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Journal of Cardiovascular Translational Research

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https://www.readbyqxmd.com/read/28289983/stem-cell-spheroids-and-ex-vivo-niche-modeling-rationalization-and-scaling-up
#1
REVIEW
Isotta Chimenti, Diana Massai, Umberto Morbiducci, Antonio Paolo Beltrami, Maurizio Pesce, Elisa Messina
Improved protocols/devices for in vitro culture of 3D cell spheroids may provide essential cues for proper growth and differentiation of stem/progenitor cells (S/PCs) in their niche, allowing preservation of specific features, such as multi-lineage potential and paracrine activity. Several platforms have been employed to replicate these conditions and to generate S/PC spheroids for therapeutic applications. However, they incompletely reproduce the niche environment, with partial loss of its highly regulated network, with additional hurdles in the field of cardiac biology, due to debated resident S/PCs therapeutic potential and clinical translation...
March 13, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28281243/mimicking-cardiac-fibrosis-in-a-dish-fibroblast-density-rather-than-collagen-density-weakens-cardiomyocyte-function
#2
Ariane C C van Spreeuwel, Noortje A M Bax, Bastiaan J van Nierop, Annemieke Aartsma-Rus, Marie-José T H Goumans, Carlijn V C Bouten
Cardiac fibrosis is one of the most devastating effects of cardiac disease. Current in vitro models of cardiac fibrosis do not sufficiently mimic the complex in vivo environment of the cardiomyocyte. We determined the local composition and mechanical properties of the myocardium in established mouse models of genetic and acquired fibrosis and tested the effect of myocardial composition on cardiomyocyte contractility in vitro by systematically manipulating the number of fibroblasts and collagen concentration in a platform of engineered cardiac microtissues...
March 9, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28281242/regulation-of-a-kinase-anchoring-protein-12-by-heat-shock-protein-a12b-to-prevent-ventricular-dysfunction-following-acute-myocardial-infarction-in-diabetic-rats
#3
Vaithinathan Selvaraju, Sumanth C Suresh, Mahesh Thirunavukkarasu, Jayakanthan Mannu, Jocelyn L C Foye, Premendu P Mathur, J Alexander Palesty, Juan A Sanchez, David W McFadden, Nilanjana Maulik
We examined the effects of overexpressing HSPA12B on angiogenesis and myocardial function by intramyocardial administration of adenovirus encoding HSPA12B (Ad. HSPA12B) in a streptozotocin-induced diabetic rat subjected to myocardial infarction. Rats were divided randomly into six groups: control sham (CS) + Ad.LacZ, control myocardial infarction (CMI) + Ad.LacZ, control MI + Ad.HSPA12B, diabetic sham (DS) + Ad.LacZ, diabetic MI + Ad.LacZ and diabetic MI + Ad.HSPA12B. Following MI or sham surgery, the respective groups received either Ad...
March 9, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28281241/decellularized-cryopreserved-allografts-as-off-the-shelf-allogeneic-alternative-for-heart-valve-replacement-in-vitro-assessment-before-clinical-translation
#4
Laura Iop, Adolfo Paolin, Paola Aguiari, Diletta Trojan, Elisa Cogliati, Gino Gerosa
Cryopreserved allogeneic conduits are the elective biocompatible choice among currently available substitutes for surgical replacement in end-stage valvulopathy. However, degeneration occurs in 15 years in adults or faster in children, due to recipient's immunological reactions to donor's antigens. Here, human aortic valves were decellularized by TRICOL, based on Triton X-100 and sodium cholate, and submitted to standard cryopreservation (TRICOL-human aortic valves (hAVs)). Tissue samples were analyzed to study the effects of the combined procedure on original valve architecture and donor's cell removal...
March 9, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28281240/translational-challenges-in-cardiovascular-tissue-engineering
#5
Maximilian Y Emmert, Emanuela S Fioretta, Simon P Hoerstrup
Valvular heart disease and congenital heart defects represent a major cause of death around the globe. Although current therapy strategies have rapidly evolved over the decades and are nowadays safe, effective, and applicable to many affected patients, the currently used artificial prostheses are still suboptimal. They do not promote regeneration, physiological remodeling, or growth (particularly important aspects for children) as their native counterparts. This results in the continuous degeneration and subsequent failure of these prostheses which is often associated with an increased morbidity and mortality as well as the need for multiple re-interventions...
