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Circulation Research

David T Paik, Lei Tian, Jaecheol Lee, Nazish Sayed, Ian Y Chen, Siyeon Rhee, June-Wha Rhee, Youngkyun Kim, Robert C Wirka, Jan W Buikema, Sean M Wu, Kristy Red-Horse, Thomas Quertermous, Joseph C Wu
<u>Rationale:</u> Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have risen as a useful tool in cardiovascular research, offering a wide gamut of translational and clinical applications. However, inefficiency of the currently available iPSC-EC differentiation protocol and underlying heterogeneity of derived iPSC-ECs remain as major limitations of iPSC-EC technology. <u>Objective:</u> Here we performed droplet-based single-cell RNA-sequencing (scRNA-seq) of the human iPSCs following iPSC-EC differentiation...
July 9, 2018: Circulation Research
Katrien Vandoorne, David Rohde, Hye-Yeong Kim, Gabriel Courties, Gregory R Wojtkiewicz, Lisa Honold, Friedrich F Hoyer, Vanessa Frodermann, Ribhu Nayar, Fanny E Herisson, Yookyung Jung, Pauline Désogère, Claudio Vinegoni, Peter Caravan, Ralph Weissleder, David E Sosnovik, Charles P Lin, Filip K Swirski, Matthias Nahrendorf
<u>Rationale:</u> Inflammatory stress induced by exposure to bacterial lipopolysaccharide (LPS) causes hematopoietic stem cell (HSC) expansion in the bone marrow niche, generating a cellular immune response. As an integral component of the hematopoietic stem cell niche, the bone marrow vasculature regulates the production and release of blood leukocytes, which protect the host against infection but also fuel inflammatory diseases. <u>Objective:</u> We aimed to develop imaging tools to explore vascular changes in the bone marrow niche during acute inflammation...
July 6, 2018: Circulation Research
Shirin Issa Bhaloo, Yifan Wu, Alexandra LE Bras, Baoqi Yu, Wenduo Gu, Yao Xie, Jiacheng Deng, Zhihong Wang, Zhongyi Zhang, Deling Kong, Yanhua Hu, Aijuan Qu, Qiang Zhao, Qingbo Xu
<u>Rationale:</u> Vascular progenitor cells (VPCs) play key roles in physiological and pathological vascular remodelling, a process that is crucial for the regeneration of acellular biodegradable scaffolds engineered as vital strategies against the limited availability of healthy autologous vessels for bypass grafting. Therefore, understanding the mechanisms driving VPCs recruitment and differentiation could help the development of new strategies to improve Tissue-Engineered Vessel Grafts (TEVGs) and design drug-targeted therapy for vessel regeneration...
July 6, 2018: Circulation Research
Mary N Woessner, Mitch D VanBruggen, Carl F Pieper, Richard Sloane, William E Kraus, Andrew J Gow, Jason D Allen
<u>Rationale:</u> A primary goal of therapy for patients with peripheral arterial disease and intermittent claudication (PAD+IC) is increased ambulatory function. Supervised exercise rehabilitation was recently shown to confer superior walking benefits to pharmacological or surgical interventions. Increases in plasma inorganic nitrite, via oral nitrate, have been shown to increase exercise performance in both human and animal models, especially in hypoxic conditions. <u>Objective:</u> To determine whether a 36-session exercise rehabilitation program while consuming oral inorganic nitrate (4...
July 5, 2018: Circulation Research
Ryu Watanabe, Toshihisa Maeda, Hui Zhang, Gerald J Berry, Markus Zeisbrich, Robert D Brockett, Andrew E Greenstein, Lu Tian, Jörg Goronzy, Cornelia M Weyand
<u>Rationale:</u> Giant cell arteritis (GCA), a primary vasculitis of medium and large arteries, is associated with vessel wall damage, elastic membrane fragmentation and vascular remodeling. Proteinases are believed to contribute to pathogenesis by degrading extracellular matrix and causing tissue injury. <u>Objective:</u> The matrix metalloproteinase 9 (MMP-9), a type IV collagenase, is produced in the vasculitic lesions of GCA. It is unknown which pathogenic processes are MMP-9 dependent...
