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Circulation Research

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https://www.readbyqxmd.com/read/29326144/a-new-secretory-peptide-of-natriuretic-peptide-family-osteocrin-suppresses-the-progression-of-congestive-heart-failure-after-myocardial-infarction
#1
Takahiro Miyazaki, Kentaro Otani, Ayano Chiba, Hirohito Nishimura, Takeshi Tokudome, Haruko Watanabe-Takano, Ayaka Matsuo, Hiroyuki Ishikawa, Keiko Shimamoto, Hajime Fukui, Yugo Kanai, Akihiro Yasoda, Soshiro Ogata, Kunihiro Nishimura, Naoto Minamino, Naoki Mochizuki
Rationale: An increase of severe ischemic heart diseases results in an increase of the patients with congestive heart failure (CHF). Therefore, new therapies are expected in addition to recanalization of coronary arteries. Previous clinical trials using natriuretic peptides (NPs) prove the improvement of CHF by NPs. Objective: We aimed at investigating whether osteocrin (OSTN) peptide potentially functioning as an NP clearance receptor (NPR3)-blocking peptide can be used as a new therapeutic peptide for treating CHF after myocardial infarction (MI) using animal models...
January 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29321129/novel-reversible-model-of-atherosclerosis-and-regression-using-oligonucleotide-regulation-of-the-ldl-receptor
#2
Debapriya Basu, Yunying Hu, Lesley-Ann Huggins, Adam E Mullick, Mark J Graham, Tomasz A Wietecha, Shelley L Barnhart, Allison Mogul, Katharina Pfeiffer, Andreas Zirlik, Edward A Fisher, Karin E Bornfeldt, Florian Willecke, Ira J Goldberg
Rationale: Animal models have been used to explore factors that regulate atherosclerosis. More recently, they have been used to study the factors that promote loss of macrophages and reduction in lesion size after lowering of plasma cholesterol levels. However, current animal models of atherosclerosis regression require challenging surgeries, time-consuming breeding strategies, and/or methods that block liver lipoprotein secretion. Objective: We sought to develop a more direct and time-effective method to create and then reverse hypercholesterolemia as well as atherosclerosis via transient knockdown of the hepatic LDL receptor (LDLR) followed by its rapid restoration...
January 10, 2018: Circulation Research
https://www.readbyqxmd.com/read/29317431/suppression-of-activated-foxo-transcription-factors-in-the-heart-prolongs-survival-in-a-mouse-model-of-laminopathies
#3
Gaelle Auguste, Priyatansh Gurha, Raffaella Lombardi, Cristian Coarfa, James T Willerson, Ali J Marian
Rationale: Mutations in the LMNA gene, encoding nuclear inner membrane protein Lamin A/C, cause distinct phenotypes, collectively referred to as laminopathies. Heart failure, conduction defects, and arrhythmias are the common causes of death in laminopathies. Objective: To identify and therapeutically target the responsible mechanism(s) for cardiac phenotype in laminopathies. Methods and Results: Whole heart RNA sequencing was performed prior to the onset of cardiac dysfunction in the Lmna-/- and matched control mice...
January 9, 2018: Circulation Research
https://www.readbyqxmd.com/read/29301854/autophagy-is-required-for-sortilin-mediated-degradation-of-apolipoprotein-b100
#4
Jaume Amengual, Liang Guo, Alanna Strong, Julio Madrigal-Matute, Haizhen Wang, Susmita Kaushik, Jeffrey L Brodsky, Daniel J Rader, Ana Maria Cuervo, Edward A Fisher
Rationale: Genome-Wide Association Studies identified single nucleotide polymorphisms (SNPs) near the SORT1 locus strongly associated with decreased plasma low-density lipoprotein cholesterol (LDL-C) levels and protection from atherosclerotic cardiovascular disease and myocardial infarction. The minor allele of the causal SORT1 SNP locus creates a putative C/EBPα binding site in the SORT1 promoter, thereby increasing sortilin expression by 12-fold in liver, which is rich in this transcription factor. Our previous studies in mice have showed reductions in plasma LDL-C and its principal protein component, apolipoprotein B (apoB) with increased SORT1 expression, and in vitro studies suggested that sortilin promoted the presecretory lysosomal degradation of apoB associated with the LDL precursor, very-low density lipoprotein (VLDL)...