March 9, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28265882/cardiovascular-bio-engineering-current-state-of-the-art
#6
REVIEW
Teresa Simon-Yarza, Isabelle Bataille, Didier Letourneur
Despite the introduction of new drugs and innovative devices contributing in the last years to improve patients' quality of life, morbidity and mortality from cardiovascular diseases remain high. There is an urgent need for addressing the underlying problem of the loss of cardiac or vascular tissues and therefore developing new therapies. Autologous vascular transplants are often limited by poor quality of donor sites and heart organ transplantation by donor shortage. Vascular and cardiac tissue engineering, whose aim is to repair or replace cardiovascular tissues by the use of cells, engineering and materials, as well as biochemical and physicochemical factors, appears in this scenario as a promising tool to repair the damaged hearts and vessels...
March 6, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28258421/phenomapping-for-the-identification-of-hypertensive-patients-with-the-myocardial-substrate-for-heart-failure-with-preserved-ejection-fraction
#7
Daniel H Katz, Rahul C Deo, Frank G Aguilar, Senthil Selvaraj, Eva E Martinez, Lauren Beussink-Nelson, Kwang-Youn A Kim, Jie Peng, Marguerite R Irvin, Hemant Tiwari, D C Rao, Donna K Arnett, Sanjiv J Shah
We sought to evaluate whether unbiased machine learning of dense phenotypic data ("phenomapping") could identify distinct hypertension subgroups that are associated with the myocardial substrate (i.e., abnormal cardiac mechanics) for heart failure with preserved ejection fraction (HFpEF). In the HyperGEN study, a population- and family-based study of hypertension, we studied 1273 hypertensive patients utilizing clinical, laboratory, and conventional echocardiographic phenotyping of the study participants. We used machine learning analysis of 47 continuous phenotypic variables to identify mutually exclusive groups constituting a novel classification of hypertension...
March 3, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28213846/fixation-of-bovine-pericardium-based-tissue-biomaterial-with-irreversible-chemistry-improves-biochemical-and-biomechanical-properties
#8
H Tam, W Zhang, D Infante, N Parchment, M Sacks, N Vyavahare
Bioprosthetic heart valves (BHVs), derived from glutaraldehyde crosslinked (GLUT) porcine aortic valve leaflets or bovine pericardium (BP), are used to replace defective heart valves. However, valve failure can occur within 12-15 years due to calcification and/or progressive structural degeneration. We present a novel fabrication method that utilizes carbodiimide, neomycin trisulfate, and pentagalloyl glucose crosslinking chemistry (TRI) to better stabilize the extracellular matrix of BP. We demonstrate that TRI-treated BP is more compliant than GLUT-treated BP...
February 17, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28210939/deep-phenotyping-of-systemic-arterial-hemodynamics-in-hfpef-part-1-physiologic-and-technical-considerations
#9
REVIEW
Julio A Chirinos
A better understanding of the pathophysiology of heart failure with a preserved left ventricular ejection fraction (HFpEF) is important. Detailed phenotyping of pulsatile hemodynamics has provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, microvascular disease, and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance, the cardinal feature of HFpEF. Furthermore, arterial pulsatile hemodynamic mechanisms likely contribute to the frequent presence of comorbidities, such as renal failure and dementia, in this population...
February 16, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28205013/utilizing-the-foreign-body-response-to-grow-tissue-engineered-blood-vessels-in-vivo
#10
Wouter J Geelhoed, Lorenzo Moroni, Joris I Rotmans
It is well known that the number of patients requiring a vascular grafts for use as vessel replacement in cardiovascular diseases, or as vascular access site for hemodialysis is ever increasing. The development of tissue engineered blood vessels (TEBV's) is a promising method to meet this increasing demand vascular grafts, without having to rely on poorly performing synthetic options such as polytetrafluoroethylene (PTFE) or Dacron. The generation of in vivo TEBV's involves utilizing the host reaction to an implanted biomaterial for the generation of completely autologous tissues...