July 3, 2018: Circulation Research
Mengcheng Shen, Mei Hu, Paul W Fedak, Gavin Y Oudit, Zamaneh Kassiri
<u>Rationale:</u> Disintegrin and metalloproteinase-17 (ADAM17) is a membrane-bound enzyme that regulates bioavailability of multiple transmembrane proteins by proteolytic processing. ADAM17 has been linked to a number of pathologies, but its role in thoracic aortic aneurysm (TAA) has not been determined. <u>Objective:</u> To explore the cell-specific functions of vascular ADAM17 in the pathogenesis and progression of TAA. <u>Methods and Results:</u> In aneurysmal thoracic aorta from patients, ADAM17 was increased in tunica media and intima...
June 21, 2018: Circulation Research
Ayman S Samman-Tahhan, Muhammad Hammadah, Heval M Kelli, Jeong Hwan Kim, Pratik B Sandesara, Ayman Alkhoder, Belal Kaseer, Mohamad M Gafeer, Matthew L Topel, Salim S Hayek, Wesley T O'Neal, Malik Obideen, Yi-An Ko, Chang Liu, Iraj Hesaroieh, Ernestine A Mahar, Viola Vaccarino, Edmund K Waller, Arshed A Quyyumi
<u>Rationale:</u> Blacks compared to Whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes, however, little is known about racial differences in CPCs. <u>Objective:</u> To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction (AMI) and the predictive value of CPC counts in Blacks compared with Whites...
June 21, 2018: Circulation Research
Carolin Rommel, Stephan Rösner, Achim Lother, Margareta Barg, Martin Schwaderer, Ralf Gilsbach, Timo Bömicke, Tilman Schnick, Sandra Mayer, Sophia Doll, Michael Hesse, Oliver Kretz, Brigitte Stiller, Franz-Josef Neumann, Matthias Mann, Markus Krane, Bernd K Fleischmann, Ursula Ravens, Lutz Hein
<u>Rationale:</u> Structural and electrophysiological remodeling of the atria are recognized consequences of sustained atrial arrhythmias, such as atrial fibrillation (AF). The identification of underlying key molecules and signaling pathways has been challenging due to the changing cell type composition during structural remodeling of the atria. <u>Objective:</u> Thus, the aims of our study were (1) to search for transcription factors and downstream target genes, which are involved in atrial structural remodeling, (2) to characterize the significance of the transcription factor ETV1 in atrial remodeling and arrhythmia and (3) to identify ETV1-dependent gene regulatory networks in atrial cardiac myocytes...
June 21, 2018: Circulation Research
Changchen Xiao, Kan Wang, Yinchuan Xu, Hengxun Hu, Na Zhang, Yingchao Wang, Zhiwei Zhong, Jing Zhao, Qingju Li, Dan Zhu, Changle Ke, Shuhan Zhong, Xianpeng Wu, Hong Yu, Wei Zhu, Jinghai Chen, Jianyi Zhang, Jian'an Wang, Xinyang Hu
<u>Rationale:</u> Autophagy can preserve cell viability under conditions of mild ischemic stress by degrading damaged organelles for ATP production, but under conditions of severe ischemia, it can promote cell death and worsen cardiac performance. Mesenchymal stem cells (MSCs) are cardioprotective when tested in animal models of myocardial infarction (MI), but whether these benefits occur through the regulation of autophagy is unknown. <u>Objective:</u> To determine whether transplanted MSCs reduce the rate of autophagic degradation (autophagic flux) in infarcted hearts and if so, to characterize the mechanisms involved...