January 4, 2018: Circulation Research
https://www.readbyqxmd.com/read/29301853/-pro-renin-receptor-inhibition-reprograms-hepatic-lipid-metabolism-and-protects-mice-from-diet-induced-obesity-and-hepatosteatosis
#5
Liwei Ren, Yuan Sun, Hong Lu, Dien Ye, Lijuan Han, Na Wang, Alan Daugherty, Furong Li, Miaomiao Wang, Fengting Su, Wenjun Tao, Jie Sun, Noam Zelcer, Adam E Mullick, Ah J Danser, Yizhou Jiang, Yongcheng He, Xiongzhong Ruan, Xifeng Lu
Rationale: An elevated level of plasma low-density lipoprotein (LDL) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDL receptor (LDLR) and SORT1, independently of the renin-angiotensin system. Objective: To investigate the physiological role of [P]RR in lipid metabolism in vivo. Methods and Results: We used N-Acetylgalactosamine (GalNAc) modified antisense oligonucleotides (ASO) to specifically inhibit hepatic [P]RR expression in C57BL/6J mice, and studied the consequences this has on lipid metabolism...
January 4, 2018: Circulation Research
https://www.readbyqxmd.com/read/29298775/yes-associated-protein-promotes-angiogenesis-via-signal-transducer-and-activator-of-transcription-3-in-endothelial-cells
#6
Jinlong He, Qiankun Bao, Yan Zhang, Mingming Liu, Huizhen Lv, Yajin Liu, Liu Yao, Bochuan Li, Chenghu Zhang, Shuang He, Guijin Zhai, Yan Zhu, Xin Liu, Kai Zhang, Xiujie Wang, Ming-Hui Zou, Yi Zhu, Ding Ai
Rationale: Angiogenesis is a complex process regulating endothelial cell (EC) functions. Emerging lines of evidence support that Yes-associated protein (YAP) plays an important role in regulating the angiogenic activity of ECs. Objective: To specify the effect of EC YAP on angiogenesis and its underlying mechanisms. Methods and Results: In ECs, vascular endothelial growth factor reduced YAP phosphorylation time- and dose-dependently and increased its nuclear accumulation. Using Tie2Cre-mediated YAP transgenic (Tie2Cre-YAPTg) mice, we found that YAP promoted angiogenesis in the postnatal retina and tumor tissues...
January 3, 2018: Circulation Research
https://www.readbyqxmd.com/read/29298774/kidney-transplantation-in-a-patient-lacking-cytosolic-phospholipase-a2-proves-renal-origins-of-urinary-pgi-m-and-tx-m
#7
Jane Mitchell, Rebecca B Knowles, Nicholas S Kirkby, Daniel M Reed, Matthew L Edin, William E White, Melissa V Chan, Hilary Longhurst, Magdi Yaqoob, Ginger L Milne, Darryl C Zeldin, Timothy D Warner
Rationale: The balance between vascular prostacyclin which is anti-thrombotic and platelet thromboxane A2 which is pro-thrombotic is fundamental to cardiovascular health. Prostacyclin and thromboxane A2 are formed following the concerted actions of cytosolic phospholipase A2 (cPLA2α) and cyclooxygenase. Urinary 2,3-dinor-6-keto PGF1α (PGI-M) and 11-dehydro-TXB2 (TX-M) have been taken as biomarkers of prostacyclin and thromboxane A2 formation with the circulation and used to explain cyclooxygenase biology and patient phenotypes, despite concerns that urinary PGI-M and TX-M originate in the kidney...
