Adriana Georgescu | Institute of Cellular Biology and Pathology "Nicolae Simionescu" Romanian Academy (original) (raw)

Papers by Adriana Georgescu

Supplemental Material, suppl1 for Integrins α4β1 and αVβ3 are Reduced in Endothelial Progenitor C... more Supplemental Material, suppl1 for Integrins α4β1 and αVβ3 are Reduced in Endothelial Progenitor Cells from Diabetic Dyslipidemic Mice and May Represent New Targets for Therapy in Aortic Valve Disease by Alexandru Filippi, Alina Constantin, Nicoleta Alexandru, Geanina Voicu, Cristina Ana Constantinescu, Daniela Rebleanu, Madalina Fenyo, Dan Simionescu, Agneta Simionescu, Ileana Manduteanu and Adriana Georgescu in Cell Transplantation

Supplemental material, Answers_to_Reviewers_Rev2 for Diabetes-induced early molecular and functio... more Supplemental material, Answers_to_Reviewers_Rev2 for Diabetes-induced early molecular and functional changes in aortic heart valves in a murine model of atherosclerosis by Monica Madalina Tucureanu, Alexandru Filippi, Nicoleta Alexandru, Cristina Ana Constantinescu, Letitia Ciortan, Razvan Macarie, Mihaela Vadana, Geanina Voicu, Sabina Frunza, Dan Nistor, Agneta Simionescu, Dan Teodor Simionescu, Adriana Georgescu and Ileana Manduteanu in Diabetes & Vascular Disease Research

Cardiovascular Diabetology

Background Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiologic... more Background Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions by post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes and dyslipidemia. We aimed to identify new common miRNAs both in MVs and plasma that could be predictive biomarkers for diabetic dyslipidemia evolution. Methods For this purpose, plasma from 63 participants in the study (17 type 2 diabetic patients, 17 patients with type 2 diabetes and dyslipidemia, 14 patients with dyslipidemia alone and 15 clinically healthy persons without diabetes or dyslipidemia) was used for the analysis of circulating cytokines, MVs, miRNAs and MV-associated miRNAs. Results The results uncovered three miRNAs, miR-218, miR-132 and miR-143, whose expression was found to be significantly up-regulated in both circulating MVs and plasma from diabetic patients with dyslipidemia. These miRNAs showed significant correlations wit...

International Journal of Molecular Sciences

Glioblastoma (GB) is the most aggressive and recurrent form of brain cancer in adults. We hypothe... more Glioblastoma (GB) is the most aggressive and recurrent form of brain cancer in adults. We hypothesized that the identification of biomarkers such as certain microRNAs (miRNAs) and the circulating microvesicles (MVs) that transport them could be key to establishing GB progression, recurrence and therapeutic response. For this purpose, circulating MVs were isolated from the plasma of GB patients (before and after surgery) and of healthy subjects and characterized by flow cytometry. OpenArray profiling and the individual quantification of selected miRNAs in plasma and MVs was performed, followed by target genes’ prediction and in silico survival analysis. It was found that MVs’ parameters (number, EGFRvIII and EpCAM) decreased after the surgical resection of GB tumors, but the inter-patient variability was high. The expression of miR-106b-5p, miR-486-3p, miR-766-3p and miR-30d-5p in GB patients’ MVs was restored to control-like levels after surgery: miR-106b-5p, miR-486-3p and miR-766-...

Biomolecules

Both cardiovascular disease and cancer continue to be causes of morbidity and mortality all over ... more Both cardiovascular disease and cancer continue to be causes of morbidity and mortality all over the world. Preventing and treating heart disease in patients undergoing cancer treatment remain an important and ongoing challenge for improving the lives of cancer patients, but also for their survival. Despite ongoing efforts to improve patient survival, minimal advances have been made in the early detection of cardiovascular disease in patients suffering from cancer. Understanding the communication between cancer and cardiovascular disease can be based on a deeper knowledge of the molecular mechanisms that define the profile of the bilateral network and establish disease-specific biomarkers and therapeutic targets. The role of exosomes, microvesicles, and apoptotic bodies, together defined as extracellular vesicles (EVs), in cross talk between cardiovascular disease and cancer is in an incipient form of research. Here, we will discuss the preclinical evidence on the bilateral connecti...

