Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Cardiomyopathy | Research

Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide

Authors: Angela S. Maione, Pawan Faris, Lara Iengo, Valentina Catto, Luca Bisonni, Francesco Lodola, Sharon Negri, Michela Casella, Anna Guarino, Gianluca Polvani, Marina Cerrone, Claudio Tondo, Giulio Pompilio, Elena Sommariva, Francesco Moccia

Published in: Journal of Translational Medicine | Issue 1/2022

Login to get access

Abstract

Background

Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca2+) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown.
Thus, we aim to ascertain whether intracellular Ca2+ oscillations and the Ca2+ toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes.

Methods and results

ACM C-MSC show enhanced spontaneous Ca2+ oscillations and concomitant increased Ca2+/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca2+ Entry (SOCE), which leads to enhanced Ca2+ release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca2+ handling machinery or CaMKII activity, we demonstrated a causative link between Ca2+ oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca2+ signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca2+ oscillations and fibro-adipogenic differentiation by selectively targeting SOCE.

Conclusions

Altogether, our results extend the knowledge of Ca2+ dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM.
Appendix
Available only for authorised users
Literature
1.
2.
Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, et al. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res. 2005;65(2):366–73.PubMedCrossRef
3.
Bennett RG, Haqqani HM, Berruezo A, Della Bella P, Marchlinski FE, Hsu CJ, et al. Arrhythmogenic Cardiomyopathy in 2018–2019: ARVC/ALVC or Both? Heart Lung Circ. 2019;28(1):164–77.PubMedCrossRef
4.
Delmar M, Alvarado FJ, Valdivia HH. Desmosome-Dyad Crosstalk: an arrhythmogenic axis in arrhythmogenic right ventricular cardiomyopathy. Circulation. 2020;141(18):1494–7.PubMedCrossRef
5.
Montnach J, Agullo-Pascual E, Tadros R, Bezzina CR, Delmar M. Bioinformatic analysis of a plakophilin-2-dependent transcription network: implications for the mechanisms of arrhythmogenic right ventricular cardiomyopathy in humans and in boxer dogs. Europace: European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiolo. 2018;20(suppl_3):iii125–32.CrossRef
6.
van Opbergen CJM, Noorman M, Pfenniger A, Copier JS, Vermij SH, Li Z, et al. Plakophilin-2 haploinsufficiency causes calcium handling deficits and modulates the cardiac response towards stress. Int J Mol Sci. 2019;20(17):4076.PubMedCentralCrossRef
7.
Kim JC, Perez-Hernandez M, Alvarado FJ, Maurya SR, Montnach J, Yin Y, et al. Disruption of Ca(2+)i Homeostasis and Connexin 43 Hemichannel function in the right ventricle precedes overt arrhythmogenic cardiomyopathy in plakophilin-2-deficient mice. Circulation. 2019;140(12):1015–30.PubMedPubMedCentralCrossRef
8.
Cerrone M, Marron-Linares GM, van Opbergen CJM, Costa S, Bourfiss M, Perez-Hernandez M, et al. Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study. Eur Heart J. 2022;43(12):1251–64.PubMedCrossRef
9.
Lyon A, van Opbergen CJM, Delmar M, Heijman J, van Veen TAB. In silico identification of disrupted myocardial calcium homeostasis as proarrhythmic trigger in arrhythmogenic cardiomyopathy. Front Physiol. 2021;12: 732573.PubMedPubMedCentralCrossRef
10.
Wang Y, Li C, Shi L, Chen X, Cui C, Huang J, et al. Integrin beta1D Deficiency-Mediated RyR2 dysfunction contributes to catecholamine-sensitive ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy. Circulation. 2020;141(18):1477–93.PubMedPubMedCentralCrossRef
