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Circulation Research

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https://www.readbyqxmd.com/read/28096195/the-multifunctional-mitochondrial-epac1-controls-myocardial-cell-death
#1
Loubina Fazal, Marion Laudette, Sílvia Paula-Gomes, Sandrine Pons, Caroline Conte, Florence Tortosa, Pierre Sicard, Yannis Sainte-Marie, Malik Bisserier, Olivier Lairez, Alexandre Lucas, Jérôme Roy, Bijan Ghaleh, Jeremy Fauconnier, Jeanne Mialet-Perez, Frank Lezoualc'h
RATIONALE: Although the second messenger cyclic AMP (cAMP) is physiologically beneficial in the heart, it largely contributes to cardiac disease progression when dysregulated. Current evidence suggests that cAMP is produced within mitochondria. However, mitochondrial cAMP signaling and its involvement in cardiac pathophysiology are far from being understood. OBJECTIVE: To investigate the role of mitochondrial exchange protein directly activated by cAMP 1 (MitEpac1) in ischemia/reperfusion (I/R) injury...
January 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28096194/autologous-cell-therapy-for-peripheral-arterial-disease-systematic-review-and-meta-analysis-of-randomized-non-randomized-and-non-controlled-studies
#2
Mauro Rigato, Matteo Monami, Gian Paolo Fadini
RATIONALE: Critical limb ischemia (CLI) is a life-threatening complication of peripheral arterial disease (PAD). In patients who are ineligible for revascularization procedures, there are few therapeutic alternatives, leading to amputations and death. OBJECTIVE: To provide a systematic review of the literature and a meta-analysis of studies evaluating safety and efficacy of autologous cell therapy for intractable PAD/CLI. METHODS AND RESULTS: We retrieved 19 randomized controlled trials (RCTs; 837 patients), 7 non-randomized trials (338 patients), and 41 non-controlled studies (1,177 patients)...
January 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28077443/single-dose-intracardiac-injection-of-pro-regenerative-micrornas-improves-cardiac-function-after-myocardial-infarction
#3
Pierluigi Lesizza, Giulia Prosdocimo, Valentina Martinelli, Gianfranco Sinagra, Serena Zacchigna, Mauro Giacca
RATIONALE: Recent evidence indicates that a few human microRNAs (miRNAs), in particular hsa-miR-199a-3p and hsa-miR-590-3p, stimulate proliferation of cardiomyocytes and, once expressed in the mouse heart using viral vectors, induce cardiac regeneration after myocardial infarction. Viral vectors, however, are not devoid of safety issues and, more notably, drive expression of the encoded miRNAs for indefinite periods of time, which might not be desirable in light of human therapeutic application...
January 11, 2017: Circulation Research
https://www.readbyqxmd.com/read/28073804/hemodynamic-support-with-a-micro-axial-percutaneous-left-ventricular-assist-device-impella%C3%A2-protects-against-acute-kidney-injury-in-patients-undergoing-high-risk-percutaneous-coronary-intervention
#4
Michael P Flaherty, Sadip Pant, Samir V Patel, Tyler Kilgore, Sujith Dassanayaka, John Loughran, Wasiq Rawasia, Buddhadeb Dawn, Allen Cheng, Carlo R Bartoli
RATIONALE: Acute kidney injury (AKI) is common during high-risk percutaneous coronary intervention (PCI) particularly in those with severely reduced left ventricular (LV) ejection fraction (EF). The impact of partial hemodynamic support with a micro-axial percutaneous LV assist device (pLVAD) on renal function following high-risk PCI remains unknown. OBJECTIVE: We tested the hypothesis that partial hemodynamic support with the Impella 2.5 micro-axial pLVAD during high-risk PCI protected against AKI...
January 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28069694/myocardial-tissue-engineering-with-cells-derived-from-human-induced-pluripotent-stem-cells-and-a-native-like-high-resolution-3-dimensionally-printed-scaffold
#5
Ling Gao, Molly Kupfer, Jangwook Jung, Libang Yang, Patrick Zhang, Yong Sie, Quyen Tran, Visar Ajeti, Brian Freeman, Vladimir Fast, Paul Campagnola, Brenda Ogle, Jianyi Zhang
RATIONALE: Conventional three-dimensional (3D) printing techniques cannot produce structures of the size at which individual cells interact. OBJECTIVE: Here, we used multiphoton-excited, 3-dimensional printing (MPE-3DP) to generate a native-like, extracellular matrix (ECM) scaffold with submicron resolution, and then seeded the scaffold with cardiomyocytes (CMs), smooth-muscle cells (SMCs), and endothelial cells (ECs) that had been differentiated from human induced-pluripotent stem cells (iPSCs) to generate a human, iPSC-derived cardiac muscle patch (hCMP), which was subsequently evaluated in a murine model of myocardial infarction (MI)...
