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Figure 7: Beneficial Effects of the Dual Action of Neurohumoral System in LCZ696 Treatment

Masanobu Ishii, Koichi Kaikita, Koji Sato, Daisuke Sueta, Koichiro Fujisue, Yuichiro Arima, Yu Oimatsu, Tatsuro Mitsuse, Yoshiro Onoue, Satoshi Araki, Megumi Yamamuro, Taishi Nakamura, Yasuhiro Izumiya, Eiichiro Yamamoto, Sunao Kojima, Shokei Kim-Mitsuyama, Hisao Ogawa & Kenichi Tsujita
Quantification of plasma (A) aldosterone and (B) cGMP levels by ELISA 3 days after MI. (C) The ratio of plasma aldosterone to plasma cGMP. n = 28 per group. In these box-and-whisker plots, lines within the boxes represent median values; the upper and lower lines of the boxes represent the 75th and 25th percentiles, respectively; and the upper and lower bars outside the boxes represent maximum and minimum values within 1.5 times the interquartile range...

Visual Abstract - Microtubule-Mediated Misregulation of Junctophilin-2 Underlies T-Tubule Disruptions and Calcium Mishandling in mdx Mice: 10.1016/j.jacbts.2016.02.002

Kurt W. Prins, Michelle L. Asp, Huiliang Zhang, Wang Wang & Joseph M. Metzger
• Decreased junctophilin-2 levels are associated with cardiac t-tubule derangements in mdx mice, the mouse model of Duchenne muscular dystrophy (DMD).
• Reduced junctophilin-2 protein levels correlate with increases in total microtubule content in mdx hearts.
• Colchicine-mediated microtubule depolymerization increases junctophilin-2 protein levels and improves localization patterns which, in turn, are associated with t-tubule reorganization and reduced calcium sparks.
• This study identifies microtubule-mediated misregulation of junctophilin-2 as a novel molecular mechanism in Duchenne cardiomyopathy.

Figure 3: Cytosolic Ca

Dimosthenis Giamouridis, Mei Hua Gao, N. Chin Lai, Zhen Tan, Young Chul Kim, Tracy Guo, Atsushi Miyanohara, W. Matthijs Blankesteijn, Erik Biessen & H. Kirk Hammond
Cytosolic Ca2+ transients were measured in cardiac myocytes isolated from mice 9.0 ± 0.2 weeks after IV delivery of AAV8.UCn2 or AAV8.UCn3 (both at 1.9x1013 gc/kg) or saline (control). (A) Representative Indo-1 Ca2+ transient recordings from cardiac myocytes from 1 heart in each group. (B) Mean peak Ca2+ transients from multiple cardiac myocytes from each group, showing increased peak Ca2+ transients in cardiac myocytes isolated form mice following UCn2 and UCn3 gene transfer. There was...

Figure 4: Basal and Critical Conduction Velocities

Lukas J. Motloch, Kiyotake Ishikawa, Chaoqin Xie, Jun Hu, Jaume Aguero, Kenneth M. Fish, Roger J. Hajjar & Fadi G. Akar
(A) Representative depolarization isochrone maps from Ctrl and MI/iAL preparations at baseline (normokalemia, pacing cycle length 1,000 ms). Comparison of basal conduction velocity (CVb) in the Ctrl, MI, and MI/iAL preparations (Ctrl: n = 11; MI: n = 9; and MI/iAL: n = 10). No significant differences in CVb were found between the MI or MI/iAL preparations compared with the Ctrl preparations. (B) Representative electrogram tracings recorded at a wide range of pacing rates in...