January 3, 2018: Circulation Research
https://www.readbyqxmd.com/read/29284691/a-to-i-editing-of-microrna-487b-alters-target-gene-selection-after-ischemia-and-promotes-neovascularization
#8
Reginald V van der Kwast, Eva van Ingen, Laura Parma, Hendrika A Peters, Paul H Quax, A Y Nossent
Rationale: Adenosine-to-inosine (A-to-I) editing of microRNAs has the potential to cause a shift in target-site selection. 2'-O-ribose-methylation (2'OMe) of adenosine residues however, has been shown to inhibit A-to-I-editing. Objective: To investigate whether angiomiR miR487b is subject to A-to-I-editing and/or 2'OMe during neovascularization. Methods and Results: cDNA was prepared from C57BL/6-mice subjected to hindlimb ischemia. Using Sanger-sequencing and endonuclease digestion, we identified and validated A-to-I-editing of the miR487b seed-sequence...
December 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/29284690/ampk%C3%AE-2-protects-against-the-development-of-heart-failure-by-enhancing-mitophagy-via-pink1-phosphorylation
#9
Bei Wang, Jiali Nie, Lujin Wu, Yangyang Hu, Zeng Wen, Lingli Dong, Ming-Hui Zou, Chen Chen, Dao Wen Wang
Rationale: Mitochondrial dysfunction plays an important role in heart failure (HF). However, the molecular mechanisms regulating mitochondrial functions via selective mitochondrial autophagy (mitophagy) are poorly understood. Objective: We sought to determine the role of AMP-activated protein kinase (AMPK) in selective mitophagy during HF. Methods and Results: An isoform shift from AMPKα2 to AMPKα1 was observed in failing-heart samples from HF patients and transverse aortic constriction (TAC)-induced mice, accompanied by decreased mitophagy and mitochondrial function...
December 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/29282212/musclemotion-a-versatile-open-software-tool-to-quantify-cardiomyocyte-and-cardiac-muscle-contraction-in-vitro-and-in-vivo
#10
Luca Sala, Berend J van Meer, Leon T Tertoolen, Jeroen Bakkers, Milena Bellin, Richard P Davis, Chris N Denning, Michel A Dieben, Thomas Eschenhagen, Elisa Giacomelli, Catarina Grandela, Arne Hansen, Eduard Holman, Monique R Jongbloed, Sarah M Kamel, Charlotte D Koopman, Quentin Lachaud, Ingra Mannhardt, Mervyn P Mol, Diogo Mosqueira, Valeria V Orlova, Robert Passier, Marcelo C Ribeiro, Umber Saleem, Godfrey Smith, Francis L L Burton, Christine L Mummery
Rationale: There are several methods to measure cardiomyocyte (CM) and muscle contraction but these require customized hardware, expensive apparatus and advanced informatics or can only be used in single experimental models. Consequently, data and techniques have been difficult to reproduce across models and laboratories, analysis is time consuming and only specialist researchers can quantify data. Objective: Here we describe and validate an automated, open source software tool (MUSCLEMOTION) adaptable for use with standard laboratory- and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes and pharmacological responses...
December 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/29282211/late-ca2-sparks-and-ripples-during-the-systolic-ca2-transient-in-heart-muscle-cells
#11
Ewan D Fowler, Cherrie H Kong, Jules Hancox, Mark B Cannell
Rationale: The development of a refractory period for Ca2+ spark initiation after Ca2+ release in cardiac myocytes, should inhibit further Ca2+ release during the action potential (AP) plateau. However, Ca2+ release sites that did not initially activate, or which have prematurely recovered from refractoriness might release Ca2+ later during the AP and alter the cell-wide Ca2+ transient. Objective: To investigate the possibility of late Ca2+ spark (LCS) activity in intact isolated cardiac myocytes using fast confocal line scanning with improved confocality and signal to noise...
December 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/29279301/inositol-polyphosphate-multikinase-inhibits-angiogenesis-via-inositol-pentakisphosphate-induced-hif-1%C3%AE-degradation
#12
Chenglai Fu, Richa Tyagi, Alfred C Chin, Tomas Rojas, Ruo-Jing Li, Prasun Guha, Isaac A Bernstein, Feng Rao, Risheng Xu, Jiyoung Y Cha, Jing Xu, Adele M Snowman, Gregg L Semenza, Solomon H Snyder
Rationale: Inositol polyphosphate multikinase (IPMK) and its major product inositol pentakisphosphate (IP5) regulate a variety of cellular functions, but their role in vascular biology remains unexplored. Objective: We have investigated the role of IPMK in regulating angiogenesis. Methods and Results: Deletion of IPMK in fibroblasts induces angiogenesis in both in vitro and in vivo models. IPMK deletion elicits a substantial increase of vascular endothelial growth factor (VEGF), which mediates the regulation of angiogenesis by IPMK...
