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exosome and heart failure

Lucian Beer, Michael Mildner, Mariann Gyöngyösi, Hendrik Jan Ankersmit
For almost two decades, cell-based therapies have been tested in modern regenerative medicine to either replace or regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. These factors are called the cell secretome and include a variety of proteins, lipids, microRNAs, and extracellular vesicles, such as exosomes and microparticles. The stem cell secretome has most commonly been investigated in pre-clinical settings...
October 1, 2016: Apoptosis: An International Journal on Programmed Cell Death
Etsu Suzuki, Daishi Fujita, Masao Takahashi, Shigeyoshi Oba, Hiroaki Nishimatsu
Mesenchymal stem cells (MSCs) have been used to treat patients suffering from acute myocardial infarction (AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microRNAs...
September 26, 2016: World Journal of Stem Cells
Marina Morigi, Cinzia Rota, Giuseppe Remuzzi
Every year 13.3 million people suffer acute kidney injury (AKI), which is associated with a high risk of death or development of long-term chronic kidney disease (CKD) in a substantial percentage of patients besides other organ dysfunctions. To date, the mortality rate per year for AKI exceeds 50 % at least in patients requiring early renal replacement therapy and is higher than the mortality for breast and prostate cancer, heart failure and diabetes combined.Until now, no effective treatments able to accelerate renal recovery and improve survival post AKI have been developed...
2016: Methods in Molecular Biology
Anaïs Kervadec, Valérie Bellamy, Nadia El Harane, Lousineh Arakélian, Valérie Vanneaux, Isabelle Cacciapuoti, Hany Nemetalla, Marie-Cécile Périer, Hadi D Toeg, Adèle Richart, Mathilde Lemitre, Min Yin, Xavier Loyer, Jérôme Larghero, Albert Hagège, Marc Ruel, Chantal M Boulanger, Jean-Sébastien Silvestre, Philippe Menasché, Nisa K E Renault
BACKGROUND: Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell-derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways...
June 2016: Journal of Heart and Lung Transplantation
C R Campbell, A E Berman, N L Weintraub, Y L Tang
Injured or ischemic cardiac tissue has limited intrinsic capacity for regeneration. While stem cell transplantation is a promising approach to stimulating cardiac repair, its success in humans has thus far been limited. Harnessing the therapeutic benefits of stem cells requires a better understanding of their mechanisms of action and methods to optimize their function. Cardiac stem cells (CSC) represent a particularly effective cellular source for cardiac repair, and pre-conditioning CSC with electrical stimulation (EleS) was demonstrated to further enhance their function, although the mechanisms are unknown...
March 2016: Medical Hypotheses
Claudio Iaconetti, Sabato Sorrentino, Salvatore De Rosa, Ciro Indolfi
Micro-RNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression. Exosomes have recently emerged as novel elements of intercellular communication in the cardiovascular system. Exosomal miRNAs could be key players in intercellular cross-talk, particularly during different diseases such as myocardial infarction (MI) and heart failure (HF). This review addresses the functional role played by exosomal miRNAs in heart disease and their potential use as new biomarkers...
January 2016: Physiology
Philipp Pfeifer, Nikos Werner, Felix Jansen
Intercellular communication mediated by extracellular vesicles is crucial for preserving vascular integrity and in the development of cardiovascular disease. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes that can be found in almost every fluid compartment of the body like blood, saliva, and urine. In the recent years, a lot of reports came up suggesting that major cardiovascular and metabolic pathologies like atherogenesis, heart failure, or diabetes are highly influenced by transfer of microRNAs via extracellular vesicles leading to altered protein expression and phenotypes of recipient cells...
2015: BioMed Research International
A C H Pape, Maarten H Bakker, Cheyenne C S Tseng, Maartje M C Bastings, Stefan Koudstaal, Pierfrancesco Agostoni, Steven A J Chamuleau, Patricia Y W Dankers
Regeneration of lost myocardium is an important goal for future therapies because of the increasing occurrence of chronic ischemic heart failure and the limited access to donor hearts. An example of a treatment to recover the function of the heart consists of the local delivery of drugs and bioactives from a hydrogel. In this paper a method is introduced to formulate and inject a drug-loaded hydrogel non-invasively and side-specific into the pig heart using a long, flexible catheter. The use of 3-D electromechanical mapping and injection via a catheter allows side-specific treatment of the myocardium...
