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Complement component C3 and the TLR co-receptor CD14 are not involved in angiotensin II induced cardiac remodelling
Negar Shahini1, Camilla Schjalm2, Per H Nilsson3
1Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.
Insights
Complement component 3 (C3) and Toll-like receptor (TLR) co-receptor CD14 do not impact cardiac remodelling. Studies show C3 and CD14 deficiency did not alter cardiac structure or fibrosis after pressure overload.
Area of Science:
- Immunology
- Cardiovascular Biology
- Innate Immunity
Background:
- Inflammation drives cardiac hypertrophy and remodelling.
- The complement system and Toll-like receptors (TLRs) are implicated in cardiac remodelling.
- The specific roles of complement component 3 (C3) and TLR co-receptor CD14 in pressure overload-induced cardiac remodelling remain unclear.
Purpose of the Study:
- To investigate the involvement of C3, CD14, and their synergy in angiotensin II-induced cardiac hypertrophy and remodelling.
- To determine if C3 and CD14 influence cardiac structure, function, fibrosis, and inflammatory responses under pressure overload.
Main Methods:
- Utilized male C57Bl/6J mice genetically deficient in C3, CD14, or both (C3CD14), alongside wild-type (WT) controls.
- Administered angiotensin II infusion for 7 days to induce pressure overload and cardiac hypertrophy.
- Assessed cardiac structure, function, fibrosis, blood pressure, and inflammatory markers (IL-6, C5a, Mac2).
Main Results:
- Angiotensin II induced mild cardiac hypertrophy and fibrosis in WT mice.
- No significant differences in systolic blood pressure, cardiac function, cardiac structure, or fibrosis were observed between WT mice and C3, CD14, or C3CD14 deficient mice.
- While IL-6 levels were comparable in C3-deficient mice, they were decreased in CD14 and C3CD14 deficient mice, suggesting a partial role for CD14 in the inflammatory response.
Conclusions:
- Deficiency in C3, CD14, or both did not affect cardiac remodelling following angiotensin II-induced pressure overload.
- These findings suggest that C3 and CD14 are not critical mediators of angiotensin II-induced adverse cardiac remodelling.
- The study indicates that the innate immune components C3 and CD14 may not play a significant role in this specific model of cardiac pressure overload.
Abstract:
Inflammation is centrally involved in the development of cardiac hypertrophy and the processes of remodelling. The complement system and Toll-like receptor (TLR) family, two upstream arms of the innate immune system, have previously been reported to be involved in cardiac remodelling. However, the role of complement component 3 (C3), TLR co-receptor CD14 and the synergy between them have not been addressed during pressure overload-induced cardiac remodelling. Here, we examined angiotensin II-induced cardiac hypertrophy and remodelling for 7 days in male C57Bl/6 J mice deficient in C3, CD14, or both (C3CD14), and WT controls. Angiotensin II infusion induced a mild concentric hypertrophic phenotype in WT mice with increased left ventricle weight, wall thicknesses and reduced ventricular internal diameter, associated with increased cardiac fibrosis. However, there were no differences between WT mice and mice deficient for C3, CD14 or C3CD14, as systolic blood pressure, cardiac function and structure and levels of fibrosis were comparable between WT mice and the three other genotypes. C5a did not change in angiotensin II treated mice, whereas Mac2 levels were increased in angiotensin II treated mice, but did not differ between genotypes. The inflammatory IL-6 response was comparable between WT and C3 deficient mice, however, it was decreased in CD14 and C3CD14 deficient mice. We conclude that deficiency in C3, CD14 or C3CD14 had no effect on cardiac remodelling following angiotensin II-induced pressure overload. This suggests that C3 and CD14 are not involved in angiotensin II-induced adverse cardiac remodelling.
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