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
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2019

Open Access 01-12-2019 | Arthritis | Research article

The oncoprotein TBX3 is controlling severity in experimental arthritis

Authors: Samra Sardar, Alish Kerr, Daniëlle Vaartjes, Emilie Riis Moltved, Edita Karosiene, Ramneek Gupta, Åsa Andersson

Published in: Arthritis Research & Therapy | Issue 1/2019

Login to get access

Abstract

Background

Development of autoimmune diseases is the result of a complex interplay between hereditary and environmental factors, with multiple genes contributing to the pathogenesis in human disease and in experimental models for disease. The T-box protein 3 is a transcriptional repressor essential during early embryonic development, in the formation of bone and additional organ systems, and in tumorigenesis.

Methods

With the aim to find novel genes important for autoimmune inflammation, we have performed genetic studies of collagen-induced arthritis (CIA), a mouse experimental model for rheumatoid arthritis.

Results

We showed that a small genetic fragment on mouse chromosome 5, including Tbx3 and three additional protein-coding genes, is linked to severe arthritis and high titers of anti-collagen antibodies. Gene expression studies have revealed differential expression of Tbx3 in B cells, where low expression was accompanied by a higher B cell response upon B cell receptor stimulation in vitro. Furthermore, we showed that serum TBX3 levels rise concomitantly with increasing severity of CIA.

