Myocarditis/Pericarditis

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Myocarditis/Pericarditis

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Myocarditis/Pericarditis
© 2021 PFPC

Myocarditis is inflammation of the heart muscle, and pericarditis is inflammation of the outer lining of the heart. Myopericarditis is a combination of both. (Pericarditis with concurrent mild myocardial involvement, documented by elevation of biomarkers of myocardial damage, such as increased C-reactive protein (CRP), troponins, IL-6, TNF-α, VCAM-1, etc.).

Myocarditis has been observed in children suffering from COVID-19 (de Cevins et al., 2021; Erol et al., 2021) as well as after vaccinations with Pfizer/Moderna vaccines (Verma et al., 2021; Kim et al., 2021; Montgomery et al., 2021; Koizumi et al., 2021). It develops often in young, seemingly healthy men.

A recent study with a mouse model has shown that myopericarditis can be produced consistently with intravenous (IV) injection of the mRNA vaccines. A second dose - given either as IV or intramuscular (IM) injection, further aggravated the condition (Li et al., 2021).

COVID-19
  • de Cevins C, Luka M, Smith N, et al. - "A monocyte/dendritic cell molecular signature of SARS-CoV-2 related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis" Med (N Y). 2021 Aug 14. doi: 10.1016/j.medj.2021.08.002. Epub ahead of print. PMID: 34414385; PMCID: PMC8363470.
    https://pubmed.ncbi.nlm.nih.gov/34414385/

    Erol N, Alpinar A, Erol C, Sari E, Alkan K - "Intriguing New Faces Of Covid-19: Persisting Clinical Symptoms And Cardiac Effects in Children" Cardiol Young. 2021 Aug 19:1-27. doi: 10.1017/S1047951121003693. Epub ahead of print. PMID: 34407902.
    https://pubmed.ncbi.nlm.nih.gov/34407902/

mRNA Vaccines
  • Verma AK, Lavine KJ, Lin CY - "Myocarditis after Covid-19 mRNA Vaccination" N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMc2109975. Epub ahead of print. PMID: 34407340.
    https://www.nejm.org/doi/10.1056/NEJMc2 ... %200pubmed

    Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN, Parker MA, Kim RJ - "Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination" JAMA Cardiol. 2021 Jun 29:e212828. doi: 10.1001/jamacardio.2021.2828. Epub ahead of print. PMID: 34185046; PMCID: PMC8243258.
    https://jamanetwork.com/journals/jamaca ... le/2781602

    Li C, Chen Y, Zhao Y, Lung DC, Ye Z, Song W, Liu FF, Cai JP, Wong WM, Yip CC, Chan JF, To KK, Sridhar S, Hung IF, Chu H, Kok KH, Jin DY, Zhang AJ, Yuen KY - " Intravenous injection of COVID-19 mRNA vaccine can induce acute myopericarditis in mouse model" Clin Infect Dis. 2021 Aug 18:ciab707. doi: 10.1093/cid/ciab707. Epub ahead of print. PMID: 34406358.
    https://academic.oup.com/cid/advance-ar ... 07/6353927
    "The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose."

    Ioannou A - "Myocarditis should be considered in those with a troponin rise and unobstructed coronary arteries following Pfizer-BioNTech COVID-19 vaccination" QJM. 2021 Aug 31:hcab231
    https://pubmed.ncbi.nlm.nih.gov/34463755/

    Khogali F, Abdelrahman R - "Unusual Presentation of Acute Perimyocarditis Following SARS-COV-2 mRNA-1237 Moderna Vaccination" Cureus. 2021 Jul 23;13(7):e16590. doi: 10.7759/cureus.16590. PMID: 34447639; PMCID: PMC8381757.\
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381757/

