TY - JOUR
T1 - Inflammatory cytokines cause coronary arteriosclerosis-like changes and alterations in the smooth-muscle phenotypes in pigs
AU - Fukumoto, Yoshihiro
AU - Shimokawa, Hiroaki
AU - Ito, Akira
AU - Kadokami, Toshiaki
AU - Yonemitsu, Yoshikazu
AU - Aikawa, Masanori
AU - Owada, M. Koji
AU - Egashira, Kensuke
AU - Sueishi, Katsuo
AU - Nagai, Ryozo
AU - Yazaki, Yoshio
AU - Takeshita, Akira
PY - 1997/2
Y1 - 1997/2
N2 - We recently developed a porcine model in which chronic, local treatment with interleukin-1β (IL-1β) causes coronary arteriosclerosis-like changes and hyperconstrictive responses. This study was designed to examine whether or not other major inflammatory cytokines [tumor necrosis factor-α (TNF- α) and interleukin-1α (IL-1α)] might also cause similar coronary responses and whether those responses are associated with alterations in the smooth-muscle phenotypes. A segment of the porcine coronary artery was aseptically wrapped with cotton mesh, absorbing IL-1β, TNF-α, and IL-1α. Two weeks after the operation, coronary arteriography showed the development of mild stenotic lesions at the cytokine-treated sites, where hyperconstrictive responses were repeatedly induced by intracoronary serotonin or histamine. Histologically mild intimal thickening was noted at those cytokine-treated sites. Immunostaining and immunoblotting demonstrated that all three myosin heavy chain isoforms, SM1, SM2 (smooth-muscle type), and SMemb (nonmuscle type), were noted in the normal coronary segments, whereas in the segments treated with inflammatory cytokines, SM1 and SM2 were markedly reduced, and only SMemb was noted. These results indicate that inflammatory cytokines all have a similar ability to induce coronary arteriosclerosis-like changes and hyperconstrictive responses, which are associated with alterations in smooth-muscle phenotypes toward dedifferentiation.
AB - We recently developed a porcine model in which chronic, local treatment with interleukin-1β (IL-1β) causes coronary arteriosclerosis-like changes and hyperconstrictive responses. This study was designed to examine whether or not other major inflammatory cytokines [tumor necrosis factor-α (TNF- α) and interleukin-1α (IL-1α)] might also cause similar coronary responses and whether those responses are associated with alterations in the smooth-muscle phenotypes. A segment of the porcine coronary artery was aseptically wrapped with cotton mesh, absorbing IL-1β, TNF-α, and IL-1α. Two weeks after the operation, coronary arteriography showed the development of mild stenotic lesions at the cytokine-treated sites, where hyperconstrictive responses were repeatedly induced by intracoronary serotonin or histamine. Histologically mild intimal thickening was noted at those cytokine-treated sites. Immunostaining and immunoblotting demonstrated that all three myosin heavy chain isoforms, SM1, SM2 (smooth-muscle type), and SMemb (nonmuscle type), were noted in the normal coronary segments, whereas in the segments treated with inflammatory cytokines, SM1 and SM2 were markedly reduced, and only SMemb was noted. These results indicate that inflammatory cytokines all have a similar ability to induce coronary arteriosclerosis-like changes and hyperconstrictive responses, which are associated with alterations in smooth-muscle phenotypes toward dedifferentiation.
KW - Atherosclerosis
KW - Cytokines
KW - Interleukin-1α
KW - Interleukin-1β
KW - Tumor necrosis factor- α
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U2 - 10.1097/00005344-199702000-00011
DO - 10.1097/00005344-199702000-00011
M3 - Article
C2 - 9057072
AN - SCOPUS:0031030303
VL - 29
SP - 222
EP - 231
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 2
ER -