Figure 5: In Vivo Engraftment of NDNF Overexpressing Old hBM-MSCs Improved Cardiac Function After MI

Hui-Fang Song, Sheng He, Shu-Hong Li, Wen-Juan Yin, Jun Wu, Jian Guo, Zheng-Bo Shao, Xiao-Yan Zhai, Hui Gong, Li Lu, Fang Wei, Richard D. Weisel, Jun Xie & Ren-Ke Li
(A) Representative M-mode echocardiographic images taken 28 days after myocardial infarction (MI) in mice that received implantation of control medium (medium; n = 5), empty vector–transduced human dermal fibroblasts (fibro; n = 6), NDNF-transduced human dermal fibroblasts (fibro+NDNF; n = 6), empty vector–transduced old hBM-MSCs (old; n = 6), NDNF-transduced old hBM-MSCs (old+NDNF; n = 7), or untransduced young hBM-MSCs (young; n = 5) into the border region immediately following MI. (B) Fractional shortening was...

Figure 1: Mortality Is Reduced in Rad

Janet R. Manning, Lakshman Chelvarajan, Bryana M. Levitan, Catherine N. Withers, Prabhakara R. Nagareddy, Christopher M. Haggerty, Brandon K. Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A. Andres & Jonathan Satin
(A) Survival curve of wild-type (WT) and Rad−/− shows significantly fewer spontaneous deaths in Rad−/− mice. *p < 0.05, WT versus Rad−/− mice. N = 63 WT myocardial infarction (MI), 75 Rad−/− MI, 25 WT sham, and 33 Rad−/− sham mice at risk at day 0. After 50 days, there were 58 WT MI mice at risk, and at 100 days, there were 57 WT MI mice at risk; all other counts remained the same...

Figure 2: Titin Isoform Expression in Nonfailing Donor (Control) and AS Patient Hearts

Michael Gotzmann, Susanne Grabbe, Dominik Schöne, Marion Von Frieling-Salewsky, Cristobal G. Dos Remedios, Justus Strauch, Matthias Bechtel, Johannes W. Dietrich, Andrea Tannapfel, Andreas Mügge & Wolfgang A. Linke
(A) Representative loose gel (1.8% polyacrylamide/1% agarose) resolving the titin isoforms N2BA and N2B. (B and C) Summary of results of densitometric analysis of titin protein composition, demonstrated as N2BA/N2B isoform expression ratio. Shown are box plots (median [first quartile, third quartile]) with whiskers and individual data points (red circles). (B) Mann-Whitney U test revealed statistically significant differences between control hearts and all AS patients (p = 0.005). (C) Comparison was made between study patients’...

Figure 2: Effect of Apelin and Exercise on PVR

Lauren Brash, Gareth D. Barnes, Melanie J. Brewis, A. Colin Church, Simon J. Gibbs, Luke S.G.E. Howard, Geeshath Jayasekera, Martin K. Johnson, Neil McGlinchey, Joelle Onorato, Joanne Simpson, Colin Stirrat, Stephen Thomson, Geoffrey Watson, Martin R. Wilkins, Carrie Xu, David J. Welsh, David E. Newby & Andrew J. Peacock
Pulmonary vascular resistance during infusion of (Pyr1)apelin-13 or matched saline placebo in patients with pulmonary arterial hypertension while undergoing exercise protocol. A zero reflects resting measurements, raise reflects measurements taken with legs raised in ergometers pedals at rest, then further measurements at 20% and 40% of previous erect maximal cardiopulmonary exercise test performance. Data are reported as mean ± SEM. *p = 0.019, 2-way analysis of variance with post hoc Bonferroni tests. PVR = pulmonary...

Figure 2: MDL-28170 Protects Against Cardiac Stress–Induced Heart Failure

Yihui Wang, Biyi Chen, Chun-Kai Huang, Ang Guo, Jennifer Wu, Xiaoming Zhang, Rong Chen, Cheng Chen, William Kutschke, Robert M. Weiss, Ryan L. Boudreau, Kenneth B. Margulies, Jiang Hong & Long-Sheng Song
(A) Calpain activity was assessed in LV lysates after TAB, MI, or ISO minipump infusion. (B and C) Average heart weight/body weight (B) and lung weight/body weight (C) ratios at 5 weeks after surgery or 2 weeks after ISO minipump implantation. (D to F) End-systolic volume (ESV) (D), end-diastolic volume (EDV) (E), and ejection fraction (EF) (F) were assessed by echocardiography. n = 7 to 11 mice per group. For A, **p < 0.01 as...

