Abstract
We previously reported serum C-reactive protein (CRP) elevation after acute myocardial infarction (MI) to be associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling, and cardiac death. Experimental studies have indicated that CRP per se has various biological actions including proinflammatory and proapoptotic effects, suggesting a pathogenic role of CRP in the post-MI remodeling process. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI via deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their transgene-negative littermates (control) underwent left coronary artery ligation. There was no apparent difference in phenotypic features between CRP-Tg and control mice before MI. Although mortality and infarct size were similar in the two groups, CRP-Tg mice showed more LV dilation and worse LV function with more prominent cardiomyocyte hypertrophy and fibrosis in the noninfarcted regions after MI than controls. Histological evaluation conducted 1 wk post-MI revealed a higher rate of apoptosis and more macrophage infiltration in the border zones of infarcted hearts from CRP-Tg mice in relation to increased monocyte chemotactic protein (MCP)-1 expression and matrix metalloproteinase (MMP)-9 activity. Increased CRP expression exacerbates LV dysfunction and promotes adverse LV remodeling after MI in mice. The deleterious effect of CRP on post-MI LV remodeling may be associated with increased apoptotic rates, macrophage infiltration, MCP-1 expression, and MMP-9 activity in the border zone.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 299 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2010 Dec |
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Keywords
- Apoptosis
- Macrophage
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
- Cardiology and Cardiovascular Medicine
Cite this
Increased C-reactive protein expression exacerbates left ventricular dysfunction and remodeling after myocardial infarction. / Takahashi, Toshiyuki; Anzai, Toshihisa; Kaneko, Hidehiro; Mano, Yoshinori; Anzai, Atsushi; Nagai, Toshiyuki; Kohno, Takashi; Maekawa, Yuichiro; Yoshikawa, Tsutomu; Fukuda, Keiichi; Ogawa, Satoshi.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 299, No. 6, 12.2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased C-reactive protein expression exacerbates left ventricular dysfunction and remodeling after myocardial infarction
AU - Takahashi, Toshiyuki
AU - Anzai, Toshihisa
AU - Kaneko, Hidehiro
AU - Mano, Yoshinori
AU - Anzai, Atsushi
AU - Nagai, Toshiyuki
AU - Kohno, Takashi
AU - Maekawa, Yuichiro
AU - Yoshikawa, Tsutomu
AU - Fukuda, Keiichi
AU - Ogawa, Satoshi
PY - 2010/12
Y1 - 2010/12
N2 - We previously reported serum C-reactive protein (CRP) elevation after acute myocardial infarction (MI) to be associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling, and cardiac death. Experimental studies have indicated that CRP per se has various biological actions including proinflammatory and proapoptotic effects, suggesting a pathogenic role of CRP in the post-MI remodeling process. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI via deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their transgene-negative littermates (control) underwent left coronary artery ligation. There was no apparent difference in phenotypic features between CRP-Tg and control mice before MI. Although mortality and infarct size were similar in the two groups, CRP-Tg mice showed more LV dilation and worse LV function with more prominent cardiomyocyte hypertrophy and fibrosis in the noninfarcted regions after MI than controls. Histological evaluation conducted 1 wk post-MI revealed a higher rate of apoptosis and more macrophage infiltration in the border zones of infarcted hearts from CRP-Tg mice in relation to increased monocyte chemotactic protein (MCP)-1 expression and matrix metalloproteinase (MMP)-9 activity. Increased CRP expression exacerbates LV dysfunction and promotes adverse LV remodeling after MI in mice. The deleterious effect of CRP on post-MI LV remodeling may be associated with increased apoptotic rates, macrophage infiltration, MCP-1 expression, and MMP-9 activity in the border zone.
AB - We previously reported serum C-reactive protein (CRP) elevation after acute myocardial infarction (MI) to be associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling, and cardiac death. Experimental studies have indicated that CRP per se has various biological actions including proinflammatory and proapoptotic effects, suggesting a pathogenic role of CRP in the post-MI remodeling process. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI via deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their transgene-negative littermates (control) underwent left coronary artery ligation. There was no apparent difference in phenotypic features between CRP-Tg and control mice before MI. Although mortality and infarct size were similar in the two groups, CRP-Tg mice showed more LV dilation and worse LV function with more prominent cardiomyocyte hypertrophy and fibrosis in the noninfarcted regions after MI than controls. Histological evaluation conducted 1 wk post-MI revealed a higher rate of apoptosis and more macrophage infiltration in the border zones of infarcted hearts from CRP-Tg mice in relation to increased monocyte chemotactic protein (MCP)-1 expression and matrix metalloproteinase (MMP)-9 activity. Increased CRP expression exacerbates LV dysfunction and promotes adverse LV remodeling after MI in mice. The deleterious effect of CRP on post-MI LV remodeling may be associated with increased apoptotic rates, macrophage infiltration, MCP-1 expression, and MMP-9 activity in the border zone.
KW - Apoptosis
KW - Macrophage
UR - http://www.scopus.com/inward/record.url?scp=78649735144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649735144&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00001.2010
DO - 10.1152/ajpheart.00001.2010
M3 - Article
C2 - 20852043
AN - SCOPUS:78649735144
VL - 299
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 6
ER -