , Valeria C. Sandrim , Marco G. Alves
Oxidative stress and mitochondrial dysfunction are important elements for the pathophysiology of preeclampsia (PE), a multisystemic hypertensive syndrome of pregnancy, characterized by endothelial dysfunction and responsible for a large part of maternal and fetal morbidity and mortality worldwide. Researchers have dedicated their efforts to unraveling the intricate ways in which certain molecules influence both energy metabolism and oxidative stress. Exploring established methodologies from existing literature, shows that these investigations predominantly focus on the placenta, identified as a pivotal source that drives the changes observed in the disease. In this review, we discuss the role of oxidative stress in pathophysiology of PE, as well as metabolic/endothelial dysfunction. We further discuss the use of seahorse analyzers to study real-time bioenergetics of endothelial cells. Although the benefits are clear, few studies have presented results using this method to assess mitochondrial metabolism in these cells. We performed a search on MEDLINE/PubMed using the terms “Seahorse assay and endothelial dysfunction in HUVEC” as well as “Seahorse assay and preeclampsia”. From our research, we selected 16 original peer-review papers for discussion. Notably, the first search retrieved studies involving Human Umbilical Vein Endothelial Cells (HUVECs) but none investigating bioenergetics in PE while the second search retrieved studies exploring the technique in PE but none of the studies used HUVECs. Additional studies are required to investigate real-time mitochondrial bioenergetics in PE. Clearly, there is a need for more complete studies to examine the nuances of mitochondrial bioenergetics, focusing on the contributions of HUVECs in the context of PE.
氧化应激和线粒体功能障碍是子痫前期(PE)病理生理学的重要因素,子痫前期是一种多系统妊娠高血压综合征,以血管内皮功能障碍为特征,是全球大部分孕产妇和胎儿发病和死亡的原因。研究人员致力于揭示某些分子影响能量代谢和氧化应激的复杂方式。通过对现有文献中的既定方法进行探讨,我们发现这些研究主要集中在胎盘上,而胎盘被认为是驱动疾病发生变化的关键源头。在这篇综述中,我们讨论了氧化应激在 PE 病理生理学中的作用,以及代谢/内皮功能障碍。我们进一步讨论了使用海马分析仪研究内皮细胞的实时生物能。虽然这种方法的优点显而易见,但很少有研究利用这种方法来评估这些细胞的线粒体代谢。我们使用 "海马测定和 HUVEC 内皮功能障碍 "以及 "海马测定和子痫前期 "这两个词在 MEDLINE/PubMed 上进行了搜索。通过研究,我们选择了 16 篇同行评审的原创论文进行讨论。值得注意的是,第一次搜索检索到的研究涉及人脐静脉内皮细胞(HUVECs),但没有研究 PE 中的生物能;第二次搜索检索到的研究探讨了 PE 中的生物能技术,但没有研究使用 HUVECs。要研究 PE 中线粒体的实时生物能,还需要进行更多的研究。显然,有必要进行更全面的研究,以检查线粒体生物能的细微差别,重点关注 HUVECs 在 PE 中的贡献。
{"title":"Relevance of real-time analyzers to determine mitochondrial quality in endothelial cells and oxidative stress in preeclampsia","authors":"Priscila R. Nunes , Pedro F. Oliveira , Irene Rebelo , Valeria C. Sandrim , Marco G. Alves","doi":"10.1016/j.vph.2024.107372","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107372","url":null,"abstract":"<div><p>Oxidative stress and mitochondrial dysfunction are important elements for the pathophysiology of preeclampsia (PE), a multisystemic hypertensive syndrome of pregnancy, characterized by endothelial dysfunction and responsible for a large part of maternal and fetal morbidity and mortality worldwide. Researchers have dedicated their efforts to unraveling the intricate ways in which certain molecules influence both energy metabolism and oxidative stress. <strong>Exploring</strong> established methodologies from existing literature, <strong>shows that</strong> these investigations predominantly focus on the placenta, identified as a pivotal source that <strong>drives</strong> the changes observed in the disease. In this review, we discuss the role of oxidative stress in pathophysiology of PE, as well as metabolic/endothelial dysfunction. We further discuss the use of seahorse analyzers to study real-time bioenergetics of endothelial cells. Although the benefits are clear, few studies have presented results using this method to assess mitochondrial metabolism in these cells. We performed a search on MEDLINE/PubMed using the terms “Seahorse assay and endothelial dysfunction in HUVEC” as well as “Seahorse assay and preeclampsia”. From our research, we selected 16 original peer-review papers for discussion. Notably, the first search retrieved studies involving <strong>Human Umbilical Vein Endothelial Cells</strong> (HUVECs) but none investigating bioenergetics in PE while the second search retrieved studies exploring the technique in PE but none of the studies used HUVECs. Additional studies are required to investigate real-time mitochondrial bioenergetics in PE. Clearly, there is a need for more complete studies to examine the nuances of mitochondrial bioenergetics, focusing on the contributions of HUVECs in the context of PE.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1537189124000971/pdfft?md5=070d4d7d762c8f7bd7b701296ed602b8&pid=1-s2.0-S1537189124000971-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1016/j.vph.2024.107370
Raffaele De Caterina, Peter Libby