Conclusions

From these results, we suggest that TBX3 is a novel factor important for the regulation of gene transcription in the immune system and that genetic polymorphisms, resulting in lower expression of Tbx3, are contributing to a more severe form of CIA and high titers of autoantibodies. We also propose TBX3 as a putative diagnostic biomarker for rheumatoid arthritis.
Appendix
Available only for authorised users
Literature
1.
Klareskog L, Padyukov L, Lorentzen J, Alfredsson L. Mechanisms of disease: genetic susceptibility and environmental triggers in the development of rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006;2(8):425–33.PubMedCrossRef
2.
Newton JL, Harney SMJ, Wordsworth BP, Brown MA. A review of the MHC genetics of rheumatoid arthritis. Genes Immun. 2004;5(3):151–7.PubMedCrossRef
3.
Kochi Y, Suzuki A, Yamamoto K. Genetic basis of rheumatoid arthritis: a current review. Biochem Biophys Res Commun. 2014;452(2):254–62.PubMedCrossRef
4.
Besenyei T, Kadar A, Tryniszewska B, Kurko J, Rauch TA, Glant TT, et al. Non-MHC risk alleles in rheumatoid arthritis and in the syntenic chromosome regions of corresponding animal models. Clin Dev Immunol. 2012;2012:284751.PubMedPubMedCentralCrossRef
5.
Taylor PC, Moore A, Vasilescu R, Alvir J, Tarallo M. A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective. Rheumatol Int. 2016;36(5):685–95.PubMedPubMedCentralCrossRef
6.
Sardar S, Andersson Å. Old and new therapeutics for rheumatoid arthritis: in vivo models and drug development. Immunopharmacol Immunotoxicol. 2016;38(1):2–13.PubMedCrossRef
7.
Jirholt J, Cook A, Emahazion T, Sundvall M, Jansson L, Nordquist N, et al. Genetic linkage analysis of collagen-induced arthritis in the mouse. Eur J Immunol. 1998;28:3321–8.PubMedCrossRef
8.
Lindvall T, Karlsson J, Holmdahl R, Andersson Å. Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes. Arthritis Res Ther. 2009;11(1):R10.PubMedPubMedCentralCrossRef
9.
10.
Karlsson J, Zhao X, Lonskaya I, Neptin M, Holmdahl R, Andersson Å. Novel quantitative trait loci controlling development of experimental autoimmune encephalomyelitis and proportion of lymphocyte subpopulations. J Immunol. 2003;170(2):1019–26.PubMedCrossRef
11.
Davis MA, Larimore EA, Fissel BM, Swanger J, Taatjes DJ, Clurman BE. The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. Genes Dev. 2013;27(2):151–6.PubMedPubMedCentralCrossRef
12.
13.
14.
Neelamraju Y, Hashemikhabir S, Janga SC. The human RBPome: from genes and proteins to human disease. J Proteome. 2015;2015:61–70.CrossRef
15.
16.
Ghosh TK, Packham E, Bonser J, Robinson TE, Cross SJ, Brook JD. Characterization of the TBX5 binding site and analysis of mutations that cause Holt-Oram syndrome. Hum Mol Genet. 2001;10(18):1983–94.PubMedCrossRef
17.
Carlson H, Ota S, Campbell CE, Hurlin PJ. A dominant repression domain in Tbx3 mediates transcriptional repression and cell immortalization: relevance to mutations in Tbx3 that cause ulnar-mammary syndrome. Hum Mol Genet. 2001;10(21):2403–13.PubMedCrossRef
18.
Washkowitz AJ, Gavrilov S, Begum S, Papaioannou VE. Diverse functional networks of Tbx3 in development and disease. Wiley Interdiscip Rev Syst Biol Med. 2012;4(3):273–83.PubMedPubMedCentralCrossRef
19.
Chapman DL, Garvey N, Hancock S, Alexiou M, Agulnik SI, Gibson-Brown JJ, et al. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Dev Dyn. 1996;206(4):379–90.PubMedCrossRef
20.
Bickley SRB, Logan MPO. Regulatory modulation of the T-box gene Tbx5 links development, evolution, and adaptation of the sternum. Proc Natl Acad Sci U S A. 2014;111(50):17917–22.PubMedPubMedCentralCrossRef
21.
Denninger KCM, Litman T, Marstrand T, Moller K, Svensson L, Labuda T, et al. Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis. Arthritis Res Ther. 2015;17:43.PubMedPubMedCentralCrossRef
22.
Frank DU, Emechebe U, Thomas KR, Moon AM. Mouse Tbx3 mutants suggest novel molecular mechanisms for ulnar-mammary syndrome. PLoS One. 2013;8(7):1–7.