December 26, 2017: Circulation Research
https://www.readbyqxmd.com/read/29273600/deficiency-of-natriuretic-peptide-receptor-2-promotes-bicuspid-aortic-valves-aortic-valve-disease-left-ventricular-dysfunction-and-ascending-aortic-dilatations-in-mice
#13
Mark C Blaser, Kuiru Wei, Rachel L Adams, Yu-Qing Zhou, Laura-Lee Caruso, Zahra Mirzaei, Alan Lam, Richard K Tam, Hangjun Zhang, Scott P Heximer, Mark Henkelman, Craig A Simmons
Rationale: Aortic valve disease is a cell-mediated process without effective pharmacotherapy. C-type natriuretic peptide (CNP) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells (VICs), and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve health in vivo. Objective: To determine whether a deficient CNP signaling axis in mice causes accelerated progression of aortic valve disease. Methods and Results: In cultured porcine VICs, CNP inhibited pathological differentiation via the guanylate cyclase natriuretic peptide receptor 2 (NPR2) and not the G-protein-coupled clearance receptor NPR3...
December 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/29269349/infarct-fibroblasts-do-not-derive-from-bone-marrow-lineages
#14
Thomas Moore-Morris, Paola Cattaneo, Nuno Guimarães-Camboa, Julius Bogomolovas, Marta Cedenilla, Indroneal Banerjee, Mercedes Ricote, Tatiana Kisseleva, Lunfeng Zhang, Yusu Gu, Nancy D Dalton, Kirk L Peterson, Ju Chen, Michel Puceat, Sylvia M Evans
Rationale: Myocardial infarction (MI) is a major cause of adult mortality worldwide. The origin(s) of cardiac fibroblasts that constitute the post-infarct scar remain controversial, in particular the potential contribution of bone marrow lineages to activated fibroblasts within the scar. Objective: To establish the origin(s) of infarct fibroblasts using lineage tracing and bone marrow transplants, and a robust marker for cardiac fibroblasts, the Collagen1a1-GFP reporter. Methods and Results: Using genetic lineage tracing or bone marrow transplant, we found no evidence for Collagen-producing fibroblasts derived from hematopoietic or bone marrow lineages in hearts subjected to permanent left anterior descending (LAD) coronary artery ligation...
December 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/29242238/short-leukocyte-telomere-length-precedes-clinical-expression-of-atherosclerosis-blood-and-muscle-model
#15
Athanase Benetos, Simon Toupance, Sylvie Gautier, Carlos Labat, Masayuki Kimura, Pascal M Rossi, Nicla Settembre, Jacques Hubert, Luc Frimat, Baptiste Bertrand, Mourad Boufi, Xavier Flecher, Nicolas Sadoul, Pascal Eschwege, Michà le Kessler, Irene P Tzanetakou, Ilias P Doulamis, Panagiotis S Konstantopoulos, Aspasia I Tzani, Laskarina-Maria Korou, Anastasios Gkogkos, Konstantinos G Perreas, Evangelos Menenakos, George Samanidis, Michail Vasiloglou-Gkanis, Jeremy D Kark, Sergueï Malikov, Simon Verhulst, Abraham Aviv
Rationale:  Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth and/or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, while TL in skeletal muscle (M) represents a minimally replicative tissue. Objective: We measured LTL and MTL in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD...
