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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Immunology
Published in: BMC Immunology 1/2020

Open Access 01-12-2020 | Human Immunodeficiency Virus | Research article

Small RNA sequencing of extracellular vesicles identifies circulating miRNAs related to inflammation and oxidative stress in HIV patients

Authors: Sukrutha Chettimada, David R. Lorenz, Vikas Misra, Steven M. Wolinsky, Dana Gabuzda

Published in: BMC Immunology | Issue 1/2020

Login to get access

Abstract

Background

Extracellular vesicles (EVs) are nano-sized particles secreted by most cells. EVs carry nucleic acids that hold promise as potential biomarkers in various diseases. Human immunodeficiency virus type 1 (HIV) infects CD4+ T cells and induces immune dysfunction, inflammation, and EV secretion, but little is known about EV small RNA cargo in relation to immune dysregulation in HIV-infected individuals. Here, we characterize small RNA carried by circulating EVs in HIV-positive subjects on antiretroviral therapy (ART) relative to uninfected controls by next-generation RNA sequencing.

Results

Plasma EVs isolated from HIV-positive and HIV-negative subjects in test (n = 24) and validation (n = 16) cohorts were characterized by electron microscopy, nanoparticle tracking analysis, and immunoblotting for exosome markers. EVs were more abundant in plasma from HIV-positive compared to HIV-negative subjects. Small RNA sequencing of plasma EVs in the test cohort identified diverse small RNA species including miRNA, piRNA, snRNA, snoRNA, tRNA, and rRNA, with miRNA being the most abundant. A total of 351 different miRNAs were detected in plasma EVs, with the top 50 miRNAs accounting for 90% of all miRNA reads. miR-26a-5p was the most abundant miRNA, followed by miR-21-5p and miR-148-3p. qRT-PCR analysis showed that six miRNAs (miR-10a-5p, − 21-5p, −27b-3p, − 122-5p, −146a-5p, − 423-5p) were significantly increased in plasma EVs from HIV-positive compared to HIV-negative subjects in the validation cohort. Furthermore, miR-21-5p, −27b-3p, −146a-5p, and − 423-5p correlated positively with metabolite markers of oxidative stress and negatively with anti-inflammatory polyunsaturated fatty acids. Over-representation and pathway enrichment analyses of miRNAs and their target genes predicted functional association with oxidative stress responses, interferon gamma signaling, Toll-like receptor signaling, TGF beta signaling, and Notch signaling.