23.
D’Amelio P, Sassi F. Osteoimmunology: from mice to humans. Bonekey Rep. 2016;5:1–6.CrossRef
24.
Lomnytska M, Dubrovska A, Hellman U, Volodko N, Souchelnytskyi S. Increased expression of cSHMT, Tbx3 and utrophin in plasma of ovarian and breast cancer patients. Int J Cancer. 2006;118(2):412–21.PubMedCrossRef
25.
Willmer T, Cooper A, Sims D, Govender D, Prince S. The T-box transcription factor 3 is a promising biomarker and a key regulator of the oncogenic phenotype of a diverse range of sarcoma subtypes. Oncogene. 2016;5(2):e199.CrossRef
26.
Thomsen N, Ali RG, Ahmed JN, Arkell RM. High Resolution Melt Analysis (HRMA); a Viable Alternative to Agarose Gel Electrophoresis for Mouse Genotyping. PLoS One. 2012;7(9):e45252.PubMedPubMedCentralCrossRef
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
Dahdah A, Habir K, Nandakumar KS, Saxena A, Xu B, Holmdahl R, et al. Germinal center B cells are essential for collagen-induced arthritis. Arthritis Rheumatol. 2018;70(2):193–203.PubMedCrossRef
37.
Li J, Weinberg MS, Zerbini L, Prince S. The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway. Mol Biol Cell. 2013;24:3569–76.PubMedPubMedCentralCrossRef
38.
Tümpel S, Sanz-Ezquerro JJ, Isaac A, Eblaghie MC, Dobson J, Tickle C. Regulation of Tbx3 expression by anteroposterior signalling in vertebrate limb development. Dev Biol. 2002;250(2):251–62.PubMedCrossRef
39.
Lee HS, Cho HH, Kim HK, Bae YC, Baik HS, Jung JS. Tbx3, a transcriptional factor, involves in proliferation and osteogenic differentiation of human adipose stromal cells. Mol Cell Biochem. 2007;296(1–2):129–36.PubMedCrossRef
40.
Renard CA, Labalette C, Armengol C, Cougot D, Wei Y, Cairo S, et al. Tbx3 is a downstream target of the Wnt/β-catenin pathway and a critical mediator of β-catenin survival functions in liver cancer. Cancer Res. 2007;67(3):901–10.PubMedCrossRef
41.
Lüdtke TH, Rudat C, Wojahn I, Weiss AC, Kleppa MJ, Kurz J, et al. Tbx2 and Tbx3 Act downstream of Shh to maintain canonical Wnt signaling during branching morphogenesis of the murine lung. Dev Cell. 2016;39(2):239–53.PubMedCrossRef
42.
Brand DD, Kang AH, Rosloniec EF. The mouse model of collagen-induced arthritis. Methods Mol Med. 2004;102(1):295–312.PubMed
43.
44.
45.
Ma Y, Bramwell KK, Lochhead RB, Paquette JK, Zachary JF, Weis JH, Teuscher C, Weis JJ. Borrelia burgdorferi arthritis associated locus Bbaa1 regulates Lyme arthritis and K/B×N serum transfer arthritis through intrinsic control of type I IFN production. J Immunol. 2014;193(12):6050–60.PubMedPubMedCentralCrossRef
46.
Sardar S, Kanne K, Andersson Å. Analysis of polymorphisms in the Mediator complex subunit 13-like (Med13L) gene in the context of immune function and development of experimental arthritis. Arch Immunol Ther Exp. 2018;66(5):365–77.CrossRef
47.
Abiola O, Angel JM, Avner P, Bachmanov AA, Belknap JK, Bennett B, et al. The nature and identification of quantitative trait loci: a community’s view. Nat Rev Genet. 2003;4(11):911–6.PubMedCrossRef
48.
Panayi GS. B cells: a fundamental role in the pathogenesis of rheumatoid arthritis? Rheumatology (Oxford). 2005;44(Suppl 2):ii3–7.CrossRef
49.
Bugatti S, Vitolo B, Caporali R. B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. Biomed Res. 2014;2014:681678.
50.
Burmester GR, Feist E, Dörner T. Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol. 2014;10(2):77–88.PubMedCrossRef
51.
52.
Kurosaki T. Regulation of B-cell signal transduction by adaptor proteins. Nat Rev Immunol. 2002;2:354.PubMedCrossRef
53.
Satpathy S, Wagner SA, Beli P, Gupta R, Kristiansen TA, Malinova D, et al. Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation. Mol Syst Biol. 2015;11(6):810.PubMedPubMedCentralCrossRef
54.
Chang F, Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia. 2003;17(3):590–603.PubMedCrossRef
55.
56.