Figure 7: Immunohistochemical Results for ISO Versus ISO/3AB (Summative Data)

Sven Y. Surikow, Thanh H. Nguyen, Irene Stafford, Matthew Chapman, Sujith Chacko, Kuljit Singh, Giovanni Licari, Betty Raman, Darren J. Kelly, Yuan Zhang, Mark T. Waddingham, Doan T. Ngo, Alexander P. Bate, Su Jen Chua, Michael P. Frenneaux & John D. Horowitz
Effects of ISO on regional accumulation of 3-NT, PAR, and TXNIP in left ventricular myocardium with 3AB (ISO/3AB) and without (ISO). (A) 3-NT, showing mean values at apex and base. Two-way ANOVA: 3AB, p = 0.44; apex/base, p = 0.17; and interaction, p = 0.18. (B) PAR mean values at apex and base. Two-way ANOVA: 3AB, p = 0.0001; apex/base, p = 0.0043; and interaction, p = 0.86. (C) TXNIP mean values at apex and...

Visual Abstract - Cardiac Nuclear High-Mobility Group Box 1 Ameliorates Pathological Cardiac Hypertrophy by Inhibiting DNA Damage Response: 10.1016/j.jacbts.2018.11.011

Tetsuya Takahashi, Tetsuro Shishido, Daisuke Kinoshita, Ken Watanabe, Taku Toshima, Takayuki Sugai, Taro Narumi, Yoichiro Otaki, Harutoshi Tamura, Satoshi Nishiyama, Takanori Arimoto, Hiroki Takahashi, Takuya Miyamoto, Tetsu Watanabe, Chang-Hoon Woo, Jun-Ichi Abe, Yasuchika Takeishi, Isao Kubota & Masafumi Watanabe
• HMGB1 is a DNA-binding protein associated with nuclear homeostasis and DNA repair.
• Decreased nuclear HMGB1 expression is observed in human failing hearts, which is associated with cardiomyocyte hypertrophy and fibrosis.
• Cardiac nuclear HMGB1 overexpression ameliorates Ang II–induced pathological cardiac remodeling by inhibiting cardiomyocyte DNA damage and following ataxia telangiectasia mutated activation in mice.
• Ataxia telangiectasia mutated inhibitor treatment provided a cardioprotective effect on Ang II–induced cardiac remodeling in mice.

Figure 4: Effect of ApoA-I Raising on Plasma Markers of Inflammation

Jamie Morton, Shisan Bao, Laura Z. Vanags, Tania Tsatralis, Anisyah Ridiandries, Chung-Wah Siu, Kwong-Man Ng, Joanne T.M. Tan, David S. Celermajer, Martin K.C. Ng & Christina A. Bursill
At sacrifice, plasma MCP-1 and SAA were measured using enzyme-linked immunosorbent assay in the late-stage model receiving apoA-I raising by infusions (A and B) or lentiviral gene-transfer (C and D), and in the early-stage model receiving apoA-I infusions (E and F). Data are mean ± SD. Baseline n = 3 to 5, saline n = 15, apoA-I n = 15, LVGFP n = 8, LVApoA-I n = 8 mice/treatment for apoA-I infusions study and n...

Figure 1: Functional Effects of ISO Alone

Sven Y. Surikow, Thanh H. Nguyen, Irene Stafford, Matthew Chapman, Sujith Chacko, Kuljit Singh, Giovanni Licari, Betty Raman, Darren J. Kelly, Yuan Zhang, Mark T. Waddingham, Doan T. Ngo, Alexander P. Bate, Su Jen Chua, Michael P. Frenneaux & John D. Horowitz
Echocardiographic strain data derived from apical myocardial motion in (A) pre-treated state and (B) 24-h post-injection of isoproterenol (ISO). Post-ISO analysis showed marked impairment of apical radial strain. Ant = anterior; AntSept = anteroseptal; AVC = aortic valve closure; Inf = inferior; Lat = lateral; Post = posterior; SAX-AP = short axis-apex; Sept = septal; SR = strain rate.