2015: Journal of Visualized Experiments: JoVE
Samarjit Das, Marc K Halushka
microRNAs (miRNAs) are a class of small regulatory RNAs that decrease protein translation to fine-tune cellular function. Recently, miRNAs were found to transfer from a donor cell into a recipient cell via exosomes and microparticles. These microvesicles are found in blood, urine, saliva, and other fluid compartments. miRNAs are delivered with intact functionality and have been repeatedly shown to regulate protein expression in recipient cells in a paracrine fashion. Thus, transported miRNAs are a new class of cell-to-cell regulatory species...
July 2015: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Suvi M Kuosmanen, Juha Hartikainen, Mikko Hippeläinen, Hannu Kokki, Anna-Liisa Levonen, Pasi Tavi
AIMS: Multicellular organisms maintain vital functions through intercellular communication. Release of extracellular vesicles that carry signals to even distant target organs is one way of accomplishing this communication. MicroRNAs can also be secreted from the cells in exosomes and act as paracrine signalling molecules. In addition, microRNAs have been implicated in the pathogenesis of a large number of diseases, including cardiovascular diseases, and are considered as promising candidate biomarkers due to their relative stability and easy quantification from clinical samples...
2015: PloS One
Takehiro Yamaguchi, Yasukatsu Izumi, Yasuhiro Nakamura, Takanori Yamazaki, Masayuki Shiota, Soichi Sano, Masako Tanaka, Mayuko Osada-Oka, Kenei Shimada, Katuyuki Miura, Minoru Yoshiyama, Hiroshi Iwao
BACKGROUND: Remote ischemic conditioning (RIC) by repeated treatment of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of reperfusion. In this study, we investigated the effects of repeated RIC on cardiac dysfunction after myocardial infarction (MI). METHODS AND RESULTS: At 4weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5cycles of 5min of bilateral hindlimb ischemia and 5min of reperfusion once a day for 4weeks...
January 15, 2015: International Journal of Cardiology
Julio Madrigal-Matute, Jes Sandal Lindholt, Carlos Ernesto Fernandez-Garcia, Alberto Benito-Martin, Elena Burillo, Guillermo Zalba, Oscar Beloqui, Patricia Llamas-Granda, Alberto Ortiz, Jesus Egido, Luis Miguel Blanco-Colio, Jose Luis Martin-Ventura
BACKGROUND: Galectin-3 (Gal-3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal-3 in cardiovascular (CV) diseases. The role of Gal-3 as a circulating biomarker has been demonstrated in patients with heart failure, but its importance as a biomarker in atherothrombosis is still unknown. METHODS AND RESULTS: Because Gal-3 is involved in monocyte-to-macrophage transition, we used fresh isolated monocytes and the in vitro model of macrophage differentiation of THP-1 cells stimulated with phorbol myristate acetate (PMA)...
August 2014: Journal of the American Heart Association
Claudia Bang, Sandor Batkai, Seema Dangwal, Shashi Kumar Gupta, Ariana Foinquinos, Angelika Holzmann, Annette Just, Janet Remke, Karina Zimmer, Andre Zeug, Evgeni Ponimaskin, Andreas Schmiedl, Xiaoke Yin, Manuel Mayr, Rashi Halder, Andre Fischer, Stefan Engelhardt, Yuanyuan Wei, Andreas Schober, Jan Fiedler, Thomas Thum
In response to stress, the heart undergoes extensive cardiac remodeling that results in cardiac fibrosis and pathological growth of cardiomyocytes (hypertrophy), which contribute to heart failure. Alterations in microRNA (miRNA) levels are associated with dysfunctional gene expression profiles associated with many cardiovascular disease conditions; however, miRNAs have emerged recently as paracrine signaling mediators. Thus, we investigated a potential paracrine miRNA crosstalk between cardiac fibroblasts and cardiomyocytes and found that cardiac fibroblasts secrete miRNA-enriched exosomes...
May 2014: Journal of Clinical Investigation
Ciro Indolfi, Antonio Curcio
Left ventricular hypertrophy is an initial compensatory mechanism in response to cardiac stress that can degenerate into heart failure and sudden cardiac death. Recent studies have shown that microRNAs (miRs) regulate several aspects of cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified an exosome-mediated communication mechanism between cardiac fibroblasts and cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes, which are subsequently taken up by cardiomyocytes, in which they alter gene expression...