11.
Sommariva E, Brambilla S, Carbucicchio C, Gambini E, Meraviglia V, Dello Russo A, et al. Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy. Eur Heart J. 2016;37(23):1835–46.PubMedCrossRef
12.
Maione AS, Stadiotti I, Pilato CA, Perrucci GL, Saverio V, Catto V, et al. Excess TGF-beta1 drives cardiac mesenchymal stromal cells to a pro-fibrotic commitment in arrhythmogenic cardiomyopathy. Int J Mol Sci. 2021;22(5):2673.PubMedPubMedCentralCrossRef
13.
Sun S, Liu Y, Lipsky S, Cho M. Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cells. FASEB J. 2007;21(7):1472–80.PubMedCrossRef
14.
Kawano S, Otsu K, Shoji S, Yamagata K, Hiraoka M. Ca(2+) oscillations regulated by Na(+)-Ca(2+) exchanger and plasma membrane Ca(2+) pump induce fluctuations of membrane currents and potentials in human mesenchymal stem cells. Cell Calcium. 2003;34(2):145–56.PubMedCrossRef
15.
Hanna H, Mir LM, Andre FM. In vitro osteoblastic differentiation of mesenchymal stem cells generates cell layers with distinct properties. Stem Cell Res Ther. 2018;9(1):203.PubMedPubMedCentralCrossRef
16.
Grajales L, Garcia J, Banach K, Geenen DL. Delayed enrichment of mesenchymal cells promotes cardiac lineage and calcium transient development. J Mol Cell Cardiol. 2010;48(4):735–45.PubMedPubMedCentralCrossRef
17.
Kawano S, Shoji S, Ichinose S, Yamagata K, Tagami M, Hiraoka M. Characterization of Ca(2+) signaling pathways in human mesenchymal stem cells. Cell Calcium. 2002;32(4):165–74.PubMedCrossRef
18.
Peng H, Hao Y, Mousawi F, Roger S, Li J, Sim JA, et al. Purinergic and Store-Operated Ca(2+) signaling mechanisms in mesenchymal stem cells and their roles in ATP-induced stimulation of cell migration. Stem Cells. 2016;34(8):2102–14.PubMedCrossRef
19.
20.
Tan YZ, Fei DD, He XN, Dai JM, Xu RC, Xu XY, et al. L-type voltage-gated calcium channels in stem cells and tissue engineering. Cell Prolif. 2019;52(4): e12623.PubMedPubMedCentralCrossRef
21.
Bohm J, Chevessier F, De Paula AM, Koch C, Attarian S, Feger C, et al. Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am J Hum Genet. 2013;92(2):271–8.PubMedPubMedCentralCrossRef
22.
Nesin V, Wiley G, Kousi M, Ong EC, Lehmann T, Nicholl DJ, et al. Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis. Proc Natl Acad Sci U S A. 2014;111(11):4197–202.PubMedPubMedCentralCrossRef
23.
De Koninck P, Schulman H. Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations. Science. 1998;279(5348):227–30.PubMedCrossRef
24.
25.
26.
Mustroph J, Neef S, Maier LS. CaMKII as a target for arrhythmia suppression. Pharmacol Ther. 2017;176:22–31.PubMedCrossRef
27.
Aji K, Maimaijiang M, Aimaiti A, Rexiati M, Azhati B, Tusong H, et al. Differentiation of human adipose derived stem cells into smooth muscle cells is modulated by CaMKIIgamma. Stem Cells Int. 2016;2016:1267480.PubMedPubMedCentralCrossRef
28.
Ho KYL, Khadilkar RJ, Carr RL, Tanentzapf G. A gap-junction-mediated, calcium-signaling network controls blood progenitor fate decisions in hematopoiesis. Current Biol: CB. 2021;31(21):4697-4712.e6.CrossRef
29.
Zhang F, Ye J, Meng Y, Ai W, Su H, Zheng J, et al. Calcium Supplementation Enhanced adipogenesis and improved glucose homeostasis through activation of camkii and PI3K/Akt signaling pathway in porcine bone marrow mesenchymal stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD). Cell Physiol Biochem. 2018;51(1):154–72.PubMedCrossRef
30.
31.
Zuccolo E, Bottino C, Diofano F, Poletto V, Codazzi AC, Mannarino S, et al. Constitutive Store-Operated Ca(2+) Entry Leads to enhanced nitric oxide production and proliferation in infantile hemangioma-derived endothelial colony-forming cells. Stem Cells Dev. 2016;25(4):301–19.PubMedCrossRef