February 15, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28116551/tensor-factorization-for-precision-medicine-in-heart-failure-with-preserved-ejection-fraction
#11
Yuan Luo, Faraz S Ahmad, Sanjiv J Shah
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that may benefit from improved subtyping in order to better characterize its pathophysiology and to develop novel targeted therapies. The United States Precision Medicine Initiative comes amid the rapid growth in quantity and modality of clinical data for HFpEF patients ranging from deep phenotypic to trans-omic data. Tensor factorization, a form of machine learning, allows for the integration of multiple data modalities to derive clinically relevant HFpEF subtypes that may have significant differences in underlying pathophysiology and differential response to therapies...
January 23, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28105587/phenotype-specific-association-of-single-nucleotide-polymorphisms-with-heart-failure-and-preserved-ejection-fraction-a-genome-wide-association-analysis-of-the-cardiovascular-health-study
#12
David P Kao, Laura M Stevens, Michael A Hinterberg, Carsten Görg
Little is known about genetics of heart failure with preserved ejection fraction (HFpEF) in part because of the many comorbidities in this population. To identify single-nucleotide polymorphisms (SNPs) associated with HFpEF, we analyzed phenotypic and genotypic data from the Cardiovascular Health Study, which profiled patients using a 50,000 SNP array. Results were explored using novel SNP- and gene-centric tools. We performed analyses to determine whether some SNPs were relevant only in certain phenotypes...
January 19, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28097523/intravascular-ultrasound-characterization-of-a-tissue-engineered-vascular-graft-in-an-ovine-model
#13
Victoria K Pepper, Elizabeth S Clark, Cameron A Best, Ekene A Onwuka, Tadahisa Sugiura, Eric D Heuer, Lilamarie E Moko, Shinka Miyamoto, Hideki Miyachi, Darren P Berman, Sharon L Cheatham, Joanne L Chisolm, Toshiharu Shinoka, Christopher K Breuer, John P Cheatham
Patients who undergo implantation of a tissue-engineered vascular graft (TEVG) for congenital cardiac anomalies are monitored with echocardiography, followed by magnetic resonance imaging or angiography when indicated. While these methods provide data regarding the lumen, minimal information regarding neotissue formation is obtained. Intravascular ultrasound (IVUS) has previously been used in a variety of conditions to evaluate the vessel wall. The purpose of this study was to evaluate the utility of IVUS for evaluation of TEVGs in our ovine model...
January 17, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28168652/impaired-tissue-oxygenation-in-metabolic-syndrome-requires-increased-microvascular-perfusion-heterogeneity
#14
P Mason McClatchey, Fan Wu, I Mark Olfert, Christopher G Ellis, Daniel Goldman, Jane E B Reusch, Jefferson C Frisbee
Metabolic syndrome (MS) in obese Zucker rats (OZR) is associated with impaired skeletal muscle performance and blunted hyperemia. Studies suggest that reduced O2 diffusion capacity is required to explain compromised muscle performance and that heterogeneous microvascular perfusion distribution is critical. We modeled tissue oxygenation during muscle contraction in control and OZR skeletal muscle using physiologically realistic relationships. Using a network model of Krogh cylinders with increasing perfusion asymmetry and increased plasma skimming, we predict increased perfusion heterogeneity and decreased muscle oxygenation in OZR, with partial recovery following therapy...
February 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28138913/usefulness-of-genetic-testing-in-hypertrophic-cardiomyopathy-an-analysis-using-real-world-data
#15
M Alejandra Restrepo-Cordoba, Oscar Campuzano, Tomás Ripoll-Vera, Marta Cobo-Marcos, Irene Mademont-Soler, José M Gámez, Fernando Dominguez, Esther Gonzalez-Lopez, Laura Padron-Barthe, Enrique Lara-Pezzi, Luis Alonso-Pulpon, Ramon Brugada, Pablo Garcia-Pavia
This study sought to determine the usefulness of genetic testing to predict evolution in hypertrophic cardiomyopathy (HCM) and to assess the role of genetic testing in clinical practice. Genetic results of 100 HCM patients tested for mutations in ≥10 HCM-causing genes were evaluated. Patients were classified as with poor (group A) or favourable (group B) clinical course. Forty-five pathogenic mutations (PM) were identified in 28 patients (56 %) from group A and in 23 (46 %) from group B (p = 0.317). Only 40 patients (40 %) exhibited PM that had been previously reported and only 15 (15 %) had PM reported in ≥10 individuals...