January 9, 2017: Circulation Research
https://www.readbyqxmd.com/read/28052915/intracoronary-cardiac-progenitor-cells-in-single-ventricle-physiology-the-perseus-randomized-phase-2-trial
#6
Shuta Ishigami, Shinichi Ohtsuki, Takahiro Eitoku, Daiki Ousaka, Maiko Kondo, Yoshihiko Kurita, Kenta Hirai, Yosuke Fukushima, Kenji Baba, Takuya Goto, Naohiro Horio, Junko Kobayashi, Yosuke Kuroko, Yasuhiro Kotani, Sadahiko Arai, Tatsuo Iwasaki, Shuhei Sato, Shingo Kasahara, Shunji Sano, Hidemasa Oh
RATIONALE: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. OBJECTIVE: To determine if intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. METHODS AND RESULTS: We conducted a phase 2 randomized controlled study to assign 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-2 or -3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A)...
January 4, 2017: Circulation Research
https://www.readbyqxmd.com/read/28031416/route-of-delivery-modulates-the-efficacy-of-mesenchymal-stem-cell-therapy-for-myocardial-infarction-a-meta-analysis-of-preclinical-studies-and-clinical-trials
#7
Anthony Kanelidis, Courtney Premer, Juan G Lopez, Wayne Balkan, Joshua M Hare
RATIONALE: Accumulating data supports a therapeutic role for mesenchymal stem cell (MSC) therapy; however, there is no consensus on the optimal route of delivery. OBJECTIVE: We tested the hypothesis that the route of MSC delivery influences the reduction in infarct size (IS) and improvement in left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We performed a meta-analysis investigating the effect of MSC therapy in acute myocardial infarction (AMI) and chronic ischemic cardiomyopathy (ICM) preclinical studies (58 studies; n=1165 mouse, rat, swine) which revealed a reduction in IS and improvement of LVEF in all animal models...
December 28, 2016: Circulation Research
https://www.readbyqxmd.com/read/28003220/recycling-of-apolipoprotein-a-after-plgrkt-mediated-endocytosis-of-lipoprotein-a
#8
Monika Sharma, Gregory M Redpath, Michael J Williams, Sally P McCormick
RATIONALE: Lipoprotein(a) [Lp(a)] is a low density lipoprotein (LDL)-like lipoprotein and important cardiovascular risk factor whose cognate receptor and intracellular fate remains unknown. OBJECTIVE: Our study aimed to determine the intracellular trafficking pathway for Lp(a) and the receptor responsible for its uptake in liver cells. METHODS AND RESULTS: Human hepatoma (HepG2) cells were treated with Lp(a) purified from human plasma and Lp(a) uptake studied using western blot analysis and intracellular localisation of Lp(a) by confocal microscopy...
December 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/28003219/direct-reprogramming-of-human-dermal-fibroblasts-into-endothelial-cells-using-er71-etv2
#9
Sangho Lee, Changwon Park, Ji W Han, Ju Young Kim, Kyuwon Cho, Eun Jae Kim, Sangsung Kim, Shin-Jeong Lee, Se-Yeong Oh, Yoshiaki Tanaka, In-Hyun Park, Hyo Jae An, Claire M Shin, Shraya Sharma, Young-Sup Yoon
RATIONALE: Direct conversion or reprogramming of human postnatal cells into endothelial cells (ECs), bypassing stem or progenitor cell status, is crucial for regenerative medicine, cell therapy, and pathophysiological investigation but has remained largely unexplored. OBJECTIVE: We sought to directly reprogram human postnatal dermal fibroblasts (HDFs) to ECs with vasculogenic and endothelial transcription factors (TFs) and determine their vascularizing and therapeutic potential...