Conclusions

HIV-positive individuals on ART have increased abundance of circulating EVs carrying diverse small RNAs, with miRNAs being the most abundant. Several miRNAs associated with inflammation and oxidative stress are increased in circulating EVs of HIV-positive individuals, representing potential biomarkers of targetable pathways that contribute to disease pathogenesis.
Appendix
Available only for authorised users
Literature
1.
2.
Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.PubMedCrossRef
3.
d'Ettorre G, Paiardini M, Ceccarelli G, Silvestri G, Vullo V. HIV-associated immune activation: from bench to bedside. AIDS Res Hum Retrovir. 2011;27(4):355–64.PubMedCrossRef
4.
Suresh DR, Annam V, Pratibha K, Prasad BV. Total antioxidant capacity--a novel early bio-chemical marker of oxidative stress in HIV infected individuals. J Biomed Sci. 2009;16:61.PubMedPubMedCentralCrossRef
5.
Masia M, Padilla S, Fernandez M, Rodriguez C, Moreno A, Oteo JA, Antela A, Moreno S, Del Amo J, Gutierrez F, et al. Oxidative stress predicts all-cause mortality in HIV-infected patients. PLoS One. 2016;11(4):e0153456.PubMedPubMedCentralCrossRef
6.
Ivanov AV, Valuev-Elliston VT, Ivanova ON, Kochetkov SN, Starodubova ES, Bartosch B, Isaguliants MG. Oxidative stress during HIV infection: mechanisms and consequences. Oxidative Med Cell Longev. 2016;2016:8910396.CrossRef
7.
De Toro J, Herschlik L, Waldner C, Mongini C. Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front Immunol. 2015;6:203.PubMedPubMedCentralCrossRef
8.
Abels ER, Breakefield XO. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol. 2016;36(3):301–12.PubMedPubMedCentralCrossRef
9.
Yu X, Odenthal M, Fries JW. Exosomes as miRNA carriers: formation-function-future. Int J Mol Sci. 2016;17(12):2028.
10.
Kadiu I, Narayanasamy P, Dash PK, Zhang W, Gendelman HE. Biochemical and biologic characterization of exosomes and microvesicles as facilitators of HIV-1 infection in macrophages. J Immunol. 2012;189(2):744–54.PubMedCrossRef
11.
Hubert A, Subra C, Jenabian MA, Tremblay Labrecque PF, Tremblay C, Laffont B, Provost P, Routy JP, Gilbert C. Elevated abundance, size, and MicroRNA content of plasma extracellular vesicles in Viremic HIV-1+ patients: correlations with known markers of disease progression. J Acquir Immune Defic Syndr. 2015;70(3):219–27.PubMedPubMedCentralCrossRef
12.
Chettimada S, Lorenz DR, Misra V, Dillon ST, Reeves RK, Manickam C, Morgello S, Kirk GD, Mehta SH, Gabuzda D. Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy. Sci Rep. 2018;8(1):7227.PubMedPubMedCentralCrossRef
13.
Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y, Krogan NJ, Plemenitas A, Peterlin BM. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic. 2010;11(1):110–22.PubMedPubMedCentralCrossRef
14.
Fang Y, Wu N, Gan X, Yan W, Morrell JC, Gould SJ. Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol. 2007;5(6):e158.PubMedPubMedCentralCrossRef
15.
Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, Guendel I, Sampey G, Dalby E, Iglesias-Ussel M, et al. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. J Biol Chem. 2013;288(27):20014–33.PubMedPubMedCentralCrossRef
16.
Konadu KA, Chu J, Huang MB, Amancha PK, Armstrong W, Powell MD, Villinger F, Bond VC. Association of Cytokines with Exosomes in the plasma of HIV-1-seropositive individuals. J Infect Dis. 2015;211(11):1712–6.PubMedCrossRef
17.
Khatua AK, Taylor HE, Hildreth JE, Popik W. Exosomes packaging APOBEC3G confer human immunodeficiency virus resistance to recipient cells. J Virol. 2009;83(2):512–21.PubMedCrossRef
18.
Yao Z, Qiao Y, Li X, Chen J, Ding J, Bai L, Shen F, Shi B, Liu J, Peng L, et al. Exosomes exploit the virus entry machinery and pathway to transmit alpha interferon-induced antiviral activity. J Virol. 2018;92(24):01578–18.
19.
Boelens MC, Wu TJ, Nabet BY, Xu B, Qiu Y, Yoon T, Azzam DJ, Twyman-Saint Victor C, Wiemann BZ, Ishwaran H, et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell. 2014;159(3):499–513.PubMedPubMedCentralCrossRef
20.
Murray DD, Suzuki K, Law M, Trebicka J, Neuhaus Nordwall J, Johnson M, Vjecha MJ, Kelleher AD, Emery S. Circulating miR-122 and miR-200a as biomarkers for fatal liver disease in ART-treated, HIV-1-infected individuals. Sci Rep. 2017;7(1):10934.PubMedPubMedCentralCrossRef
21.
O'Meara T, Kong Y, Chiarella J, Price RW, Chaudhury R, Liu X, Spudich S, Robertson K, Emu B, Lu L. Exosomal MicroRNAs associate with neuropsychological performance in individuals with HIV infection on antiretroviral therapy. J Acquir Immune Defic Syndr. 2019;82(5):514–22.PubMedCrossRefPubMedCentral
22.