June 19, 2018: Circulation Research
Francisco Fernández-Avilés, Ricardo Sanz-Ruiz, Jan Bogaert, Ana Casado Plasencia, Inmaculada Gilaberte, Ann Belmans, María Eugenia Fernández-Santos, Dominique Charron, Miguel Mulet, Raquel Yotti, Itziar Palacios, Manuel Luque, Rafael Sádaba, J A San Roman, Mariano Larman, Pedro L Sánchez, Juan Sanchis, Manuel F Jimenez-Navarro, Piet Claus, Reem Al-Daccak, Eleuterio Lombardo, José Luis Abad, Olga Delarosa, Lucia Corcostegui, Javier Bermejo, Stefan Janssens
<u>Rationale:</u> Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory and regenerative properties with a robust safety profile in large animal models of heart disease. <u>Objective:</u> To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment elevation myocardial infarction (STEMI). <u>Methods and Results:</u> CAREMI was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with STEMI, LVEF ≤ 45% and infarct size ≥ 25% of left ventricular (LV) mass by cardiac magnetic resonance (MR), who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at day 5-7...
June 19, 2018: Circulation Research
Cornelis J Boogerd, Xiaoming Zhu, Ivy Aneas, Noboru J Sakabe, Lunfeng Zhang, Debora R Sobreira, Lindsey E Montefiori, Julius Bogomolovas, Amelia C Joslin, Bin Zhou, Ju Chen, Marcelo Nobrega, Sylvia M Evans
<u>Rationale:</u> Mutations in the transcription factor TBX20 are associated with congenital heart disease. Germline ablation of Tbx20 results in abnormal heart development and embryonic lethality by E9.5. As Tbx20 is expressed in multiple cell lineages required for myocardial development, including pharyngeal endoderm, cardiogenic mesoderm, endocardium, and myocardium, the cell type specific requirement for Tbx20 in early myocardial development remains to be explored. <u>Objective:</u> Here, we investigated roles of Tbx20 in mid-gestation cardiomyocytes for heart development...
June 14, 2018: Circulation Research
Swati Dey, Deeptankar DeMazumder, Agnieszka Sidor, D Brian Foster, Brian O'Rourke
RATIONALE: Despite increasing prevalence and incidence of heart failure (HF), therapeutic options remain limited. In early stages of HF, sudden cardiac death (SCD) from ventricular arrhythmias claims many lives. Reactive oxygen species (ROS) have been implicated in both arrhythmias and contractile dysfunction. However, little is known about how ROS in specific subcellular compartments contribute to HF or SCD pathophysiology. The role of ROS in chronic proteome remodeling has not been explored...
July 20, 2018: Circulation Research
Bojan Vrtovec, Gregor Poglajen, Matjaz Sever, Gregor Zemljic, Sabina Frljak, Andraz Cerar, Marko Cukjati, Martina Jaklic, Peter Cernelc, Francois Haddad, Joseph C Wu
<u>Rationale:</u> Preclinical data in heart failure models suggest that repetitive stem cell therapy may be superior to single-dose cell administration. <u>Objective:</u> We investigated whether repetitive administration of CD34+ cells is superior to single dose administration in patients with non-ischemic dilated cardiomyopathy (DCM). <u>Methods and Results:</u> Of 66 patients with DCM, NYHA functional class III, and left ventricular ejection fraction (LVEF)< 40% enrolled in the study, 60 were randomly allocated to repetitive cell therapy (Group A, N=30), or single cell therapy (Group B, N=30)...
June 7, 2018: Circulation Research
Anna-Eliane Hopf, Christian Andresen, Sebastian Kötter, Malgorzata Isic, Kamila Ulrich, Senem Sahin, Sabine Bongardt, Wilhelm Roell, Felicitas Drove, Nina Scheerer, Leni Vandekerckhove, Gilles W De Keulenaer, Nazha Hamdani, Wolfgang A Linke, Martina Krüger
<u>Rationale:</u> Increased titin-dependent cardiomyocyte tension is a hallmark of heart failure with preserved ejection fraction (HFpEF) associated with type-2 diabetes mellitus (T2DM). However, the insulin-related signaling pathways that modify titin-based cardiomyocyte tension, thereby contributing to modulation of diastolic function, are largely unknown. <u>Objective:</u> We aimed to determine how impaired insulin signaling affects titin expression and phosphorylation and thus increases passive cardiomyocyte tension, and whether metformin or neuregulin-1 can correct disturbed titin modifications and increased titin-based stiffness...