February 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28116550/implantation-of-a-poly-l-lactide-gcsf-functionalized-scaffold-in-a-model-of-chronic-myocardial-infarction
#16
Cristiano Spadaccio, Francesco Nappi, Federico De Marco, Pietro Sedati, Chiara Taffon, Antonio Nenna, Anna Crescenzi, Massimo Chello, Marcella Trombetta, Ivancarmine Gambardella, Alberto Rainer
A previously developed poly-L-lactide scaffold releasing granulocyte colony-stimulating factor (PLLA/GCSF) was tested in a rabbit chronic model of myocardial infarction (MI) as a ventricular patch. Control groups were constituted by healthy, chronic MI and nonfunctionalized PLLA scaffold. PLLA-based electrospun scaffold efficiently integrated into a chronic infarcted myocardium. Functionalization of the biopolymer with GCSF led to increased fibroblast-like vimentin-positive cellular colonization and reduced inflammatory cell infiltration within the micrometric fiber mesh in comparison to nonfunctionalized scaffold; PLLA/GCSF polymer induced an angiogenetic process with a statistically significant increase in the number of neovessels compared to the nonfunctionalized scaffold; PLLA/GCSF implanted at the infarcted zone induced a reorganization of the ECM architecture leading to connective tissue deposition and scar remodeling...
February 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28097522/severe-aortic-valve-stenosis-in-adults-is-associated-with-increased-levels-of-circulating-intermediate-monocytes
#17
Bernd Hewing, Sebastian Chi-Diep Au, Antje Ludwig, Rena Ellerbroek, Phillip van Dijck, Lisa Hartmann, Herko Grubitzsch, Carolin Giannini, Michael Laule, Verena Stangl, Gert Baumann, Karl Stangl
Individual monocyte subsets have been associated with atherosclerotic disease, but their distribution has not been evaluated in aortic valve stenosis (AS) so far. In the present study, we have asked whether levels of the circulating intermediate monocyte subset are increased in AS. Classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) CD86-positive monocytes and monocyte activation (intensity of CD11b expression) were determined by flow cytometry in peripheral blood of patients with severe AS (n = 100) and matched AS-free controls (n = 75)...
February 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28035653/non-classical-monocytes-levels-increased-by-subcutaneous-fat-secretome-are-associated-with-less-rehospitalization-after-heart-failure-admission
#18
Sonia Eiras, Alfonso Varela-Román, Mariléia Cháves Andrade, Ana Castro, Rocío González-Ferreiro, Juan E Viñuela, Ángel Fernández-Trasancos, Marcos C Carreira, Ezequiel Álvarez, Felipe F Casanueva, José R González-Juanatey
Differential monocyte subsets are increased in obesity and heart failure (HF). We studied their role as predictors of rehospitalization for HF and their regulation by adipose tissue. Monocyte subsets and body fat composition were determined from 136 patients at the discharge after HF admission. Regulation of monocytes by SAT secretomes from obese/non-obese patients with HF was studied in a cell culture method. Proteomic analysis of secretome SAT was performed by LC-MALDI TOF/TOF. High CD14(-)CD16(+) monocyte levels indicated less rehospitalization for HF (p = 0...
February 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28028693/a-study-of-coronary-bifurcation-shape-in-a-normal-population
#19
Pau Medrano-Gracia, John Ormiston, Mark Webster, Susann Beier, Chris Ellis, Chunliang Wang, Örjan Smedby, Alistair Young, Brett Cowan
During percutaneous coronary intervention, stents are placed in narrowings of the arteries to restore normal blood flow. Despite improvements in stent design, deployment techniques and drug-eluting coatings, restenosis and stent thrombosis remain a significant problem. Population stent design based on statistical shape analysis may improve clinical outcomes. Computed tomographic (CT) coronary angiography scans from 211 patients with a zero calcium score, no stenoses and no intermediate artery, were used to create statistical shape models of 446 major coronary artery bifurcations (left main, first diagonal and obtuse marginal and right coronary crux)...
February 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28028691/sirolimus-therapy-is-associated-with-elevation-in-circulating-pcsk9-levels-in-cardiac-transplant-patients
#20
Vinaya Simha, Sisi Qin, Pankaj Shah, Byron H Smith, Walter K Kremers, Sudhir Kushwaha, Liewei Wang, Naveen L Pereira
Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0...
February 2017: Journal of Cardiovascular Translational Research
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