scholarly journals Effects of MicroRNAs in Valvular Heart Diseases: From Molecular Pathways to Clinical Effects and Therapeutical Strategies

2021 ◽  
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Expression Vectors ◽  
Clinical Effects ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases ◽  
Micro Rnas

Micro-RNAs have been recently investigated in preclinical and clinical research as regulators of valvulopathies pathogenesis, diagnostic biomarkers and therapeutical targets. Evidences from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse, aortic leaflet fusion and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes or different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address mi-RNAs over or under-representation. In this review we discuss the fundamental intracellular homeostatic and cardiogenetic pathways regulated by mi-RNAs leading to defects in mitral and aortic valves, congenital heart diseases and the possible therapeutical strategies targeting them. Mi-RNAs inhibitors comprise antisense oligonucleotides and sponge vectors while mi-RNA mimics, mi-RNA expression vectors and small molecules are possible practical strategies to increase their activity. Advantages and technical limitations, including instability and complex pharmacokinetics are also presented. Novel strategies, such as nanoparticles and liposomes, are conclusively described to improve knowledge on these molecules delivery and establish future personalized treatment directions.

scholarly journals MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

2021 ◽  
Vol 22 (22) ◽  
pp. 12132
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Osteoblastic Differentiation ◽  
New Drugs ◽  
Expression Vectors ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases

miRNAs have recently attracted investigators’ interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

scholarly journals MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

2021 ◽  
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Osteoblastic Differentiation ◽  
New Drugs ◽  
Expression Vectors ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

scholarly journals Straight back syndrome as a clue to diagnosing asymptomatic congenital valvular heart disease and limiting the risk of weightlifting

2021 ◽  
Vol 121 (2) ◽  
pp. 135-140
Author(s):  
William A. Schiavone
Keyword(s):  
Mitral Valve ◽  
Heart Diseases ◽  
Severe Aortic Stenosis ◽  
Aortic Disease ◽  
Chordae Tendineae ◽  
Blood Pressure Elevation ◽  
The Public ◽  
Valvular Heart Diseases ◽  
Patients At Risk ◽  
The Common

Abstract Although both are initially asymptomatic, mitral valve prolapse/myxomatous mitral valve disease (MVP/MMVD) and bicuspid aortic valve (BAV), with its associated aortic disease, are currently the two most common congenital valvular heart diseases. Severe mitral regurgitation due to rupture of chordae tendineae (CTR) prompts surgery for MVP/MMVD. Surgery for BAV is performed for severe aortic stenosis and/or regurgitation, often with management of root and/or ascending aortic enlargement. There may be an association between straight back syndrome (SBS) and MVP/MMVD, which may be a key to earlier diagnosis. Other associations link weightlifting with ascending aortic enlargement and with CTR, where the common theme is blood pressure elevation. As the number of people with fitness center memberships continues to increase, this potentially exposes more undiagnosed individuals with MVP/MMVD or BAV to risk from weightlifting. Challenges include making the public aware of this risk and preparing the osteopathic physician to recognize patients at risk through a structured history-taking and targeted cardiovascular examination.

CORONARY ARTERY LESIONS IN PATIENTS OVER 50 YEAR OLD WITH VALVULAR HEART DISEASES INDICATED FOR VALVE SURGERY

2016 ◽  
pp. 20-24
Author(s):  
Bang Giap Vo ◽  
Anh Binh Ho ◽  
Van Minh Huynh
Keyword(s):  
Coronary Artery ◽  
Mitral Valve ◽  
Heart Valve ◽  
Right Coronary Artery ◽  
Heart Diseases ◽  
Heart Valve Diseases ◽  
Coronary Artery Lesions ◽  
Circumflex Coronary Artery ◽  
Valvular Heart Diseases ◽  
Valve Diseases

Objectives: To investigate the features of coronary artery lesions in patients over 50 with heart valve diseases and to find out the relationship between the levels of coronary artery lesions and heart valve diseases. Results: In patients over 50 year old with heart valve diseases, the rate of significant coronary artery lesions is 55.5%. In which, significant lesions in the group of both mitral and aorta valve diseases is 44.19%, only mitral valve diseases is of 70%, only aortic valve diseases is of 51.85%. There is a relationship between the severity of mitral valve diseases and right coronary artery lesions (OR 3.74: 1.64 to 8.5, p = 0.0017) and circumflex coronary artery lesions (OR 2.59: 1.16 to 5.75, p = 0.0192). The severity of heart valve lesions in significant coronary artery lesions group is higher than insignificant coronary artery lesions group or normal group. Conclusion: Coronary artery lesions is common in patients > 50 years old with heart valve diseases, there is a relationship between the severity of mitral valve diseases and and right coronary artery lesions and circumflex coronary artery lesions. Key words: coronary artery lesions, mitral valvediseases

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

scholarly journals Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3692-3700 ◽  
Author(s):  
Hui-Ping Gu ◽  
Sen Lin ◽  
Ming Xu ◽  
Hai-Yi Yu ◽  
Xiao-Jun Du ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Gene Promoter ◽  
Binding Motif ◽  
Endogenous Expression ◽  
G Quadruplex

Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.

scholarly journals Study of the Effects of Homeopathic Medicine Carcinosinum on Mammary Adenocarcinoma (4T1 cells) in vitro.