May 2014: Journal of Clinical Investigation
Abderahim Gaceb, Maria Carmen Martinez, Ramaroson Andriantsitohaina
Extracellular vesicles, particles released by all cell types, represent a new way to convey information between cells such as proteins, second messengers, and genetic information to modify the phenotype and function of the target cells. Recent data suggest that extracellular vesicles play a crucial role in both physiology and pathology, including coagulation, angiogenesis, cell survival, modulation of the immune response, and inflammation. Thus extracellular vesicles participate in the processes of cardiovascular diseases from atherosclerosis, myocardial infarction to heart failure...
May 2014: International Journal of Biochemistry & Cell Biology
Sen Matsumoto, Yasuhiko Sakata, Shinichiro Suna, Daisaku Nakatani, Masaya Usami, Masahiko Hara, Tetsuhisa Kitamura, Toshimitsu Hamasaki, Shinsuke Nanto, Yukio Kawahara, Issei Komuro
RATIONALE: Despite a recent decline of in-hospital mortality attributable to acute myocardial infarction (AMI), the incidence of ischemic heart failure (HF) in post-AMI patients is increasing. Although various microRNAs have been proposed as diagnostic indicators for AMI, no microRNAs have been established as predictors of ischemic HF that develops after AMI. OBJECTIVE: We attempted to identify circulating microRNAs that can serve as reliable predictors of ischemic HF in post-AMI patients...
July 19, 2013: Circulation Research
Ying Yang, Jessica E Rodriguez, Richard N Kitsis
For decades, peripartum cardiomyopathy has remained an enigma. Despite extensive research, our understanding of how a previously healthy woman can develop lethal heart failure in the context of pregnancy remains vague. Recent work suggests that inadequacy of the cardiac microvasculature may be the primary abnormality and has implicated an antiangiogenic fragment of the nursing hormone prolactin as playing an important role. In this issue of the JCI, Halkein et al. explore signaling downstream of this prolactin fragment and demonstrate that miR-146a is a critical mediator of the antiangiogenic effects in endothelial cells...
May 2013: Journal of Clinical Investigation
Parveen Sharma, Jake Cosme, Anthony O Gramolini
Cardiovascular diseases (CVDs) are the major source of global morbidity and death and more people die annually from CVDs than from any other cause. These diseases can occur quickly, as seen in acute myocardial infarction (AMI), or progress slowly over years as with chronic heart failure. Advances in mass spectrometry detection and analysis, together with improved isolation and enrichment techniques allowing for the separation of organelles and membrane proteins, now allow for the indepth analysis of the cardiac proteome...
April 9, 2013: Journal of Proteomics
M Judith Radin, Ming-Jiun Yu, Lene Stoedkilde, R Lance Miller, Jason D Hoffert, Jorgen Frokiaer, Trairak Pisitkun, Mark A Knepper
Aquaporin-2 (AQP2), the vasopressin-regulated water channel of the renal collecting duct, is dysregulated in numerous disorders of water balance in people and animals, including those associated with polyuria (urinary tract obstruction, hypokalemia, inflammation, and lithium toxicity) and with dilutional hyponatremia (syndrome of inappropriate antidiuresis, congestive heart failure, cirrhosis). Normal regulation of AQP2 by vasopressin involves 2 independent regulatory mechanisms: (1) short-term regulation of AQP2 trafficking to and from the apical plasma membrane, and (2) long-term regulation of the total abundance of the AQP2 protein in the cells...
December 2012: Veterinary Clinical Pathology
Changjin Lee, S Alex Mitsialis, Muhammad Aslam, Sally H Vitali, Eleni Vergadi, Georgios Konstantinou, Konstantinos Sdrimas, Angeles Fernandez-Gonzalez, Stella Kourembanas
BACKGROUND: Hypoxia induces an inflammatory response in the lung manifested by alternative activation of macrophages with elevation of proinflammatory mediators that are critical for the later development of hypoxic pulmonary hypertension. Mesenchymal stromal cell transplantation inhibits lung inflammation, vascular remodeling, and right heart failure and reverses hypoxic pulmonary hypertension in experimental models of disease. In this study, we aimed to investigate the paracrine mechanisms by which mesenchymal stromal cells are protective in hypoxic pulmonary hypertension...
November 27, 2012: Circulation
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