    Viskin D, Topilsky Y, Aviram G, Mann T, Sadon S, Hadad Y, Flint N, Shmilovich H, Banai S, Havakuk O - "Myocarditis Associated With COVID-19 Vaccination: Echocardiography, Cardiac Tomography, and Magnetic Resonance Imaging Findings" Circ Cardiovasc Imaging. 2021 Aug 25:CIRCIMAGING121013236. doi: 10.1161/CIRCIMAGING.121.013236. Epub ahead of print. PMID: 34428917
    https://www.ahajournals.org/doi/10.1161 ... %200pubmed

    Montgomery J, Ryan M, Engler R, Hoffman D, McClenathan B, Collins L, Loran D, Hrncir D, Herring K, Platzer M, Adams N, Sanou A, Cooper LT Jr. - "Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military" JAMA Cardiol. 2021 Jun 29:e212833. doi: 10.1001/jamacardio.2021.2833. Epub ahead of print. PMID: 34185045; PMCID: PMC8243257.
    https://pubmed.ncbi.nlm.nih.gov/34185045/

    Koizumi T, Awaya T, Yoshioka K, Kitano S, Hayama H, Amemiya K, Enomoto Y, Yazaki Y, Moroi M, Nakamura M - "Myocarditis after COVID-19 mRNA vaccines" QJM. 2021 Sep 21:hcab244. doi: 10.1093/qjmed/hcab244. Epub ahead of print. PMID: 34546329.
https://pubmed.ncbi.nlm.nih.gov/34546329/

Fluoride

Myocarditis has been observed in fluorosis and after organic fluoride poisoning (Ma et al., 2019).
  • Ma Z, Peng JM, Zhu ZL, Chen ML, Cai MW, Zuo JB, Zhuang XZ - "Characteristic analysis of organic fluorosis caused by applying of touch screen anti-fingerprint nanocoating material" Chinese Journal of Industrial Hygiene and Occupational Diseases 37(12):921-925 (2019) Chinese
    https://pubmed.ncbi.nlm.nih.gov/31937034/

    Quadri JA, Sarwar S, Pinky, Kar P, Singh S, Mallick SR, Arava S, Nag TC, Roy TS, Shariff A - "Fluoride induced tissue hypercalcemia, IL-17 mediated inflammation and apoptosis lead to cardiomyopathy: Ultrastructural and biochemical findings" Toxicology 406-407:44-57 (2018)
    https://pubmed.ncbi.nlm.nih.gov/29800585/

    Wang HW, Liu J, Zhao J, Lin L, Zhao WP, Tan PP, Tian WS, Zhou BH - "Ca2+ metabolic disorder and abnormal expression of cardiac troponin involved in fluoride-induced cardiomyocyte damage" Chemosphere 201:564-570 (2018)
    https://pubmed.ncbi.nlm.nih.gov/29533806/?dopt=Abstract

Thyroid

Low FT3, commonly observed in COVID-19 and identified as a biomarker for disease mortality and severity, increases the risk of adverse cardiovascular events in adult patients with acute viral myocarditis (Zhao et al., 2019). Myocarditis is also observed in autoimmune thyroid disease (Wu et al., 2021; Lorin et al., 2003).
  • Zhao Y, Wang WY, Tian J, Zhang X, Yang M, Chen J, Mu M, Tang YD - "Impact of low T3 syndrome on adverse cardiovascular events in adult patients with acute viral myocarditis" Zhonghua Xin Xue Guan Bing Za Zhi 47(6):447-451 (2019) Chinese. doi: 10.3760/cma.j.issn.0253-3758.2019.06.005. PMID: 31262128.
    https://pubmed.ncbi.nlm.nih.gov/31262128/

    Fu MY, Wang QW, Xue Y, Xu F, Li CL, An XJ - "Relevant researches on chronic viral myocarditis (CVMC) in children, complicated with arrhythmia and thyroid hormone level" Eur Rev Med Pharmacol Sci 21(13):3083-3087 (2017)
    https://www.europeanreview.org/article/10893