December 14, 2017: Circulation Research
https://www.readbyqxmd.com/read/29237722/pannexin-1-channels-as-an-unexpected-new-target-of-the-anti-hypertensive-drug-spironolactone
#16
Miranda E Good, Yu-Hsin Chiu, Ivan K Poon, Christopher B Medina, Joshua T Butcher, Suresh K Mendu, Leon J DeLalio, Alexander W Lohman, Norbert Leitinger, Eugene J Barrett, Ulrike M Lorenz, Bimal N Desai, Iris Z Jaffe, Douglas Bayliss, Brant E Isakson, Kodi S Ravichandran
Rationale: Resistant hypertension is a major health concern with unknown etiology. Spironolactone is an effective anti-hypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization (WHO) as an "essential" medication. Although spironolactone can act at the mineralocorticoid receptor (NR3C2), there is increasing evidence of mineralocorticoid receptor (MR)-independent effects of spironolactone. Objective: Here, we detail the unexpected discovery that pannexin 1 (Panx1) channels could be a relevant in vivo target of spironolactone...
December 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/29233846/ve-cadherin-mediated-epigenetic-regulation-of-endothelial-gene-expression
#17
Marco F Morini, Costanza Giampietro, Monica Corada, Federica Pisati, Elisa Lavarone, Sara I Cunha, Lei L Conze, Nicola J O'Reilly, Dhira Joshi, Svend Kjaer, Roger George, Emma Nye, Anqi Ma, Jian Jin, Richard Mitter, Michela Lupia, Ugo Cavallaro, Diego Pasini, Dinis P Calado, Elisabetta Dejana, Andrea Taddei
Rationale: The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumours, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular inter-endothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, vascular endothelial (VE)-cadherin (VEC), upregulate genes with key roles in endothelial differentiation and stability...
December 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/29233845/physiologic-mitochondrial-fragmentation-is-a-normal-cardiac-adaptation-to-increased-energy-demand
#18
Michael Coronado, Giovanni Fajardo, Kim Nguyen, Mingming Zhao, Kristina B Kooiker, Gwanghyun Jung, Dong-Qing Hu, Sushma Reddy, Erik Sandoval, Aleksandr Stotland, Roberta A Gottlieb, Daniel Bernstein
Rationale: Mitochondria play a dual role in the heart, responsible for meeting energetic demands and regulating cell death. Paradigms have held that mitochondrial fission and fragmentation are the result of pathologic stresses such as ischemia, are an indicator of poor mitochondrial health, and lead to mitophagy and cell death. However, recent studies demonstrate that inhibiting fission also results in decreased mitochondrial function and cardiac impairment, suggesting that fission is important for maintaining cardiac and mitochondrial bioenergetic homeostasis...
December 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/29212778/the-identification-of-64-novel-genetic-loci-provides-an-expanded-view-on-the-genetic-architecture-of-coronary-artery-disease
#19
Pim van der Harst, Niek Verweij
Rationale: Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. 97 genetic risk loci have been identified so far, but the identification of additional susceptibility loci might be important to enhance our understanding of the genetic architecture of CAD. Objective: To expand the number of genome-wide significant loci, catalog functional insights, and enhance our understanding of the genetic architecture of CAD. Methods and Results: We performed a genome-wide association study (GWAS) in 34,541 CAD cases and 261,984 controls of UK biobank Resource followed by replication in 88,192 cases and 162,544 controls from CARDIoGRAMplusC4D...
December 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/29208679/the-time-trial-effect-of-timing-of-stem-cell-delivery-following-st-elevation-myocardial-infarction-on-the-recovery-of-global-and-regional-left-ventricular-function-final-2-year-analysis
#20
Jay H Traverse, Timothy D Henry, Carl J Pepine, James T Willerson, Atul R Chugh, Phillip C Yang, David Zhao, Stephen G Ellis, John R Forder, Emerson C Perin, Marc S Penn, Antonis K Hatzopoulos, Jeffrey W Chambers, Kenneth Baran, Ganesh Raveendran, Adrian P Gee, Doris A Taylor, Lem Moyé, Ray F Ebert, Robert D Simari
Rationale: The TIME trial was the first cell therapy trial sufficiently powered to determine if timing of cell delivery following ST-elevation myocardial infarction (STEMI) affects recovery of left ventricular (LV) function. Objective: To report the 2-year clinical and cardiac magnetic resonance imaging (cMRI) results and their modification by microvascular obstruction (MVO). Methods and Results: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells (BMC) vs...
December 5, 2017: Circulation Research
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