December 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27974423/vegf165b-modulates-endothelial-vegfr1-stat3-signaling-pathway-and-angiogenesis-in-human-and-experimental-peripheral-arterial-disease
#10
Vijay C Ganta, Min Choi, Anna Kutateladze, Brian H Annex
RATIONALE: Atherosclerotic-arterial occlusions decrease tissue perfusion causing ischemia to lower limbs in patients with peripheral arterial disease (PAD). Ischemia in muscle induces an angiogenic response but the magnitude of this response is frequently inadequate to meet tissue perfusion requirements. Alternate splicing in the exon-8 of vascular endothelial growth factor (VEGF)-A results in production of pro-angiogenic VEGFxxxa isoforms (VEGF165a, 165 for the 165 amino acid product) and anti-angiogenic VEGFxxxb (VEGF165b) isoforms...
December 14, 2016: Circulation Research
https://www.readbyqxmd.com/read/27956416/telomere-shortening-regenerative-capacity-and-cardiovascular-outcomes
#11
Muhammad Hammadah, Ibhar Al Mheid, Kobina Wilmot, Ronnie Ramadan, Naser Abdulhadi, Ayman Alkhoder, Malik Obideen, Pratik Pimple, Oleksiy Levantsevych, Heval Kelli, Amit Shah, Yan Sun, Brad Pearce, Michael Kutner, Qi Long, Laura Ward, Yi-An Ko, Kareem Hosny Mohammed, Jue Lin, Jinying Zhao, J Bremner, Jinhee Kim, Edmund Waller, Paolo Raggi, David Sheps, Arshed Quyyumi, Viola Vaccarino
RATIONALE: Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration. OBJECTIVE: To examine the relationship between LTL and PCs, and their impact on adverse cardiovascular outcomes. METHODS AND RESULTS: We measured LTL by quantitative PCR in 566 outpatients (age 63±9 years, 76% male) with coronary artery disease (CAD)...
December 12, 2016: Circulation Research
https://www.readbyqxmd.com/read/27932512/atf6-decreases-myocardial-ischemia-reperfusion-damage-and-links-er-stress-and-oxidative-stress-signaling-pathways-in-the-heart
#12
Jung-Kang Jin, Erik A Blackwood, Khalid M Azizi, Donna J Thuerauf, Asal G Fahem, Christoph Hofmann, Randal J Kaufman, Shirin Doroudgar, Christopher C Glembotski
RATIONALE: ER stress causes accumulation of misfolded proteins in the ER, activating the transcription factor, ATF6, which induces ER stress response genes. Myocardial ischemia induces the ER stress response; however, neither the function of this response nor whether it is mediated by ATF6 is known. OBJECTIVE: Here, we examined the effects of blocking the ATF6-mediated ER stress response on ischemia/reperfusion (I/R) in cardiac myocytes and mouse hearts. METHODS AND RESULTS: Knockdown of ATF6 in cardiac myocytes subjected to I/R increased ROS and necrotic cell death, which were mitigated by ATF6 overexpression...
December 8, 2016: Circulation Research
https://www.readbyqxmd.com/read/27927683/pharmacokinetics-and-pharmacodynamics-of-inorganic-nitrate-in-heart-failure-with-preserved-ejection-fraction
#13
Payman Zamani, Victor X Tan, Haideliza Soto-Calderon, Melissa Beraun, Jeffrey Brandimarto, Lien Trieu, Swapna Varakantam, Paschalis-Thomas Doulias, Raymond R Townsend, Jesse Chittams, Kenneth B Margulies, Thomas P Cappola, David C Poole, Harry Ischiropoulos, Julio A Chirinos
RATIONALE: Nitrate-rich beetroot juice has been shown to improve exercise capacity in Heart Failure with Preserved Ejection Fraction (HFpEF), but studies using pharmacologic preparations of inorganic nitrate are lacking. OBJECTIVE: To determine: (1) the dose-response effect of potassium nitrate (KNO3) on exercise capacity; (2) the population-specific pharmacokinetic and safety profile of KNO3 in HFpEF. METHODS AND RESULTS: We randomized 12 subjects with HFpEF to oral KNO3 (n=9) or potassium chloride (KCl, n=3)...
December 7, 2016: Circulation Research
https://www.readbyqxmd.com/read/27923814/mir-483-targeting-of-ctgf-suppresses-endothelial-to-mesenchymal-transition-therapeutic-implications-in-kawasaki-disease
#14
Ming He, Zhen Chen, Marcy Martin, Jin Zhang, Panjamaporn Sangwung, Brian Woo, Adriana Tremoulet, Chisato Shimizu, Mukesh K Jain, Jane C Burns, John Shyy
RATIONALE: Endothelial-to-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD. OBJECTIVE: We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis...