May 14, 2018: Circulation Research
Soichi Sano, Kousei Ohshima, Ying Wang, Yasufumi Katanasaka, Miho Sano, Kenneth Walsh
<u>Rationale:</u> Clonal hematopoiesis has been associated with increased mortality and cardiovascular disease (CVD). This condition can arise from somatic mutations in pre-leukemic driver genes within hematopoietic stem/progenitor cells (HSPC). Approximately 40 candidate driver genes have been identified, but mutations in only one of these genes, Ten-Eleven Translocation-2 (TET2), has been shown to casually contribute to CVD in murine models. <u>Objective:</u> To develop a facile system to evaluate the disease characteristics of different clonal hematopoiesis driver genes using lentivirus vector and CRISPR/Cas9 methodology...
May 4, 2018: Circulation Research
Mariann Gyöngyösi, Paul M Haller, Derek J Blake, Enca Martin Rendon
Heart failure (HF) is one of the leading causes of death worldwide and has reached epidemic proportions in most industrialized nations. Despite major improvements in the treatment and management of the disease, the prognosis for patients with HF remains poor with approximately only half of patients surviving for 5 years or longer after diagnosis. The poor prognosis of HF patients is in part because of irreparable damage to cardiac tissue and concomitant maladaptive changes associated with the disease. Cell-based therapies may have the potential to transform the treatment and prognosis of HF through regeneration or repair of damaged cardiac tissue...
July 6, 2018: Circulation Research
Gregory J Bittle, David Morales, Kristopher B Deatrick, Nathaniel Parchment, Progyaparamita Saha, Rachana Mishra, Sudhish Sharma, Nicholas Pietris, Alexander Vasilenko, Casey Bor, Chetan Ambastha, Muthukumar Gunasekaran, Deqiang Li, Sunjay Kaushal
Hypoplastic left heart syndrome is a type of congenital heart disease characterized by underdevelopment of the left ventricle, outflow tract, and aorta. The condition is fatal if aggressive palliative operations are not undertaken, but even after the complete 3-staged surgical palliation, there is significant morbidity because of progressive and ultimately intractable right ventricular failure. For this reason, there is interest in developing novel therapies for the management of right ventricular dysfunction in patients with hypoplastic left heart syndrome...
July 6, 2018: Circulation Research
Monisha N Banerjee, Roberto Bolli, Joshua M Hare
Given the rising prevalence of cardiovascular disease worldwide and the limited therapeutic options for severe heart failure, novel technologies that harness the regenerative capacity of the heart are sorely needed. The therapeutic use of stem cells has the potential to reverse myocardial injury and improve cardiac function, in contrast to most current medical therapies that only mitigate heart failure symptoms. Nearly 2 decades and >200 trials for cardiovascular disease have revealed that most cell types are safe; however, their efficacy remains controversial, limiting the transition of this therapy from investigation to practice...
July 6, 2018: Circulation Research
Jianyi Zhang, Wuqiang Zhu, Milica Radisic, Gordana Vunjak-Novakovic
Some of the most significant leaps in the history of modern civilization-the development of article in China, the steam engine, which led to the European industrial revolution, and the era of computers-have occurred when science converged with engineering. Recently, the convergence of human pluripotent stem cell technology with biomaterials and bioengineering have launched a new medical innovation: functional human engineered tissue, which promises to revolutionize the treatment of failing organs including most critically, the heart...
July 6, 2018: Circulation Research
Priyanka Garg, Vivek Garg, Rajani Shrestha, Michael C Sanguinetti, Timothy J Kamp, Joseph C Wu
Life threatening ventricular arrhythmias leading to sudden cardiac death are a major cause of morbidity and mortality. In the absence of structural heart disease, these arrhythmias, especially in the younger population, are often an outcome of genetic defects in specialized membrane proteins called ion channels. In the heart, exceptionally well-orchestrated activity of a diversity of ion channels mediates the cardiac action potential. Alterations in either the function or expression of these channels can disrupt the configuration of the action potential, leading to abnormal electrical activity of the heart that can sometimes initiate an arrhythmia...
July 6, 2018: Circulation Research
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