32.
Balducci V, Faris P, Balbi C, Costa A, Negri S, Rosti V, et al. The human amniotic fluid stem cell secretome triggers intracellular Ca(2+) oscillations, NF-kappaB nuclear translocation and tube formation in human endothelial colony-forming cells. J Cell Mol Med. 2021;25(16):8074–86.PubMedPubMedCentralCrossRef
33.
Zuccolo E, Kheder DA, Lim D, Perna A, Nezza FD, Botta L, et al. Glutamate triggers intracellular Ca(2+) oscillations and nitric oxide release by inducing NAADP- and InsP3 -dependent Ca(2+) release in mouse brain endothelial cells. J Cell Physiol. 2019;234(4):3538–54.PubMedCrossRef
34.
Kawano S, Otsu K, Kuruma A, Shoji S, Yanagida E, Muto Y, et al. ATP autocrine/paracrine signaling induces calcium oscillations and NFAT activation in human mesenchymal stem cells. Cell Calcium. 2006;39(4):313–24.PubMedCrossRef
35.
Jiang LH, Hao Y, Mousawi F, Peng H, Yang X. Expression of P2 Purinergic receptors in mesenchymal stem cells and their roles in extracellular nucleotide regulation of cell functions. J Cell Physiol. 2017;232(2):287–97.PubMedCrossRef
36.
Moccia F, Baruffi S, Spaggiari S, Coltrini D, Berra-Romani R, Signorelli S, et al. P2y1 and P2y2 receptor-operated Ca2+ signals in primary cultures of cardiac microvascular endothelial cells. Microvasc Res. 2001;61(3):240–52.PubMedCrossRef
37.
Berra-Romani R, Raqeeb A, Avelino-Cruz JE, Moccia F, Oldani A, Speroni F, et al. Ca2+ signaling in injured in situ endothelium of rat aorta. Cell Calcium. 2008;44(3):298–309.PubMedCrossRef
38.
Dupont G, Houart G, De Koninck P. Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations: a simple model. Cell Calcium. 2003;34(6):485–97.PubMedCrossRef
39.
Tombes RM, Faison MO, Turbeville JM. Organization and evolution of multifunctional Ca(2+)/CaM-dependent protein kinase genes. Gene. 2003;322:17–31.PubMedCrossRef
40.
Backs J, Backs T, Neef S, Kreusser MM, Lehmann LH, Patrick DM, et al. The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc Natl Acad Sci U S A. 2009;106(7):2342–7.PubMedPubMedCentralCrossRef
41.
Edman CF, Schulman H. Identification and characterization of delta B-CaM kinase and delta C-CaM kinase from rat heart, two new multifunctional Ca2+/calmodulin-dependent protein kinase isoforms. Biochim Biophys Acta. 1994;1221(1):89–101.PubMedCrossRef
42.
Ermakov S, Gerstenfeld EP, Svetlichnaya Y, Scheinman MM. Use of flecainide in combination antiarrhythmic therapy in patients with arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm. 2017;14(4):564–9.PubMedCrossRef
43.
Watanabe H, Chopra N, Laver D, Hwang HS, Davies SS, Roach DE, et al. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med. 2009;15(4):380–3.PubMedPubMedCentralCrossRef
44.
Kryshtal DO, Blackwell DJ, Egly CL, Smith AN, Batiste SM, Johnston JN, et al. RYR2 channel inhibition is the principal mechanism of flecainide action in CPVT. Circ Res. 2021;128(3):321–31.PubMedCrossRef
45.
Salvage SC, Chandrasekharan KH, Jeevaratnam K, Dulhunty AF, Thompson AJ, Jackson AP, et al. Multiple targets for flecainide action: implications for cardiac arrhythmogenesis. Br J Pharmacol. 2018;175(8):1260–78.PubMedCrossRef
46.
Cerrone M, Montnach J, Lin X, Zhao YT, Zhang M, Agullo-Pascual E, et al. Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm. Nat Commun. 2017;8(1):106.PubMedPubMedCentralCrossRef
47.
Stadiotti I, Di Bona A, Pilato CA, Scalco A, Guarino A, Micheli B, et al. Neuropeptide Y promotes adipogenesis of human cardiac mesenchymal stromal cells in arrhythmogenic cardiomyopathy. Int J Cardiol. 2021;342:94–102.PubMedCrossRef
