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Human Heart Generates Complement Proteins That Are Upregulated and Activated After Myocardial Infarction
Open accessAbstract
Abstract —In human heart, we detected mRNAs and proteins for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 with the use of reverse transcriptase–polymerase chain reaction, Western blotting, and immunohistochemical techniques. We found an upregulation of both mRNAs and proteins in areas of recent and old myocardial infarctions. In both situations, the classical complement pathway was activated, with C4d, C3d, and the membrane attack complex (C5b-9) being deposited on damaged cardiac myocytes. These activated complement components were also identified on Western blots of infarcted tissue. Complement mRNAs in infarcted heart tissue were higher than those in liver, and liver complement mRNAs were not upregulated in cases with infarcted hearts. Our results establish that (1) complement proteins are endogenously produced by human heart; (2) the classical complement pathway is fully activated after myocardial infarction; (3) complement activation is directly involved in myocardial damage after ischemic insults; and (4) damage from complement activation may be chronically sustained. These data suggest that inhibition of the complement system should be effective in treating myocardial infarction.
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MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287
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Cited by
Raedschelders, K., Ansley, D. M., & Chen, D. D. Y. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.11.004 · Cited by 388
Mechanisms of myocardial reperfusion injury
Park, J. L., & Lucchesi, B. R. (1999) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(99)01073-5 · Cited by 337
The Mechanistic Basis of Infarct Healing
Frangogiannis, N. G. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.1907 · Cited by 288
Anti‐inflammatory therapies in myocardial infarction: failures, hopes and challenges
Huang, S., & Frangogiannis, N. G. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14155 · Cited by 282
Local Neuroinflammation and the Progression of Alzheimer's Disease
McGeer, P. L., & McGeer, E. G. (2002) · Journal of Neurovirology · doi:10.1080/13550280290100969 · Cited by 255
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Metadata
- Authors
- Yasojima, K., Schwab, C., McGeer, E. G., & McGeer, P. L.
- Venue
- Circulation Research
- Published
- 1998-10-19
- Volume
- 83
- Issue
- 8
- Pages
- 860-869
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2146103737
- Cited by
- 161
- References
- 1
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yasojima, K., Schwab, C., McGeer, E. G., & McGeer, P. L. (1998). Human Heart Generates Complement Proteins That Are Upregulated and Activated After Myocardial Infarction. Circulation Research. https://doi.org/10.1161/01.res.83.8.860
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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