Rozowsky J, Kitchen RR, Park JJ, Galeev TR, Diao J, Warrell J, Thistlethwaite W, Subramanian SL, Milosavljevic A, Gerstein M. exceRpt: a comprehensive analytic platform for extracellular RNA profiling. Cell Syst. 2019;8(4):352–7 e353.PubMedPubMedCentralCrossRef
23.
24.
Piedade D, Azevedo-Pereira JM. MicroRNAs, HIV and HCV: a complex relation towards pathology. Rev Med Virol. 2016;26(3):197–215.PubMedCrossRef
25.
Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, Huang W, Squires K, Verlinghieri G, Zhang H. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med. 2007;13(10):1241–7.PubMedCrossRef
26.
Whisnant AW, Bogerd HP, Flores O, Ho P, Powers JG, Sharova N, Stevenson M, Chen CH, Cullen BR. In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms. MBio. 2013;4(2):e000193.PubMedCrossRef
27.
Parikh VN, Park J, Nikolic I, Channick R, Yu PB, De Marco T, Hsue PY, Chan SY. Brief report: coordinated modulation of circulating miR-21 in HIV, HIV-associated pulmonary arterial hypertension, and HIV/hepatitis C virus Coinfection. J Acquir Immune Defic Syndr. 2015;70(3):236–41.PubMedPubMedCentralCrossRef
28.
Hulsmans M, De Keyzer D, Holvoet P. MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis. FASEB J. 2011;25(8):2515–27.PubMedCrossRef
29.
Rastogi N, Gara RK, Trivedi R, Singh A, Dixit P, Maurya R, Duggal S, Bhatt ML, Singh S, Mishra DP. (6)-Gingerolinduced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression. Free Radic Biol Med. 2014;68:288–301.PubMedCrossRef
30.
Simionescu N, Niculescu LS, Sanda GM, Margina D, Sima AV. Analysis of circulating microRNAs that are specifically increased in hyperlipidemic and/or hyperglycemic sera. Mol Biol Rep. 2014;41(9):5765–73.PubMedCrossRef
31.
Engedal N, Zerovnik E, Rudov A, Galli F, Olivieri F, Procopio AD, Rippo MR, Monsurro V, Betti M, Albertini MC. From oxidative stress damage to pathways, networks, and autophagy via MicroRNAs. Oxidative Med Cell Longev. 2018;2018:4968321.CrossRef
32.
Neilsen CT, Goodall GJ, Bracken CP. IsomiRs--the overlooked repertoire in the dynamic microRNAome. Trends Genet. 2012;28(11):544–9.PubMedCrossRef
33.
Karimi N, Cvjetkovic A, Jang SC, Crescitelli R, Hosseinpour Feizi MA, Nieuwland R, Lotvall J, Lasser C. Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins. Cell Mol Life Sci. 2018;75(15):2873–86.PubMedPubMedCentralCrossRef
34.
Li L, Zhu D, Huang L, Zhang J, Bian Z, Chen X, Liu Y, Zhang CY, Zen K. Argonaute 2 complexes selectively protect the circulating microRNAs in cell-secreted microvesicles. PLoS One. 2012;7(10):e46957.PubMedPubMedCentralCrossRef
35.
Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13(4):423–33.PubMedPubMedCentralCrossRef
36.
Fuchs D, Forsman A, Hagberg L, Larsson M, Norkrans G, Reibnegger G, Werner ER, Wachter H. Immune activation and decreased tryptophan in patients with HIV-1 infection. J Interf Res. 1990;10(6):599–603.CrossRef
37.
Huengsberg M, Winer JB, Gompels M, Round R, Ross J, Shahmanesh M. Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients. Clin Chem. 1998;44(4):858–62.PubMedCrossRef
38.
Seymour CW, Yende S, Scott MJ, Pribis J, Mohney RP, Bell LN, Chen YF, Zuckerbraun BS, Bigbee WL, Yealy DM, et al. Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study. Intensive Care Med. 2013;39(8):1423–34.PubMedPubMedCentralCrossRef
39.
Kowalczyk-Pachel D, Iciek M, Wydra K, Nowak E, Gorny M, Filip M, Wlodek L, Lorenc-Koci E. Cysteine metabolism and oxidative processes in the rat liver and kidney after acute and repeated cocaine treatment. PLoS One. 2016;11(1):e0147238.PubMedPubMedCentralCrossRef
40.
Amorim MG, Valieris R, Drummond RD, Pizzi MP, Freitas VM, Sinigaglia-Coimbra R, Calin GA, Pasqualini R, Arap W, Silva IT, et al. A total transcriptome profiling method for plasma-derived extracellular vesicles: applications for liquid biopsies. Sci Rep. 2017;7(1):14395.PubMedPubMedCentralCrossRef
41.
Yuan T, Huang X, Woodcock M, Du M, Dittmar R, Wang Y, Tsai S, Kohli M, Boardman L, Patel T, et al. Plasma extracellular RNA profiles in healthy and cancer patients. Sci Rep. 2016;6:19413.PubMedPubMedCentralCrossRef
42.
El-Mogy M, Lam B, Haj-Ahmad TA, McGowan S, Yu D, Nosal L, Rghei N, Roberts P, Haj-Ahmad Y. Diversity and signature of small RNA in different bodily fluids using next generation sequencing. BMC Genomics. 2018;19(1):408.PubMedPubMedCentralCrossRef
43.
Franco S, Buccione D, Pluvinet R, Mothe B, Ruiz L, Nevot M, Jordan-Paiz A, Ramos L, Ausso S, Morillas RM, et al. Large-scale screening of circulating microRNAs in individuals with HIV-1 mono-infections reveals specific liver damage signatures. Antivir Res. 2018;155:106–14.PubMedCrossRef
44.