Figure 4: Structures of Biomaterials for MI and PAD Applications

Melissa J. Hernandez & Karen L. Christman
Biomaterial structures dictate important parameters including degradation and controlled release of therapeutics. The architecture, shown by scanning electron micrographs, varies among hydrogels, such as (A) keratin, (B) porcine-derived skeletal muscle extracellular matrix (ECM), (C) porcine-derived pericardial ECM, (D) collagen, (E) alginate, or (F) fibrin. Additionally, hydrogel architecture differs from particles like (G) poly(lactic-co-glycolic acid) microparticles or (H) acetalated dextran microparticles. Reproduced with permission from Shen et al. (29), DeQuach et al. (85), Seif-Naraghi et al....

Figure 2: Cartoon Representations of the Myocardial Fiber Architecture

Christopher T. Nguyen, James Dawkins, Xiaoming Bi, Eduardo Marbán & Debiao Li
(A) Normal and (B) infarcted left ventricle. α characterizes the inclination of the estimated myocardial fiber orientation of each voxel in relation to the short axis plane (defined by r and t) and tangent plane (defined by t and u). For normal myocardial fiber architecture, the helix angle smoothly changes from the endocardium (red) to mid-myocardium (green) to epicardium (blue). This transmural change is roughly linear and can be characterized by fitting a slope through...

Figure 4: POCT for Antithrombotic Therapy

Kevin R. King, Luanda P. Grazette, Dina N. Paltoo, John T. McDevitt, Samuel K. Sia, Paddy M. Barrett, Fred S. Apple, Paul A. Gurbel, Ralph Weissleder, Hilary Leeds, Erin J. Iturriaga, Anupama K. Rao, Bishow Adhikari, Patrice Desvigne-Nickens, Zorina S. Galis & Peter Libby
Many patients have indications for both anticoagulation (e.g., atrial fibrillation, venous thromboembolism, mechanical heart valve) and antiplatelet therapy (e.g., myocardial infarction or percutaneous coronary intervention). There is limited clinical trial data to guide the use of these agents in combination therapy. New diagnostics could aid selection and titration of combination regimens to personalize care by optimizing the risks of bleeding and clotting.

Figure 2: Successful Hydrogel Delivery to the Pericardial Space Using the Hydrogel Delivery Device Visualized Directly and by Fluoroscopy

Jose R. Garcia, Peter F. Campbell, Gautam Kumar, Jonathan J. Langberg, Liliana Cesar, Lanfang Wang, Andrés J. García & Rebecca D. Levit
(A) The delivery device was successfully placed over the left anterior descending artery in a porcine cadaver. Sternum was removed to allow direct visualization. (B) Contrast-labeled hydrogel delivery by the device (arrow) was visualized in situ by fluoroscopy. (C) In a live animal, trypan blue–labeled gel was delivered with the device to the posterior wall and gelled within the temporary compartment created by the device, epicardium, and pericardium. Sixty minutes after device removal, the gel...

Figure 4: HF Hearts Have an Increased Susceptibility to Ca-ALT, Which Is Prevented by RDN

Sheng-Nan Chang, Shu-Hsuan Chang, Chih-Chieh Yu, Cho-Kai Wu, Ling-Ping Lai, Fu-Tien Chiang, Juey-Jen Hwang, Jiunn-Lee Lin & Chia-Ti Tsai
(A) Representative calcium transient tracings at 333-ms and 130-ms pacing cycle length from CTL, HF, and HF+RDN hearts are shown. Significant calcium transient alternans (Ca-ALT) is seen in the HF heart (middle panel), but not in the CTL (upper panel), and HF+RDN (lower panel) hearts. (B) Summary data demonstrating the relationship of PR and Ca-ALT from CTL, HF, and HF+RDN hearts are shown. In HF hearts, more Ca-ALT is observed at each PR tested, and...