Peres J, Mowla S, Prince S. The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis. Oncotarget. 2014;6(3):1821–33.PubMedCentral
57.
Niwa H, Ogawa K, Shimosato D, Adachi K. A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature. 2009;460(7251):118–22.PubMedCrossRef
58.
Ito A, Asamoto M, Hokaiwado N, Takahashi S, Shirai T. Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells. Cancer Lett. 2005;219(1):105–12.PubMedCrossRef
59.
Fan W, Huang X, Chen C, Gray J, Huang T. TBX3 and its isoform TBX3 + 2a are functionally distinctive in inhibition of senescence and are overexpressed in a subset of breast CANCER CELL LInes. Cancer Res. 2004;64(15):5132–9.PubMedCrossRef
60.
Carlson H, Ota S, Song Y, Chen Y, Hurlin PJ. Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation. Oncogene. 2002;21(24):3827–35.PubMedCrossRef
61.
Brummelkamp TR, Kortlever RM, Lingbeek M, Trettel F, MacDonald ME, Van Lohuizen M, et al. TBX-3, the gene mutated in ulnar-mammary syndrome, is a negative regulator of p19ARF and inhibits senescence. J Biol Chem. 2002;277(8):6567–72.PubMedCrossRef
62.
Wensing LA, Campos AH. TBX3, a downstream target of TGF-beta1, inhibits mesangial cell apoptosis. Exp Cell Res. 2014;328(2):340–50.PubMedCrossRef
63.
Li J, Ballim D, Rodriguez M, Cui R, Goding CR, Teng H, et al. The anti-proliferative function of the tgf-β1 signaling pathway involves the repression of the oncogenic tbx2 by its homologue tbx3. J Biol Chem. 2014;289(51):35633–43.PubMedPubMedCentralCrossRef
64.
Palm A-KE, Friedrich HC, Mezger A, Salomonsson M, Myers LK, Kleinau S. Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis. Cell Mol Immunol. 2015;12(4):493–504.PubMedPubMedCentralCrossRef
65.
Robert P, Seielstad M, Lee T, D P, Remmers EF, Ding B, et al. TRAF1-C5 as a risk locus for rheumatoid arthritis — a genomewide study. N Engl J Med 2007;357(12):1199–1209.
66.
Freudenberg J, Lee HS, Han BG, Shin H, Do KYM, Sung YK, et al. Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci. Arthritis Rheum. 2011;63(4):884–93.PubMedCrossRef
67.
Julia A, Ballina J, Caete JD, Balsa A, Tornero-Molina J, Naranjo A, et al. Genome-wide association study of rheumatoid arthritis in the Spanish population: KLF12 as a risk locus for rheumatoid arthritis susceptibility. Arthritis Rheum. 2008;58(8):2275–86.PubMedCrossRef
68.
Kumar P, Franklin S, Emechebe U, Hu H, Moore B, Lehman C, et al. TBX3 regulates splicing in vivo: a novel molecular mechanism for ulnar-mammary syndrome. PLoS Genet. 2014;10(3):e1004247.CrossRef
69.
Govoni KE, Lee SK, Chadwick RB, Yu H, Kasukawa Y, Baylink DJ, et al. Whole genome microarray analysis of growth hormone-induced gene expression in bone: T-box3, a novel transcription factor, regulates osteoblast proliferation. Am J Physiol Endocrinol Metab. 2006;291(1):E128–36.PubMedPubMedCentralCrossRef
70.
Govoni KE, Linares GR, Chen ST, Pourteymoor S, Mohan S. T-box 3 negatively regulates osteoblast differentiation by inhibiting expression of osterix and runx2. J Cell Biochem. 2009;106(3):482–90.PubMedPubMedCentralCrossRef
71.
Yao C, Yao GQ, Sun BH, Zhang C, Tommasini SM, Insogna K. The transcription factor T-box 3 regulates colony-stimulating factor 1-dependent Jun dimerization protein 2 expression and plays an important role in osteoclastogenesis. J Biol Chem. 2014;289(10):6775–90.PubMedPubMedCentralCrossRef
72.
Freudenberg J, Lee H-S, Han B-G, Do SH, Kang YM, Sung Y-K, et al. Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci. Arthritis Rheum. 2011;63(4):884–93.PubMedCrossRef
73.
Haas CS, Creighton CJ, Pi X, Maine I, Koch AE, Haines GK, et al. Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease-discordant monozygotic twins. Arthritis Rheum. 2006;54(7):2047–60.PubMedCrossRef
74.
Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther. 2007;9(1):204.PubMedPubMedCentralCrossRef
75.
Georges R, Nemer G, Morin M, Lefebvre C, Nemer M. Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation. Mol Cell Biol. 2008;28(12):4052–67.PubMedPubMedCentralCrossRef