{"title":"Coronary artery disease and myocardial ischemic syndromes 2023 Proceedings of an International Expert Meeting Pisa, Italy 16-17 June 2023","authors":"Raffaele De Caterina, Peter Libby","doi":"10.1016/j.vph.2024.107370","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107370","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-29DOI: 10.1016/j.vph.2024.107369
Dinesh Yadav , Jeremy A. Conner , Yimin Wang , Thomas L. Saunders , Eroboghene E. Ubogu
Mouse models are invaluable to understanding fundamental mechanisms in vascular biology during development, in health and different disease states. Several constitutive or inducible models that selectively knockout or knock in genes in vascular endothelial cells exist; however, functional and phenotypic differences exist between microvascular and macrovascular endothelial cells in different organs. In order to study microvascular endothelial cell-specific biological processes, we developed a Tamoxifen-inducible von Willebrand Factor (vWF) Cre recombinase mouse in the SJL background. The transgene consists of the human vWF promoter with the microvascular endothelial cell-selective 734 base pair sequence to drive Cre recombinase fused to a mutant estrogen ligand-binding domain [ERT2] that requires Tamoxifen for activity (CreERT2) followed by a polyadenylation (polyA) signal. We initially observed Tamoxifen-inducible restricted bone marrow megakaryocyte and sciatic nerve microvascular endothelial cell Cre recombinase expression in offspring of a mixed strain hemizygous C57BL/6-SJL founder mouse bred with mT/mG mice, with >90% bone marrow megakaryocyte expression efficiency. Founder mouse offspring were backcrossed to the SJL background by speed congenics, and intercrossed for >10 generations to develop hemizygous Tamoxifen-inducible vWF Cre recombinase (vWF-iCre/+) SJL mice with stable transgene insertion in chromosome 1. Microvascular endothelial cell-specific Cre recombinase expression occurred in the sciatic nerves, brains, spleens, kidneys and gastrocnemius muscles of adult vWF-iCre/+ SJL mice bred with Ai14 mice, with retained low level bone marrow and splenic megakaryocyte expression. This novel mouse strain would support hypothesis-driven mechanistic studies to decipher the role(s) of specific genes transcribed by microvascular endothelial cells during development, as well as in physiologic and pathophysiologic states in an organ- and time-dependent manner.
{"title":"A novel inducible von Willebrand Factor Cre recombinase mouse strain to study microvascular endothelial cell-specific biological processes in vivo","authors":"Dinesh Yadav , Jeremy A. Conner , Yimin Wang , Thomas L. Saunders , Eroboghene E. Ubogu","doi":"10.1016/j.vph.2024.107369","DOIUrl":"10.1016/j.vph.2024.107369","url":null,"abstract":"<div><p>Mouse models are invaluable to understanding fundamental mechanisms in vascular biology during development, in health and different disease states. Several constitutive or inducible models that selectively knockout or knock in genes in vascular endothelial cells exist; however, functional and phenotypic differences exist between microvascular and macrovascular endothelial cells in different organs. In order to study microvascular endothelial cell-specific biological processes, we developed a Tamoxifen-inducible von Willebrand Factor (vWF) Cre recombinase mouse in the SJL background. The transgene consists of the human vWF promoter with the microvascular endothelial cell-selective 734 base pair sequence to drive Cre recombinase fused to a mutant estrogen ligand-binding domain [ERT2] that requires Tamoxifen for activity (CreERT2) followed by a polyadenylation (polyA) signal. We initially observed Tamoxifen-inducible restricted bone marrow megakaryocyte and sciatic nerve microvascular endothelial cell Cre recombinase expression in offspring of a mixed strain hemizygous C57BL/6-SJL founder mouse bred with mT/mG mice, with >90% bone marrow megakaryocyte expression efficiency. Founder mouse offspring were backcrossed to the SJL background by speed congenics, and intercrossed for >10 generations to develop hemizygous Tamoxifen-inducible vWF Cre recombinase (vWF-iCre/+) SJL mice with stable transgene insertion in chromosome 1. Microvascular endothelial cell-specific Cre recombinase expression occurred in the sciatic nerves, brains, spleens, kidneys and gastrocnemius muscles of adult vWF-iCre/+ SJL mice bred with Ai14 mice, with retained low level bone marrow and splenic megakaryocyte expression. This novel mouse strain would support hypothesis-driven mechanistic studies to decipher the role(s) of specific genes transcribed by microvascular endothelial cells during development, as well as in physiologic and pathophysiologic states in an organ- and time-dependent manner.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}