Figure 5: Cumulative Incidence Curves for Cardiovascular Death, MI, or Severe Recurrent Ischemia Leading to Urgent Revascularization Through 12 Weeks With Losmapimod Versus Placebo (LATITUDE-TIMI 60, Phase 3)

Jennifer A. Rymer & L. Kristin Newby
CI = confidence interval; LATITUDE-TIMI 60 = Losmapimod to Inhibit p38 MAP Kinase as a Therapeutic Target and Modify Outcomes After an Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 60; MI = myocardial infarction.

Figure 4: Effects of Short-Term L-Phe on Aortic and Mesenteric Vascular Reactivity

Lamia Heikal, Anna Starr, Dania Hussein, Jesus Prieto-Lloret, Phil Aaronson, Lea Ann Dailey & Manasi Nandi
Concentration response curves for acetylcholine in (A) WKY mesenteric rings, (B) SHR mesenteric rings, (C) WKY aortic rings, and (D) SHR aortic rings, with intact or denuded endothelium following short-term incubation with 0.5 mmol·l−1 L-phe. Data represent mean ± SEM n = 6 animals (in triplicate/animal) for mesenteric arteries and aortic rings (*p < 0.05 and *** p < 0.001 for the whole curve). Table (E) shows EC50 values (nmol·l−1) comparing saline control with L-phe...

Figure 5: Effects of Long-Term L-Phe Treatment on Aortic and Mesenteric Vascular Reactivity

Lamia Heikal, Anna Starr, Dania Hussein, Jesus Prieto-Lloret, Phil Aaronson, Lea Ann Dailey & Manasi Nandi
Concentration response curves for acetylcholine in (A) mesenteric arteries and (B) aortic rings isolated from L-phe treated long-term treated SHR and saline controls. The table (C) shows corresponding EC50 values (*p < 0.05). Data represent mean ± SD, n = 6 independent experiments (*p < 0.05 for the whole curve). Abbreviations as in Figures 1 and 4.

Figure 9: Effects of Acute VNS on NO Synthesis and Inflammation in the Lung

Keimei Yoshida, Keita Saku, Kazuhiro Kamada, Kohtaro Abe, Mariko Tanaka-Ishikawa, Takeshi Tohyama, Takuya Nishikawa, Takuya Kishi, Kenji Sunagawa & Hiroyuki Tsutsui
Values are mean ± SEM. Differences were tested by using Student’s t-test. ∗p < 0.05 and ∗∗p < 0.01 vs. SS. Effects of acute VNS (n = 3) or SS (n = 3) on nitric oxide (NO) synthesis in the lung of rats 5 weeks after SU5416 injection. Representative Western blotting of (A) endothelial nitric oxide synthase (eNOS) and (B) phosphorylated eNOS (p-eNOS) are shown in the upper panels. Graphs indicate semi-quantitative analysis of Western...

Figure 1: Slice Generation and Culture

R. Croft Thomas, Abhishek Singh, Patrick M. Cowley, Bat-Erdene Myagmar, Megan D. Montgomery, Philip M. Swigart, Teresa De Marco, Anthony J. Baker & Paul C. Simpson
(A) A coring tool is used to punch an 8-mm diameter “core” from pieces of left ventricular free wall, perpendicular to myofiber orientation. (B) The core is trimmed, imbedded in agarose, and placed in a holder of the Krumdieck slicer, submerged in cold slicing buffer. (C) The core is passed across a razor blade at the bottom of the core holder to cut slices, and cold buffer delivers them into a receiving dish. (D) Slices...

Figure 4: Circulating ALDH

Daniella C. Terenzi, Mohammed Al-Omran, Adrian Quan, Hwee Teoh, Subodh Verma & David A. Hess
(A to C) The frequency of circulating ALDHhiSSCmid cells co-expressing CD34 with the macrophage scavenger receptor (CD68) was decreased in patients with T2D compared with control subjects. (D to F) The frequency of circulating ALDHhiSSCmid cells co-expressing CD68 with the M1 macrophage–associated marker CD80 was equal in patients with T2D compared with control subjects. (G to I) The frequency of circulating ALDHhiSSCmid progenitor cells co-expressing CD68 with the M2 macrophage–associated marker CD163 was decreased in...

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