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Circulation Research

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https://www.readbyqxmd.com/read/28209718/demethylation-of-h3k27-is-essential-for-the-induction-of-direct-cardiac-reprogramming-by-mir-combo
#1
Sophie Dal-Pra, Conrad P Hodgkinson, Maria Mirotsou, Imke Kirste, Victor J Dzau
Rationale: Direct reprogramming of cardiac fibroblasts to cardac omyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of four microRNAs (miR-1, miR-133, miR-208 and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown. Objective: Here we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism...
February 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28193608/dectin-2-deficiency-modulates-th1-differentiation-and-improves-wound-healing-after-myocardial-infarction
#2
Xiaoxiang Yan, Hang Zhang, Qin Fan, Jian Hu, Rong Tao, Qiujing Chen, Yoichiro Iwakura, Weifeng Shen, Lin Lu, Qi Zhang, Ruiyan Zhang
Rationale: Macrophages are involved in wound healing after myocardial infarction (MI). The role of Dectin-2, a pattern recognition receptor mainly expressed on myeloid cells, in the infarct healing remains unknown. Objective: To determine whether Dectin-2 signaling is involved in the healing process and cardiac remodeling after MI, and to elucidate the underlying molecular mechanisms. Methods and Results: In a mouse model of permanent coronary ligation, Dectin-2, mainly expressed in macrophages, was shown to be increased in the early phase after MI...
February 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/28179432/an-evolutionarily-conserved-role-for-polydom-svep1-during-lymphatic-vessel-formation
#3
Terhi Kärpanen, Yvonne Padberg, Serge A van de Pavert, Cathrin Dierkes, Nanami Morooka, Josi Peterson-Maduro, Glenn van de Hoek, Max Adrian, Naoki Mochizuki, Kiyotoshi Sekiguchi, Friedemann Kiefer, Dörte Schulte, Stefan Schulte-Merker
Rationale: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood. Objective: Here, we identify the secreted Polydom/Svep1 protein as essential for formation of the lymphatic vasculature. We analyzed mutants in mice and zebrafish to gain insight into the role of Polydom/Svep1 in the lymphangiogenic process. Methods and Results: Phenotypic analysis of zebrafish polydom/svep1 mutants showed a decrease in venous and lympho-venous sprouting, which leads to an increased number of intersegmental arteries...
February 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28179431/repeated-cell-therapy-a-paradigm-shift-whose-time-has-come
#4
Roberto Bolli
Although treatment with stem/progenitor cells is a promising approach to heart disease, enthusiasm for cell therapy has been dampened by the inconsistent, modest, borderline, or undetectable benefits reported in clinical trials (all of which have used one dose of cells). As a result, clinical translation has not occurred (no cell-based therapy is close to being approved for heart disease), and a rising tide of skepticism has bedeviled the field,leading some critics even to question whether clinical studies should continue...
February 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28179430/polydom-is-an-extracellular-matrix-protein-involved-in-lymphatic-vessel-remodeling
#5
Nanami Morooka, Sugiko Futaki, Ryoko Sato-Nishiuchi, Masafumi Nishino, Yuta Totani, Chisei Shimono, Itsuko Nakano, Hiroyuki Nakajima, Naoki Mochizuki, Kiyotoshi Sekiguchi
: Rationale: Lymphatic vasculature constitutes a second vascular system, essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly-branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown. Objective: Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin α9β1...
February 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28174322/4d-microvascular-analysis-reveals-that-regenerative-angiogenesis-in-ischemic-muscle-produces-a-flawed-microcirculation
#6
John-Michael Arpino, Zengxuan Nong, Fuyan Li, Hao Yin, Nour W Ghonaim, Stephanie Milkovich, Brittany Balint, Caroline O'Neil, Graham M Fraser, Daniel Goldman, Christopher G Ellis, J G Pickering
RATIONALE: Angiogenesis occurs following ischemic injury to skeletal muscle and enhancing this response has been a therapeutic goal. However, to appropriately deliver oxygen, a precisely organized and exquisitely responsive microcirculation must form. Whether these network attributes exist in a regenerated microcirculation is unknown and methodologies for answering this have been lacking. OBJECTIVE: To develop 4D methodologies for elucidating microarchitecture and function of the reconstructed microcirculation in skeletal muscle...