December 6, 2016: Circulation Research
https://www.readbyqxmd.com/read/27920123/selective-enhancement-of-insulin-sensitivity-in-the-endothelium-in-vivo-reveals-a-novel-proatherosclerotic-signalling-loop
#15
Hema Viswambharan, Nadira Y Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C Gage, Natalie J Haywood, Andrew M Walker, Anna Skromna, Natalia Makova, Stacey L Galloway, Pooja Shah, Piruthivi Sukumar, Karen E Porter, Peter J Grant, Ajay M Shah, Celio X Santos, Jing Li, David J Beech, Stephen Wheatcroft, Richard M Cubbon, Mark T Kearney
RATIONALE: In the endothelium, insulin stimulates endothelial nitric oxide synthase (eNOS) to generate the anti-atherosclerotic signalling radical NO. Insulin resistant type 2 diabetes is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. OBJECTIVE: To answer this question we generated a mouse with endothelial cell (EC)-specific over-expression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer...
December 5, 2016: Circulation Research
https://www.readbyqxmd.com/read/27920122/microrna-33-controls-adaptive-fibrotic-response-in-the-remodeling-heart-by-preserving-lipid-raft-cholesterol
#16
Masataka Nishiga, Takahiro Horie, Yasuhide Kuwabara, Kazuya Nagao, Osamu Baba, Tetsushi Nakao, Tomohiro Nishino, Daihiko Hakuno, Yasuhiro Nakashima, Hitoo Nishi, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Masahiro Kimura, Ritsuko Hanada, Tomoyuki Nakamura, Tsukasa Inada, Koji Hasegawa, Simon J Conway, Toru Kita, Takeshi Kimura, Koh Ono
RATIONALE: Heart failure (HF) and atherosclerosis share the underlying mechanisms of chronic inflammation followed by fibrosis. A highly conserved microRNA (miR), miR-33 is considered as a potential therapeutic target for atherosclerosis because it regulates lipid metabolism and inflammation. However, the role of miR-33 in HF remains to be elucidated. OBJECTIVE: To clarify the role of miR-33 involved in HF. METHODS AND RESULTS: We first investigated the expression levels of miR-33a/b in human cardiac tissue samples with dilated cardiomyopathy...
December 5, 2016: Circulation Research
https://www.readbyqxmd.com/read/27908912/a-deep-proteome-analysis-identifies-the-complete-secretome-as-the-functional-unit-of-human-cardiac-progenitor-cells
#17
Sudhish Sharma, Rachana Mishra, Grace E Bigham, Brody Wehman, Mohd M Khan, Huichun Xu, Progyaparamita Saha, Young Ah Goo, Srinivisa R Datla, Ling Chen, Mohan E Tulapurkar, Bradley S Taylor, Peixin Yang, Sotirios K Karathanasis, David R Goodlett, Sunjay Kaushal
RATIONALE: Cardiac progenitor cells are an attractive cell type for tissue regeneration but their mechanism for myocardial remodeling is still unclear. OBJECTIVE: This investigation determines how chronological age influences the phenotypic characteristics and the secretome of human cardiac progenitor cells (CPCs), as well as their potential to recover injured myocardium. METHODS AND RESULTS: Adult (aCPCs) and neonatal (nCPCs) cells were derived from patients more than 40 years or less than one month of age, respectively, and their functional potential was determined in a rodent myocardial infarction (MI) model...