Pharmaceutics, May 17, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Mechanisms of Vascular Defects in Diabetes Mellitus, 2017

Diabetes mellitus, a metabolic disorder characterized by high blood glucose, is one of the main r... more Diabetes mellitus, a metabolic disorder characterized by high blood glucose, is one of the main risk factors in the development of vascular complications affecting both large and small blood vessels. A major challenge is the discovery of new mediators and biomarkers for diabetes-related vascular complications. In this regard, accumulating evidence indicate that endothelial progenitor cells (EPCs), derived from the bone marrow and peripheral blood, are critical for the maintenance and regeneration of endothelial cells contributing to repair and restoration of vascular wall integrity. The studies reveal that the reduced number of circulating EPCs under diabetic conditions can predict cardiovascular outcomes, and EPC dysfunction could contribute to the pathogenesis of diabetes – associated vascular disease.

Frontiers in Pharmacology

Cardiac pathological hypertrophy is the major risk factor that usually progresses to heart failur... more Cardiac pathological hypertrophy is the major risk factor that usually progresses to heart failure. We hypothesized that extracellular vesicles (EVs), known to act as important mediators in regulating physiological and pathological functions, could have the potential to reduce the cardiac hypertrophy and the ensuing cardiovascular diseases. Herein, the effects of mesenchymal stem cell-derived extracellular vesicles (EV-MSCs) on cardiac hypertrophy were investigated. EVs were isolated from the secretome of human adipose tissue-derived stem cells (EV-ADSCs) or bone marrow-derived stem cells (EV-BMMSCs). Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were stimulated with AngII and TGF-β1, in absence or presence of EVs. The results showed that exposure of hiPSC-CMs to AngII and TGF-β1 generated in vitro model of hypertrophic cardiomyocytes characterized by increases in surface area, reactive oxygen species production, protein expression of cardiac-specific biomar...

Cardiovascular Research, 2016

Frontiers in Cell and Developmental Biology

Atherosclerosis is a progressive, chronic inflammatory disease of the large arteries caused by th... more Atherosclerosis is a progressive, chronic inflammatory disease of the large arteries caused by the constant accumulation of cholesterol, followed by endothelial dysfunction and vascular inflammation. We hypothesized that delivery of extracellular vesicles (EVs), recognized for their potential as therapeutic targets and tools, could restore vascular function in atherosclerosis. We explored by comparison the potential beneficial effects of EVs from subcutaneous adipose tissue stem cells (EVs (ADSCs)) or bone marrow mesenchymal stem cells (EVs (MSCs)) on the consequences of atherogenic diet on vascular health. Also, the influences of siRNA-targeting Smad2/3 (Smad2/3siRNA) on endothelial dysfunction and its key molecular players were analyzed. For this study, an animal model of atherosclerosis (HH) was transplanted with EVs (ADSCs) or EVs (MSCs) transfected or not with Smad2/3siRNA. For controls, healthy or HH animals were used. The results indicated that by comparison with the HH group...

Supplemental material, Supplementary_figure_1 for Diabetes-induced early molecular and functional... more Supplemental material, Supplementary_figure_1 for Diabetes-induced early molecular and functional changes in aortic heart valves in a murine model of atherosclerosis by Monica Madalina Tucureanu, Alexandru Filippi, Nicoleta Alexandru, Cristina Ana Constantinescu, Letitia Ciortan, Razvan Macarie, Mihaela Vadana, Geanina Voicu, Sabina Frunza, Dan Nistor, Agneta Simionescu, Dan Teodor Simionescu, Adriana Georgescu and Ileana Manduteanu in Diabetes & Vascular Disease Research

Thrombosis Research, 2015

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fib... more Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production.

Cellular Physiology and Biochemistry, 2011

Wharton's jelly (WJ) is a rich source of multiple-lineage differentiating cells, recently propose... more Wharton's jelly (WJ) is a rich source of multiple-lineage differentiating cells, recently proposed for cell replacement therapy. However, their ability to integrate into the cardiac tissue has not been elucidated, yet. We employed in vitro cardiac transplantation models to investigate the capacity of a novel population of human WJ-derived mesenchymal stem cells (nMSCs) to integrate into both living and ischemic cardiac tissue. NMSCs were characterized for the expression of stem/progenitor cell genes and proteins, as well as for multi-lineage differentiation potential. To assess their integration properties, nMSCs were cocultured with either living or ischemic embryonic murine ventricular slices. Immunohistochemical analyses were performed on cryosections of cocultured preparations to allow human cells tracking within the cocultures. Results showed that nMSCs shared MSC and endothelial colony-forming cell characteristics at gene, protein, and functional levels. NMSCs were markedly chemoattracted towards the ventricular slices, integrating robustly into the depth of both living and ischemic cardiac tissue. In conclusion, the functional ability of WJ-derived cells to populate the cardiac tissue could be validated in vitro. The transplantation models described could be further used to depict the mechanisms of WJ-derived cells integration into the cardiac tissue, contributing to optimization of reliable cell therapies for cardiac repair.