    Wu L, Wang W, Leng Q, Tang N, Zhou N, Wang Y, Wang DW - "Focus on Autoimmune Myocarditis in Graves' Disease: A Case-Based Review" Front Cardiovasc Med 8:678645 (2021)
    https://pubmed.ncbi.nlm.nih.gov/34307494/

    Lorin De La Grandmaison G, Izembart M, Fornes P, Paraire F - "Myocarditis associated with Hashimoto's disease: a case report" Int J Legal Med 117(6):361-4 (2003)
    https://pubmed.ncbi.nlm.nih.gov/14520579/

Gq/11

Pathways activated by Gq/11 are well established as the major pathways involved in myocardial hypertrophy.
  • Tinker A, Finlay M, Nobles M, Opel A - "The contribution of pathways initiated via the Gq\11 G-protein family to atrial fibrillation" Pharmacol Res 105:54-61 (2016)
    https://pubmed.ncbi.nlm.nih.gov/26773203/

    Reuter H, Seuthe K, Korkmaz Y, Grönke S, Hoyer DP, Rottlaender D, Zobel C, Addicks K, Hoyer J, Grimminger P, Brabender J, Wilkie TM, Erdmann E - "The G protein Gα11 is essential for hypertrophic signalling in diabetic myocardium" Int J Cardiol 167(4):1476-85 (2013)
    https://linkinghub.elsevier.com/retriev ... 12)00460-3

    Wettschureck N, Rütten H, Zywietz A, Gehring D, Wilkie TM, Chen J, Chien KR, Offermanns S - "Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes" Nat Med 7(11):1236-40 (2001)
    https://pubmed.ncbi.nlm.nih.gov/11689889/

    Park-Windhol C, Zhang P, Zhu M, Su J, Chaves L Jr, Maldonado AE, King ME, Rickey L, Cullen D, Mende U - "Gq/11-mediated signaling and hypertrophy in mice with cardiac-specific transgenic expression of regulator of G-protein signaling 2" PLoS One 7(7):e40048 (2012)
    https://pubmed.ncbi.nlm.nih.gov/22802950/
    "Activation of Gq/11-mediated signaling is required for pressure overload-induced cardiomyocyte (CM) hypertrophy to develop."

    Wolf S, Abd Alla J, Quitterer U - "Sensitization of the Angiotensin II AT1 Receptor Contributes to RKIP-Induced Symptoms of Heart Failure" Front Med (Lausanne) 5:359 (2019) doi: 10.3389/fmed.2018.00359. PMID: 30687708; PMCID: PMC6333672
    https://pubmed.ncbi.nlm.nih.gov/30687708/

    Mende U, Kagen A, Cohen A, Aramburu J, Schoen FJ, Neer EJ - "Transient cardiac expression of constitutively active Galphaq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways" Proc Natl Acad Sci U S A 95(23):13893-8 (1998) doi: 10.1073/pnas.95.23.13893. PMID: 9811897; PMCID: PMC24952.
"We now report that transient, modest expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the Gq alpha subunit (HAalpha*q) in hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after the initiating stimulus becomes undetectable. At 2 weeks, HAalpha*q protein is expressed at less than 50% of endogenous alphaq/11, and the transgenic hearts are essentially normal morphologically. Although HAalpha*q protein declines at 4 weeks and is undetectable by 10 weeks, the animals develop cardiac hypertrophy and dilatation and die between 8 and 30 weeks in heart failure. As the pathology develops, endogenous alphaq/11 rises (2.9-fold in atria; 1.8-fold in ventricles). At 2 weeks, basal PLC activity is increased 9- to 10-fold in atria but not ventricles. By 10 weeks, it is elevated in both, presumably because of the rise in endogenous alphaq/11. "
SEE ALSO:

Cardiac troponins. viewtopic.php?f=66&t=1883
IL6. viewtopic.php?f=66&t=1885
TNF. viewtopic.php?f=66&t=1895
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