76.
Hoffmann AD, Yang XH, Burnicka-Turek O, Bosman JD, Ren X, Steimle JD, et al. Foxf genes integrate Tbx5 and Hedgehog pathways in the second heart field for cardiac septation. PLoS Genet. 2014;10(10):e1004604.PubMedPubMedCentralCrossRef
77.
Nishimoto S, Wilde SM, Wood S, Logan MPO. RA Acts in a coherent feed-forward mechanism with Tbx5 to control limb bud induction and initiation. Cell Rep. 2015;12(5):879–91.PubMedPubMedCentralCrossRef
78.
Zhang KK, Xiang M, Zhou L, Liu J, Curry N, Heine Suñer D, et al. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation. Hum Mol Genet. 2015;25(6):1140–51.CrossRef
79.
Pizard A, Burgon PG, Paul DL, Bruneau BG, Seidman CE, Seidman JG. Connexin 40, a target of transcription factor Tbx5, patterns wrist, digits, and sternum. Mol Cell Biol. 2005;25(12):5073–83.PubMedPubMedCentralCrossRef
80.
Bruneau BG, Nemer G, Schmitt JP, Charron F, Robitaille L, Caron S, et al. A murine model of Holt-Oram syndrome defines roles of the T-Box transcription factor Tbx5 in cardiogenesis and disease. Cell. 2001;106(6):709–21.PubMedCrossRef
81.
Moskowitz IPG, Pizard A, Patel VV, Bruneau BG, Kim JB, Kupershmidt S, et al. The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Development. 2004;131(16):4107–16.PubMedCrossRef
82.
Rangkasenee N, Murani E, Brunner RM, Schellander K, Cinar MU, Luther H, et al. Genome-wide association identifies TBX5 as candidate gene for osteochondrosis providing a functional link to cartilage perfusion as initial factor. Front Genet. 2013;4:78.PubMedPubMedCentralCrossRef
83.
Karouzakis E, Trenkmann M, Gay RE, Michel BA, Gay S, Neidhart M. Epigenome analysis reveals TBX5 as a novel transcription factor involved in the activation of rheumatoid arthritis synovial fibroblasts. J Immunol. 2014;193(10):4945–51.PubMedCrossRef
84.
Kallberg Y, Segerstolpe Å, Lackmann F, Persson B, Wieslander L. Evolutionary conservation of the ribosomal biogenesis factor Rbm19/Mrd1: implications for function. PLoS One. 2012;7(9):e43786.PubMedPubMedCentralCrossRef
85.
Pausch H, Emmerling R, Schwarzenbacher H, Fries R. A multi-trait meta-analysis with imputed sequence variants reveals twelve QTL for mammary gland morphology in Fleckvieh cattle. Genet Sel Evol. 2016;48(1):14.PubMedPubMedCentralCrossRef
86.
Campbell IK, Gerondakis S, O’Donnell K, Wicks IP. Distinct roles for the NF-kappaB1 (p50) and c-Rel transcription factors in inflammatory arthritis. J Clin Invest. 2000;105(12):1799–806.PubMedPubMedCentralCrossRef
87.
Cao G, Dong W, Meng X, Liu H, Liao H, Liu S. MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by targeting PIK3R3. Tumour Biol. 2015;36(6):4453–9.PubMedCrossRef
88.
Wagner EF, Robert E. Fos/AP-1 proteins in bone and the immune system. Immunol Rev. 2005;208:26–140.CrossRef
89.
90.
Metadata
Title
The oncoprotein TBX3 is controlling severity in experimental arthritis
Authors
Samra Sardar
Alish Kerr
Daniëlle Vaartjes
Emilie Riis Moltved
Edita Karosiene
Ramneek Gupta
Åsa Andersson
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2019
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-018-1797-3

Other articles of this Issue 1/2019

Arthritis Research & Therapy 1/2019 Go to the issue

Research article

Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden

Research article

European Network of Pregnancy Registers in Rheumatology (EuNeP)—an overview of procedures and data collection

Research article

Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs

Research article

Juvenile idiopathic arthritis associated with a mutation in GATA3

Research article

Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiative—a prospective cohort study

Correction

Correction to: Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse posttraumatic osteoarthritis model
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