Reviews in Endocrine and Metabolic Disorders

Extracellular vesicles (EVs) are small anuclear vesicles, delimited by a lipid bilayer, released ... more Extracellular vesicles (EVs) are small anuclear vesicles, delimited by a lipid bilayer, released by almost all cell types, carrying functionally active biological molecules that can be transferred to the neighbouring or distant cells, inducing phenotypical and functional changes, relevant in various physio-pathological conditions. The microRNAs are the most significant active components transported by EVs, with crucial role in intercellular communication and significant effects on recipient cells. They may also server as novel valuable biomarkers for the diagnosis of metabolic disorders. Moreover, EVs are supposed to mediate type 2 diabetes mellitus (T2DM) risk and its progress. The T2DM development is preceded by prediabetes, a state that is associated with early forms of nephropathy and neuropathy, chronic kidney disease, diabetic retinopathy, and increased risk of macrovascular disease. Although the interest of scientists was focused not only on the pathogenesis of diabetes, but also on the early diagnosis, little is known about EVs-incorporated microRNA involvement in prediabetes state and its microvascular and macrovascular complications. Here, we survey the biogenesis, classification, content, biological functions and the most popular primary isolation methods of EVs, review the EVs—associated microRNA profiling connexion with early stages of diabetes and discuss the role of EVs containing specific microRNAs in prediabetes complications.

Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by poor su... more Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by poor survival rates and lack of effective therapies. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally through specific pairing with target messenger RNAs (mRNAs). Extracellular vesicles (EVs), a heterogeneous group of cell-derived vesicles, transport miRNAs, mRNAs and intracellular proteins, and have been shown to promote horizontal malignancy into adjacent tissue, as well as resistance to conventional therapies. Furthermore, GB-derived EVs have distinct miRNA contents and are able to penetrate the blood–brain barrier. Numerous studies have attempted to identify EV-associated miRNA biomarkers in serum/plasma and cerebrospinal fluid, but their collective findings fail to identify reliable biomarkers that can be applied in clinical settings. However, EVs carrying specific miRNAs or miRNA inhibitors have great potential as therapeutic nanotools in ...

Endothelial progenitor cells (EPCs) and circulating microparticles (MPs) have been proposed as ma... more Endothelial progenitor cells (EPCs) and circulating microparticles (MPs) have been proposed as markers of endothelial function. In turn, the protective role of irbesartan, an angiotensin receptor blocker, on the endothelium has been demonstrated in the recent years but the mechanism has not been yet fully elucidated. In this context, we investigated whether irbesartan can influence these two new biomarkers in patients with cardiovascular (CV) risk factors. We compared the levels of EPCs and MPs in patients with hypertension and dyslipidemia which received irbesartan with the levels in patients with the same CV risk factors but receiving other antihypertensive drugs and in healthy individuals. Using this methodology we showed the positive effect of angiotensin receptor blockade on the two proposed markers of endothelial function, reflecting both endothelial injury and repair, MPs and EPC respectively, in the same subjects with cardiovascular risk factors. Moreover, we found that pati...

INTRODUCTION Extracellular vesicles (EVs), including circulating microvesicles (MVs) or mi- cropa... more INTRODUCTION Extracellular vesicles (EVs), including circulating microvesicles (MVs) or mi- croparticles (MPs) and exosomes, derived from cells or platelets are present in the peripheral blood and are important elements involved in the activation of the coagulation system, transport of macromolecules and intercellular communication. In patients with vascular complications (including diabetes), the number of EVs is significantly increased during the acute phase of the disease. However, less is known about EVs release in the chronic state of diabetes. OBJECTIVES To analyse the profile of inflammatory cytokines and angiogenic factors in EVs in diabetic patients with ocular and vascular complications. PATIENTS AND METHODS The study included patients with diabetes and varying degrees of ocular complications including retinopathy (n = 48) and the control group (n = 13). EV-enriched and EV-depleted fractions were obtained from platelet-poor plasma by means of the centrifugation method (16 ...