Bandiera S, Pfeffer S, Baumert TF, Zeisel MB. miR-122--a key factor and therapeutic target in liver disease. J Hepatol. 2015;62(2):448–57.PubMedCrossRef
45.
Chen AK, Sengupta P, Waki K, Van Engelenburg SB, Ochiya T, Ablan SD, Freed EO, Lippincott-Schwartz J. MicroRNA binding to the HIV-1 gag protein inhibits gag assembly and virus production. Proc Natl Acad Sci U S A. 2014;111(26):E2676–83.PubMedPubMedCentralCrossRef
46.
Castro FOF, Silva JM, Dorneles GP, Barros JBS, Ribeiro CB, Noronha I, Barbosa GR, Souza LCS, Guilarde AO, Pereira A, et al. Distinct inflammatory profiles in HIV-infected individuals under antiretroviral therapy using cannabis, cocaine or cannabis plus cocaine. AIDS. 2019;33(12):1831–42.PubMedCrossRef
47.
Cisneros IE, Erdenizmenli M, Cunningham KA, Paessler S, Dineley KT. Cocaine evokes a profile of oxidative stress and impacts innate antiviral response pathways in astrocytes. Neuropharmacology. 2018;135:431–43.PubMedPubMedCentralCrossRef
48.
Xiao J, Pan Y, Li XH, Yang XY, Feng YL, Tan HH, Jiang L, Feng J, Yu XY. Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4. Cell Death Dis. 2016;7(6):e2277.PubMedPubMedCentralCrossRef
49.
Thulasingam S, Massilamany C, Gangaplara A, Dai H, Yarbaeva S, Subramaniam S, Riethoven JJ, Eudy J, Lou M, Reddy J. miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells. Mol Cell Biochem. 2011;352(1–2):181–8.PubMedCrossRef
50.
Whisnant AW, Kehl T, Bao Q, Materniak M, Kuzmak J, Lochelt M, Cullen BR. Identification of novel, highly expressed retroviral microRNAs in cells infected by bovine foamy virus. J Virol. 2014;88(9):4679–86.PubMedPubMedCentralCrossRef
51.
Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006;103(33):12481–6.PubMedPubMedCentralCrossRef
52.
Pauley KM, Satoh M, Pauley BA, Dominguez-Gutierrez PR, Wallet SM, Holliday LS, Cha S, Reeves WH, Chan EK. Formation of GW/P bodies as marker for microRNA-mediated regulation of innate immune signaling in THP-1 cells. Immunol Cell Biol. 2010;88(2):205–12.PubMedCrossRef
53.
Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X. MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol. 2009;183(3):2150–8.PubMedCrossRef
54.
Geyer PE, Kulak NA, Pichler G, Holdt LM, Teupser D, Mann M. Plasma proteome profiling to assess human health and disease. Cell Syst. 2016;2(3):185–95.PubMedCrossRef
55.
56.
Petoumenos K, Law MG. Smoking, alcohol and illicit drug use effects on survival in HIV-positive persons. Curr Opin HIV AIDS. 2016;11(5):514–20.PubMedCrossRef
57.
Huang X, Yuan T, Tschannen M, Sun Z, Jacob H, Du M, Liang M, Dittmar RL, Liu Y, Liang M, et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics. 2013;14:319.PubMedPubMedCentralCrossRef
58.
59.
Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011;108(12):5003–8.PubMedPubMedCentralCrossRef
60.
61.
Tokar T, Pastrello C, Rossos AEM, Abovsky M, Hauschild AC, Tsay M, Lu R, Jurisica I. mirDIP 4.1-integrative database of human microRNA target predictions. Nucleic Acids Res. 2018;46(D1):D360–70.PubMedCrossRef
62.
63.
Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, Huang WC, Sun TH, Tu SJ, Lee WH, et al. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2018;46(D1):D296–302.PubMedCrossRef
64.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef
65.
Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091–3.PubMedPubMedCentralCrossRef
Metadata
Title
Small RNA sequencing of extracellular vesicles identifies circulating miRNAs related to inflammation and oxidative stress in HIV patients
Authors
Sukrutha Chettimada
David R. Lorenz
Vikas Misra
Steven M. Wolinsky
Dana Gabuzda
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2020
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-020-00386-5

Other articles of this Issue 1/2020

BMC Immunology 1/2020 Go to the issue

Research article

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

Correction

Correction to: Ionizing radiation modulates the phenotype and function of human CD4+ induced regulatory T cells

Research article

miR32-5p promoted vascular smooth muscle cell calcification by upregulating TNFα in the microenvironment

Research article

Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease

Research article

Prognostic role of red blood cell distribution width in patients with sepsis: a systematic review and meta-analysis

Research article

A combination of the activation marker CD86 and the immune checkpoint marker B and T lymphocyte attenuator (BTLA) indicates a putative permissive activation state of B cell subtypes in healthy blood donors independent of age and sex
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