Cardiac side effects of RNA-based SARS-CoV-2 vaccines : Hidden cardiotoxic effects of mRNA-1273 and BNT162b2 on ventricular myocyte function and structure
© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..
BACKGROUND AND PURPOSE: To protect against SARS-CoV-2 infection, the first mRNA-based vaccines, Spikevax (mRNA-1273, Moderna) and Comirnaty (BNT162b2, Pfizer/Biontech), were approved in 2020. The structure and assembly of the immunogen-in both cases, the SARS-CoV-2 spike (S) glycoprotein-are determined by a messenger RNA sequence that is translated by endogenous ribosomes. Cardiac side-effects, which for the most part can be classified by their clinical symptoms as myo- and/or pericarditis, can be caused by both mRNA-1273 and BNT162b2.
EXPERIMENTAL APPROACH: As persuasive theories for the underlying pathomechanisms have yet to be developed, this study investigated the effect of mRNA-1273 and BNT162b2 on the function, structure, and viability of isolated adult rat cardiomyocytes over a 72 h period.
KEY RESULTS: In the first 24 h after application, both mRNA-1273 and BNT162b2 caused neither functional disturbances nor morphological abnormalities. After 48 h, expression of the encoded spike protein was detected in ventricular cardiomyocytes for both mRNAs. At this point in time, mRNA-1273 induced arrhythmic as well as completely irregular contractions associated with irregular as well as localized calcium transients, which provide indications of significant dysfunction of the cardiac ryanodine receptor (RyR2). In contrast, BNT162b2 increased cardiomyocyte contraction via significantly increased protein kinase A (PKA) activity at the cellular level.
CONCLUSION AND IMPLICATIONS: Here, we demonstrated for the first time, that in isolated cardiomyocytes, both mRNA-1273 and BNT162b2 induce specific dysfunctions that correlate pathophysiologically to cardiomyopathy. Both RyR2 impairment and sustained PKA activation may significantly increase the risk of acute cardiac events.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:181 |
|---|---|
| Enthalten in: |
British journal of pharmacology - 181(2024), 3 vom: 25. Feb., Seite 345-361 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Schreckenberg, Rolf [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 15.01.2024 Date Revised 06.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/bph.16262 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363216073 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363216073 | ||
| 003 | DE-627 | ||
| 005 | 20240307232024.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/bph.16262 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1319.xml |
| 035 | |a (DE-627)NLM363216073 | ||
| 035 | |a (NLM)37828636 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Schreckenberg, Rolf |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cardiac side effects of RNA-based SARS-CoV-2 vaccines |b Hidden cardiotoxic effects of mRNA-1273 and BNT162b2 on ventricular myocyte function and structure |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.01.2024 | ||
| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. | ||
| 520 | |a BACKGROUND AND PURPOSE: To protect against SARS-CoV-2 infection, the first mRNA-based vaccines, Spikevax (mRNA-1273, Moderna) and Comirnaty (BNT162b2, Pfizer/Biontech), were approved in 2020. The structure and assembly of the immunogen-in both cases, the SARS-CoV-2 spike (S) glycoprotein-are determined by a messenger RNA sequence that is translated by endogenous ribosomes. Cardiac side-effects, which for the most part can be classified by their clinical symptoms as myo- and/or pericarditis, can be caused by both mRNA-1273 and BNT162b2 | ||
| 520 | |a EXPERIMENTAL APPROACH: As persuasive theories for the underlying pathomechanisms have yet to be developed, this study investigated the effect of mRNA-1273 and BNT162b2 on the function, structure, and viability of isolated adult rat cardiomyocytes over a 72 h period | ||
| 520 | |a KEY RESULTS: In the first 24 h after application, both mRNA-1273 and BNT162b2 caused neither functional disturbances nor morphological abnormalities. After 48 h, expression of the encoded spike protein was detected in ventricular cardiomyocytes for both mRNAs. At this point in time, mRNA-1273 induced arrhythmic as well as completely irregular contractions associated with irregular as well as localized calcium transients, which provide indications of significant dysfunction of the cardiac ryanodine receptor (RyR2). In contrast, BNT162b2 increased cardiomyocyte contraction via significantly increased protein kinase A (PKA) activity at the cellular level | ||
| 520 | |a CONCLUSION AND IMPLICATIONS: Here, we demonstrated for the first time, that in isolated cardiomyocytes, both mRNA-1273 and BNT162b2 induce specific dysfunctions that correlate pathophysiologically to cardiomyopathy. Both RyR2 impairment and sustained PKA activation may significantly increase the risk of acute cardiac events | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BNT162b2 | |
| 650 | 4 | |a SARS-CoV-2 spike (S) glycoprotein | |
| 650 | 4 | |a cardiac dysfunction | |
| 650 | 4 | |a cardiac side effects | |
| 650 | 4 | |a mRNA-1273 | |
| 650 | 4 | |a protein kinase A (PKA) | |
| 650 | 4 | |a ryanodine receptor (RyR2) | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a BNT162 Vaccine |2 NLM | |
| 650 | 7 | |a 2019-nCoV Vaccine mRNA-1273 |2 NLM | |
| 650 | 7 | |a EPK39PL4R4 |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 650 | 7 | |a Ryanodine Receptor Calcium Release Channel |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Woitasky, Nadine |e verfasserin |4 aut | |
| 700 | 1 | |a Itani, Nadja |e verfasserin |4 aut | |
| 700 | 1 | |a Czech, Laureen |e verfasserin |4 aut | |
| 700 | 1 | |a Ferdinandy, Péter |e verfasserin |4 aut | |
| 700 | 1 | |a Schulz, Rainer |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of pharmacology |d 1968 |g 181(2024), 3 vom: 25. Feb., Seite 345-361 |w (DE-627)NLM000001325 |x 1476-5381 |7 nnns |
| 773 | 1 | 8 | |g volume:181 |g year:2024 |g number:3 |g day:25 |g month:02 |g pages:345-361 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/bph.16262 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 181 |j 2024 |e 3 |b 25 |c 02 |h 345-361 | ||