PMID- 18320471
OWN - NLM
STAT- MEDLINE
DCOM- 20080416
LR  - 20080305
IS  - 1532-2297 (Electronic)
IS  - 1082-6068 (Linking)
VI  - 38
IP  - 2
DP  - 2008
TI  - Mechanical stretch induced interleukin-18 (IL-18) expression through Angiotensin 
      subtype 1 receptor (AT1R) and endothelin-1 in cardiomyocytes.
PG  - 201-12
LID - 10.1080/10826060701885704 [doi]
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine with multiple biological 
      functions. We and others have demonstrated that an increased level of circulating 
      IL-18 is one of the risk factors for cardiovascular diseases. Endothelin-1 (ET-1) 
      has been reported to be a potent hypertrophy-promoting factor through RhoA and 
      Rho-Kinase. Mechanical stretch induces a hypertrophic response, partly through 
      the production of ET-1 through Endothelin A receptor (ETAR). Moreover, it has 
      also been reported that mechanical stretch induces cardiac hypertrophy through 
      Angiotensin subtype 1 receptor (AT1R). However, the mechanism by which the IL-18 
      gene expression is regulated in cardiomyocytes has not yet been fully understood. 
      This study was designed to elucidate the functional significance of IL-18 gene 
      expression in response to mechanical stretch. Neonatal rat cardiomyocytes 
      cultured on silicone dishes were subjected to stretch. The moderate 20% 
      mechanical stretch resulted in the elevation of IL-18 expression in a 
      time-dependent manner with the maximal level achieved 36 hours after the stretch. 
      Olmesartan, AT1R antagonist inhibited stretch-induced IL-18 expression. ETAR 
      blockade BQ123 inhibited stretch-induced IL-18 expression. However, the 
      Endothelin B receptor (ETBR) receptor blockade BQ788 did not inhibit this 
      reaction. ET-1 induced IL-18 expression, with a peak induction after 4 hours of 
      incubation. These results might suggest that stretch stimulation of 
      cardiomyocytes induced ET-1 and, subsequently, ET-1 up-regulated the IL-18 
      expression. Furthermore, Fasudil, a Rho-Kinase inhibitor, and Simvastatin, a 
      HMG-CoA reductase inhibitor, led to a significant reduction in mechanical 
      stretch-induced IL-18 expression. These results indicated, for the first time, 
      that IL-18 expression is induced by mechanical stretch in cardiomyocytes via the 
      ETAR, AT1R, and the Rho/Rho-K pathways. The induction of IL-18 from 
      cardiomyocytes by mechanical stress might cause the deterioration of cardiac 
      functions in autocrine and paracrine fashion. The inhibition of IL-18 expression 
      induced by mechanical stress might be one of the mechanisms that account for the 
      beneficial cardiovascular effects of AT1R antagonist, ETAR blockade, Statin, and 
      Rho-Kinase inhibitor.
FAU - Naka, Toshio
AU  - Naka T
AD  - Department of Internal Medicine, Division of Coronary Heart Disease, Hyogo 
      College of Medicine, Nishinomiya, Hyogo, Japan.
FAU - Sakoda, Tsuyoshi
AU  - Sakoda T
FAU - Doi, Takashi
AU  - Doi T
FAU - Akagami, Takafumi
AU  - Akagami T
FAU - Tsujino, Takeshi
AU  - Tsujino T
FAU - Masuyama, Tohru
AU  - Masuyama T
FAU - Ohyanagi, Mitsumasa
AU  - Ohyanagi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Prep Biochem Biotechnol
JT  - Preparative biochemistry & biotechnology
JID - 9607037
RN  - 0 (Endothelin-1)
RN  - 0 (Interleukin-18)
RN  - 0 (Receptor, Angiotensin, Type 1)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cells, Cultured
MH  - Elasticity
MH  - Endothelin-1/*metabolism
MH  - Interleukin-18/*metabolism
MH  - Mechanotransduction, Cellular/*physiology
MH  - Myocytes, Cardiac/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1/*metabolism
MH  - Stress, Mechanical
EDAT- 2008/03/06 09:00
MHDA- 2008/04/17 09:00
CRDT- 2008/03/06 09:00
PHST- 2008/03/06 09:00 [pubmed]
PHST- 2008/04/17 09:00 [medline]
PHST- 2008/03/06 09:00 [entrez]
AID - 791221278 [pii]
AID - 10.1080/10826060701885704 [doi]
PST - ppublish
SO  - Prep Biochem Biotechnol. 2008;38(2):201-12. doi: 10.1080/10826060701885704.