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Complement Destabilizes Cardiomyocyte Function In Vivo after Polymicrobial Sepsis and In Vitro.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Sep 15; Vol. 197 (6), pp. 2353-61. Date of Electronic Publication: 2016 Aug 12. - Publication Year :
- 2016
-
Abstract
- There is accumulating evidence during sepsis that cardiomyocyte (CM) homeostasis is compromised, resulting in cardiac dysfunction. An important role for complement in these outcomes is now demonstrated. Addition of C5a to electrically paced CMs caused prolonged elevations of intracellular Ca(2+) concentrations during diastole, together with the appearance of spontaneous Ca(2+) transients. In polymicrobial sepsis in mice, we found that three key homeostasis-regulating proteins in CMs were reduced: Na(+)/K(+)-ATPase, which is vital for effective action potentials in CMs, and two intracellular Ca(2+) concentration regulatory proteins, that is, sarcoplasmic/endoplasmic reticulum calcium ATPase 2 and the Na(+)/Ca(2+) exchanger. Sepsis caused reduced mRNA levels and reductions in protein concentrations in CMs for all three proteins. The absence of either C5a receptor mitigated sepsis-induced reductions in the three regulatory proteins. Absence of either C5a receptor (C5aR1 or C5aR2) diminished development of defective systolic and diastolic echocardiographic/Doppler parameters developing in the heart (cardiac output, left ventricular stroke volume, isovolumic relaxation, E' septal annulus, E/E' septal annulus, left ventricular diastolic volume). We also found in CMs from septic mice the presence of defective current densities for Ik1, l-type calcium channel, and Na(+)/Ca(2+) exchanger. These defects were accentuated in the copresence of C5a. These data suggest complement-related mechanisms responsible for development of cardiac dysfunction during sepsis.<br />Competing Interests: The authors declare no commercial or financial conflicts of interest related to the studies.<br /> (Copyright © 2016 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Calcium metabolism
Calcium Channels, L-Type immunology
Coinfection microbiology
Coinfection physiopathology
Complement C5a immunology
Cytoplasm chemistry
Cytoplasm metabolism
Heart physiopathology
Mice
Myocytes, Cardiac microbiology
Receptor, Anaphylatoxin C5a deficiency
Receptor, Anaphylatoxin C5a immunology
Receptor, Anaphylatoxin C5a physiology
Sarcoplasmic Reticulum Calcium-Transporting ATPases immunology
Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism
Sepsis complications
Coinfection immunology
Myocytes, Cardiac immunology
Myocytes, Cardiac pathology
Sepsis immunology
Sepsis physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 197
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 27521340
- Full Text :
- https://doi.org/10.4049/jimmunol.1600091