48.
Sommariva E, Stadiotti I, Casella M, Catto V, Dello Russo A, Carbucicchio C, et al. Oxidized LDL-dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy. EMBO Mol Med. 2021;13(9): e14365.PubMedPubMedCentralCrossRef
49.
Lombardi R, Chen SN, Ruggiero A, Gurha P, Czernuszewicz GZ, Willerson JT, et al. Cardiac Fibro-adipocyte progenitors express desmosome proteins and preferentially differentiate to adipocytes upon deletion of the desmoplakin gene. Circ Res. 2016;119(1):41–54.PubMedPubMedCentralCrossRef
50.
Cerrone M, Lin X, Zhang M, Agullo-Pascual E, Pfenniger A, Chkourko Gusky H, et al. Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype. Circulation. 2014;129(10):1092–103.PubMedCrossRef
51.
Austin KM, Trembley MA, Chandler SF, Sanders SP, Saffitz JE, Abrams DJ, et al. Molecular mechanisms of arrhythmogenic cardiomyopathy. Nat Rev Cardiol. 2019;16(9):519–37.PubMedPubMedCentralCrossRef
52.
Moccia F, Ruffinatti FA, Zuccolo E. Intracellular Ca(2)(+) signals to reconstruct a broken heart: still a theoretical approach? Curr Drug Targets. 2015;16(8):793–815.PubMedCrossRef
53.
Colella M, Grisan F, Robert V, Turner JD, Thomas AP, Pozzan T. Ca2+ oscillation frequency decoding in cardiac cell hypertrophy: role of calcineurin/NFAT as Ca2+ signal integrators. Proc Natl Acad Sci USA. 2008;105(8):2859–64.PubMedPubMedCentralCrossRef
54.
Rusciano MR, Sommariva E, Douin-Echinard V, Ciccarelli M, Poggio P, Maione AS. CaMKII activity in the inflammatory response of cardiac diseases. Int J Mol Sci. 2019;20(18):4374.PubMedCentralCrossRef
55.
Cipolletta E, Rusciano MR, Maione AS, Santulli G, Sorriento D, Del Giudice C, et al. Targeting the CaMKII/ERK interaction in the heart prevents cardiac hypertrophy. PLoS ONE. 2015;10(6): e0130477.PubMedPubMedCentralCrossRef
56.
Ljubojevic S, Radulovic S, Leitinger G, Sedej S, Sacherer M, Holzer M, et al. Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the development of hypertrophy and heart failure. Circulation. 2014;130(3):244–55.PubMedPubMedCentralCrossRef
57.
Li X, Holmes WR. Biophysical attributes that affect CaMKII activation deduced with a novel spatial stochastic simulation approach. PLoS Comput Biol. 2018;14(2): e1005946.PubMedPubMedCentralCrossRef
58.
Mignen O, Constantin B, Potier-Cartereau M, Penna A, Gautier M, Gueguinou M, et al. Constitutive calcium entry and cancer: updated views and insights. Eur BiophysJ : EBJ. 2017;46(5):395–413.CrossRef
59.
Correll RN, Goonasekera SA, van Berlo JH, Burr AR, Accornero F, Zhang H, et al. STIM1 elevation in the heart results in aberrant Ca(2)(+) handling and cardiomyopathy. J Mol Cell Cardiol. 2015;87:38–47.PubMedPubMedCentralCrossRef
60.
61.
El-Battrawy I, Zhao Z, Lan H, Cyganek L, Tombers C, Li X, et al. Electrical dysfunctions in human-induced pluripotent stem cell-derived cardiomyocytes from a patient with an arrhythmogenic right ventricular cardiomyopathy. Europace. 2018;20(FI1):f46–56.PubMedCrossRef
62.
Kim C, Wong J, Wen J, Wang S, Wang C, Spiering S, et al. Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature. 2013;494(7435):105–10.PubMedPubMedCentralCrossRef
63.
Chen P, Xiao Y, Wang Y, Zheng Z, Chen L, Yang X, et al. Intracellular calcium current disorder and disease phenotype in OBSCN mutant iPSC-based cardiomyocytes in arrhythmogenic right ventricular cardiomyopathy. Theranostics. 2020;10(24):11215–29.PubMedPubMedCentralCrossRef
64.
Hwang HS, Hasdemir C, Laver D, Mehra D, Turhan K, Faggioni M, et al. Inhibition of cardiac Ca2+ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol. 2011;4(2):128–35.PubMedPubMedCentralCrossRef
65.