2021 ◽  
Vol 17 (2) ◽  
pp. 22-23
Author(s):  
Leoni Villano Bonamin ◽  
Thaís Cristina Silva ◽  
William Alves Santos ◽  
Sandra AG Pinto ◽  
Vanessa Xavier ◽  
...  
Keyword(s):  
Pure Water ◽  
Alcoholic Solution ◽  
Mammary Adenocarcinoma ◽  
Clinical Effects ◽  
Apoptosis Index ◽  
Her 2 ◽  
4T1 Cells ◽  
One Way Anova

Background: There are few published researches about the exclusive use of Carsinosinum in several potencies to treat cancer. The name Carcinosinum refers to any homeopathic preparation of epithelial cancerous tissues and is especially indicated when there are any hereditary and familial antecedents of cancer, tuberculosis, diabetes, pernicious anemia or a combination of two or more of these diseases. Homeopathic complexes which include Conium Maculatum, Sabal Serrulata, Thuja Occidentalis and Carcinosinum can reduce in 23% the incidence of prostate cancer in vivo and in 38% the tumor volume, compared to untreated groups. Another in vivo study revealed reduction of symptoms and increase of survival time in mice bearing Ehrlich ascitic carcinoma, after treatment with Carcinosinum 200cH. In vitro, Carcinosinum 200cH can increase the expression of the pro-apoptotic gene p53. However, mice treated with Carcinosinum 6cH had the highest percentage and diversity of symptoms compared to other treatments, which demonstrate the importance of homeopathic potency in pro or anti-carcinogenic action. Considering that the literature on this subject is still rare and focused on genotypic and clinical effects, the present study was proposed, with the aim of identifying the possible phenotypic changes, including viability, HER-2 expression and metastatic skills, using 4T1 cells in vitro as a model, after treatment with Carcinosinum in different homeopathic working dilutions (12cH; 30cH; 200cH), prepared mechanically (Denise Machine, Autic®) in our laboratory using sterile pure water, from a commercial matrix (HN Cristiano, São Paulo, Brazil) stocked in 70% hydro-alcoholic solution. The final dilutions were inserted in the culture medium in a volume equal to 10%, at the time of cell seeding. The same succussioned vehicle used to prepare the medicines (70% hydro-alcoholic solution), from the same batch and diluted 1:100 in sterile pure water, was used as control. All treated cells were cultivated in bottles of 25ml with cell density of 5 x 105 cells / ml and, after 24 hours of treatment, they were analyzed for the apoptosis index using the Annexin V kit and measured by the Countess® system. The morphology of the 4T1 cells was monitored by staining fixed cell smears with hematoxylin-eosin method. The samples were evaluated in quadruplicate and the data were analyzed by one-way ANOVA. The results obtained up to now show that the treatment with Carcinosinum 12cH produced a different pattern of cell death compared to the other treatments, with significant reduction in apoptosis index (one-way ANOVA, p=0.01) and clear hydropic degeneration phenotypic pattern. The analysis of HER-2 expression and metastatic skill will be the next step of this research.

scholarly journals Advanced Technologies to Target Cardiac Cell Fate Plasticity for Heart Regeneration

2021 ◽  
Vol 22 (17) ◽  
pp. 9517
Author(s):  
Gianluca Testa ◽  
Giorgia Di Benedetto ◽  
Fabiana Passaro
Keyword(s):  
Cell Fate ◽  
Disease Modeling ◽  
Heart Diseases ◽  
Cellular Reprogramming ◽  
Cardiac Cell ◽  
New Paradigm ◽  
Cardiovascular Research ◽  
Injured Myocardium

The adult human heart can only adapt to heart diseases by starting a myocardial remodeling process to compensate for the loss of functional cardiomyocytes, which ultimately develop into heart failure. In recent decades, the evolution of new strategies to regenerate the injured myocardium based on cellular reprogramming represents a revolutionary new paradigm for cardiac repair by targeting some key signaling molecules governing cardiac cell fate plasticity. While the indirect reprogramming routes require an in vitro engineered 3D tissue to be transplanted in vivo, the direct cardiac reprogramming would allow the administration of reprogramming factors directly in situ, thus holding great potential as in vivo treatment for clinical applications. In this framework, cellular reprogramming in partnership with nanotechnologies and bioengineering will offer new perspectives in the field of cardiovascular research for disease modeling, drug screening, and tissue engineering applications. In this review, we will summarize the recent progress in developing innovative therapeutic strategies based on manipulating cardiac cell fate plasticity in combination with bioengineering and nanotechnology-based approaches for targeting the failing heart.

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