December 1, 2016: Circulation Research
https://www.readbyqxmd.com/read/27903568/effects-of-trans-endocardial-delivery-of-bone-marrow-derived-cd133-cells-on-left-ventricle-perfusion-and-function-in-patients-with-refractory-angina-final-results-of-randomized-double-blinded-placebo-controlled-regent-vsel-trial
#18
Wojciech Wojakowski, Tomasz Jadczyk, Aleksandra Michalewska-Wludarczyk, Zofia Parma, Miroslaw Markiewicz, Wojciech Rychlik, Magdalena Kostkiewicz, Katarzyna Gruszczynska, Anna Blach, Monika Dzierzak-Mietla, Wojciech Wanha, Joanna Ciosek, Beata Ochala, Lukasz Rzeszutko, Wieslaw Cybulski, Lukasz Partyka, Wojciech Zasada, Witold Wludarczyk, Sebastian Dworowy, Waclaw B Kuczmik, Grzegorz Smolka, Tomasz Z Pawlowski, Andrzej Ochala, Michal Tendera
RATIONALE: New therapies for refractory angina are needed. OBJECTIVE: Assessment of trans-endocardial delivery of bone marrow (BM) CD133(+)cells in patients with refractory angina. METHODS AND RESULTS: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent CCS II-IV angina despite optimal medical therapy, ≥ one myocardial segment with inducible ischemia in Tc-99m SPECT who underwent BM biopsy and were allocated to cells (n=16) or placebo (n=15)...
November 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27903567/increased-plasma-ige-accelerate-atherosclerosis-in-secreted-igm-deficiency
#19
Dimitrios Tsiantoulas, Ilze Bot, Maria Ozsvar Kozma, Laura Goederle, Thomas Perkmann, Karsten Hartvigsen, Daniel H Conrad, Johan Kuiper, Ziad Mallat, Christoph J Binder
RATIONALE: Deficiency of secreted IgM (sIgM(-/-)) accelerates atherosclerosis in Ldlr(-/-) mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized LDL and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown. OBJECTIVE: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice...
November 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27899403/meta-analysis-of-genome-wide-association-studies-for-abdominal-aortic-aneurysm-identifies-four-new-disease-specific-risk-loci
#20
Gregory T Jones, Gerard Tromp, Helena Kuivaniemi, Solveig Gretarsdottir, Annette F Baas, Betti Giusti, Ewa Strauss, Femke N van 't Hof, Thomas Webb, Robert Erdman, Marylyn D Ritchie, James R Elmore, Anurag Verma, Sarah Pendergrass, Iftikhar J Kullo, Zi Ye, Peggy L Peissig, Omri Gottesman, Shefali S Verma, Jennifer Malinowski, Laura J Rasmussen-Torvik, Kenneth Borthwick, Diane T Smelser, David R Crosslin, Mariza de Andrade, Evan J Ryer, Catherine A McCarty, Erwin P Bottinger, Jennifer A Pacheco, Dana C Crawford, David S Carrell, Glenn S Gerhard, David P Franklin, David J Carey, Victoria L Phillips, Michael J Williams, Wenhua Wei, Ross Blair, Andrew A Hill, Thodur M Vasudevan, David R Lewis, Ian A Thomson, Jo Krysa, Geraldine B Hill, Justin Roake, Tony R Merriman, Grzegorz Oszkinis, Silvia Galora, Claudia Saracini, Rosanna Abbate, Raffaele Pulli, Carlo Pratesi, Athanasios Saratzis, Anna Verissimo, Suzannah J Bumpstead, Stephen A Badger, Rachel E Clough, Gillian W Cockerill, Hany Hafez, D J Scott, T S Futers, Simon P Romaine, Katherine Bridge, Kathryn J Griffin, Marc A Bailey, Alberto Smith, Matt M Thompson, Frank van Bockxmeer, Stefan E Matthiasson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jan D Blankensteijn, Joep A Teijink, Cisca Wijmenga, Jacqueline de Graaf, Lambertus A Kiemeney, Jes S Lindholt, Anne E Hughes, Declan T Bradley, Kathleen Stirrups, Jonathan Golledge, Paul E Norman, Janet T Powell, Steve E Humphries, Stephen E Hamby, Alison H Goodall, Christopher P Nelson, Natzi Sakalihasan, Audrey Courtois, Robert E Ferrell, Per Eriksson, Lasse Folkersen, Anders Franco-Cereceda, John D Eicher, Andrew D Johnson, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Eric Schadt, Johan L Björkegren, Leonard Lipovich, Anne M Drolet, Eric Verhoeven, Clark J Zeebregts, Robert H Geelkerken, Marc R van Sambeek, Steven M van Sterkenburg, Jean-Paul P de Vries, Kari Stefansson, John R Thompson, Paul I de Bakker, Panos Deloukas, Robert D Sayers, Seamus Harrison, Andre M van Rij, Nilesh J Samani, Matthew J Bown
RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). METHODS AND RESULTS: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32...
November 29, 2016: Circulation Research
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