Liu N, Denegri M, Ruan Y, Avelino-Cruz JE, Perissi A, Negri S, et al. Short communication: flecainide exerts an antiarrhythmic effect in a mouse model of catecholaminergic polymorphic ventricular tachycardia by increasing the threshold for triggered activity. Circ Res. 2011;109(3):291–5.PubMedCrossRef
66.
Moreau A, Reisqs JB, Delanoe-Ayari H, Pierre M, Janin A, Deliniere A, et al. Deciphering DSC2 arrhythmogenic cardiomyopathy electrical instability: from ion channels to ECG and tailored drug therapy. Clin Transl Med. 2021;11(3): e319.PubMedPubMedCentralCrossRef
67.
Goldstein S, Brooks MM, Ledingham R, Kennedy HL, Epstein AE, Pawitan Y, et al. Association between ease of suppression of ventricular arrhythmia and survival. Circulation. 1995;91(1):79–83.PubMedCrossRef
68.
Wichter T, Borggrefe M, Haverkamp W, Chen X, Breithardt G. Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. Circulation. 1992;86(1):29–37.PubMedCrossRef
69.
Morganroth J, Anderson JL, Gentzkow GD. Classification by type of ventricular arrhythmia predicts frequency of adverse cardiac events from flecainide. J Am Coll Cardiol. 1986;8(3):607–15.PubMedCrossRef
70.
Rolland T, Badenco N, Maupain C, Duthoit G, Waintraub X, Laredo M, et al. Safety and efficacy of flecainide associated with beta-blockers in arrhythmogenic right ventricular cardiomyopathy. Europace. 2022;24(2):278–84.PubMed
71.
72.
van der Voorn SM, Te Riele A, Basso C, Calkins H, Remme CA, van Veen TAB. Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification and therapy. Cardiovasc Res. 2020;116(9):1571–84.PubMedPubMedCentralCrossRef
73.
74.
Zhang W, Chen DQ, Qi F, Wang J, Xiao WY, Zhu WZ. Inhibition of calcium-calmodulin-dependent kinase II suppresses cardiac fibroblast proliferation and extracellular matrix secretion. J Cardiovasc Pharmacol. 2010;55(1):96–105.PubMedCrossRef
75.
Cao L, Chen Y, Lu L, Liu Y, Wang Y, Fan J, et al. Angiotensin II upregulates fibroblast-myofibroblast transition through Cx43-dependent CaMKII and TGF-beta1 signaling in neonatal rat cardiac fibroblasts. Acta Biochim Biophys Sin (Shanghai). 2018;50(9):843–52.CrossRef
76.
Moccia F, Lodola F, Stadiotti I, Pilato CA, Bellin M, Carugo S, et al. Calcium as a key player in arrhythmogenic cardiomyopathy: adhesion disorder or intracellular alteration? Int J Mol Sci. 2019;20(16):3986.PubMedCentralCrossRef
77.
Metadata
Title
Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide
Authors
Angela S. Maione
Pawan Faris
Lara Iengo
Valentina Catto
Luca Bisonni
Francesco Lodola
Sharon Negri
Michela Casella
Anna Guarino
Gianluca Polvani
Marina Cerrone
Claudio Tondo
Giulio Pompilio
Elena Sommariva
Francesco Moccia
Publication date
01-12-2022
Publisher
BioMed Central
Keyword
Cardiomyopathy
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03742-8

Other articles of this Issue 1/2022

Journal of Translational Medicine 1/2022 Go to the issue

Research

A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Research

Effects of a 4400 km ultra-cycling non-competitive race and related training on body composition and circulating progenitors differentiation

Research

FOXO transcriptional activity is associated with response to chemoradiation in EAC

Research

Genome-wide association study reveals ethnicity-specific SNPs associated with ankylosing spondylitis in the Taiwanese population

Correction

Correction to: Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations

Research

Extracellular vesicles from the inflammatory microenvironment regulate the osteogenic and odontogenic differentiation of periodontal ligament stem cells by miR-758-5p/LMBR1/BMP2/4 axis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits