Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25550440
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Circ+Heart+Fail
2015 ; 8
(2
): 352-61
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Tumor necrosis factor: a mechanistic link between angiotensin-II-induced cardiac
inflammation and fibrosis
#MMPMID25550440
Duerrschmid C
; Trial J
; Wang Y
; Entman ML
; Haudek SB
Circ Heart Fail
2015[Mar]; 8
(2
): 352-61
PMID25550440
show ga
BACKGROUND: Continuous angiotensin-II infusion induced the uptake of monocytic
fibroblast precursors that initiated the development of cardiac fibrosis; these
cells and concurrent fibrosis were absent in mice lacking tumor necrosis factor
receptor 1 (TNFR1). We now investigated their cellular origin and temporal uptake
and the involvement of TNFR1 in monocyte-to-fibroblast differentiation. METHODS
AND RESULTS: Within a day, angiotensin-II induced a proinflammatory environment
characterized by production of inflammatory chemokines, cytokines, and
TH1-interleukins and uptake of bone marrow-derived M1 cells. After a week, the
cardiac environment changed to profibrotic with growth factor and TH2-interleukin
synthesis, uptake of bone marrow-derived M2 cells, and the presence of M2-related
fibroblasts. TNFR1 signaling was not necessary for early M1 uptake, but its
absence diminished the amount of M2 cells. TNFR1-knockout hearts also showed
reduced levels of cytokine expression, but not of TH-related lymphokines.
Reconstitution of wild-type bone marrow into TNFR1-knockout mice was sufficient
to restore M2 uptake, upregulation of proinflammatory and profibrotic genes, and
development of fibrosis in response to angiotensin-II. We also developed an in
vitro mouse monocyte-to-fibroblast maturation assay that confirmed the essential
role of TNFR1 in the sequential progression of monocyte activation and fibroblast
formation. CONCLUSIONS: Development of cardiac fibrosis in response to
angiotensin-II was mediated by myeloid precursors and consisted of 2 stages. A
primary M1 inflammatory response was followed by a subsequent M2 fibrotic
response. Although the first phase seemed to be independent of TNFR1 signaling,
the later phase (and development of fibrosis) was abrogated by deletion of TNFR1.
|Angiotensin II/*immunology
[MESH]
|Animals
[MESH]
|Cell Migration Assays
[MESH]
|Female
[MESH]
|Fibroblasts/metabolism
[MESH]
|Fibrosis
[MESH]
|Inflammation Mediators/metabolism
[MESH]
|Male
[MESH]
|Mice, Inbred C57BL
[MESH]
|Mice, Knockout
[MESH]
|Myocardium/immunology/*pathology
[MESH]
|Myocytes, Cardiac/*immunology/pathology
[MESH]
|Receptors, Tumor Necrosis Factor, Type I/metabolism/*physiology
[MESH]
free
free
free