February 7, 2017: Circulation Research
https://www.readbyqxmd.com/read/28167653/orai1-activates-proliferation-of-lymphatic-endothelial-cells-in-response-to-laminar-flow-through-kr%C3%A3-ppel-like-factors-2-and-4
#7
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Mingu Hong, Sunju Lee, James Burford, Georgina Gyarmati, Janos Peti-Peterdi, Sonal Srikanth, Yousang Gwack, Chester J Koh, Evgenii Boriushkin, Anne Hamik, Alex K Wong, Young-Kwon Hong
RATIONALE: Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown. OBJECTIVE: We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation. METHODS AND RESULTS: Primary endothelial cells from dermal blood and lymphatic vessels (BECs and LECs) were exposed to low-rate steady laminar flow...
February 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28137917/elevating-cxcr7-improves-angiogenic-function-of-epcs-via-akt-gsk-3%C3%AE-fyn-mediated-nrf2-activation-in-diabetic-limb-ischemia
#8
Xiaozhen Dai, Xiaoqing Yan, Jun Zeng, Jing Chen, Yuehui Wang, Jun Chen, Yan Li, Michelle T Barati, Kupper A Wintergerst, Kejian Pan, Matthew A Nystoriak, Daniel J Conklin, Gregg Rokosh, Paul N Epstein, Xiaokun Li, Yi Tan
RATIONALE: Endothelial progenitor cells (EPCs) respond to SDF-1 through receptors CXCR7 and CXCR4. Whether SDF-1 receptors involves in diabetes induced EPCs dysfunction remains unknown. OBJECTIVE: To determine the role of SDF-1 receptors in diabetic EPCs dysfunction. METHODS AND RESULTS: CXCR7 expression, but not CXCR4 was reduced in EPCs from db/db mice, which coincided with impaired tube formation. Knockdown of CXCR7 impaired tube formation of EPCs from normal mice, while up-regulation of CXCR7 rescued angiogenic function of EPCs from db/db mice...
January 30, 2017: Circulation Research
https://www.readbyqxmd.com/read/28130294/transcellular-pathways-in-lymphatic-endothelial-cells-regulate-changes-in-solute-transport-by-fluid-stress
#9
Valentina Triacca, Esra Guc, Witold W Kilarski, Marco Pisano, Melody A Swartz
RATIONALE: The transport of interstitial fluid and solutes into lymphatic vessels is important for maintaining interstitial homeostasis and delivering antigens and soluble factors to the lymph node for immune surveillance. Transendothelial transport across lymphatic endothelial cells (LECs) is commonly considered to occur paracellularly, or between cell-cell junctions, and driven by local pressure and concentration gradients. However, emerging evidence suggests that LECs also play active roles in regulating interstitial solute balance and can scavenge and store antigens, raising the possibility that vesicular or transcellular pathways may be important in lymphatic solute transport...
January 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/28119423/lipid-droplet-biogenesis-and-function-in-the-endothelium
#10
Andrew Kuo, Monica Y Lee, William C Sessa
RATIONALE: Fatty acids (FA) are transported across the capillary endothelium to parenchymal tissues. However, it is not known how endothelial cells (EC) process a post-prandial surge of FA. OBJECTIVE: This study was designed to characterize lipid droplet (LD) formation and function in EC. METHODS AND RESULTS: LD form and degrade in EC in vivo after FA loading. In cultured EC, LD synthesis and turnover is dynamic and function to protect EC from lipotoxic stress and provide FA for metabolic needs...
January 24, 2017: Circulation Research
https://www.readbyqxmd.com/read/28115390/inhibition-of-klf5-myo9b-rhoa-pathway-mediated-podosome-formation-in-macrophages-ameliorates-abdominal-aortic-aneurysm
#11
Dong Ma, Bin Zheng, Toru Suzuki, Ruonan Zhang, Chunyang Jiang, Disi Bai, Weina Yin, Zhan Yang, Xinhua Zhang, Lianguo Hou, Hong Zhan, Jin-Kun Wen
RATIONALE: Abdominal aortic aneurysms (AAAs) are characterized by pathological remodeling of the aortic wall. Although both increased Krüppel-like factor 5 (KLF5) expression and macrophage infiltration have been implicated in vascular remodeling, the role of KLF5 in macrophage infiltration and AAA formation remains unclear. OBJECTIVE: To determine the role of KLF5 in AAA formation and macrophage infiltration into AAAs. METHODS AND RESULTS: KLF5 expression was significantly increased in human AAA tissues and in two mouse models of experimental AAA...
January 23, 2017: Circulation Research
https://www.readbyqxmd.com/read/28096195/the-multifunctional-mitochondrial-epac1-controls-myocardial-cell-death
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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