RGD Reference Report - A nuclear factor-kappaB inhibitor pyrrolidine dithiocarbamate ameliorates pulmonary hypertension in rats. - Rat Genome Database

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A nuclear factor-kappaB inhibitor pyrrolidine dithiocarbamate ameliorates pulmonary hypertension in rats.

Authors: Sawada, H  Mitani, Y  Maruyama, J  Jiang, BH  Ikeyama, Y  Dida, FA  Yamamoto, H  Imanaka-Yoshida, K  Shimpo, H  Mizoguchi, A  Maruyama, K  Komada, Y 
Citation: Sawada H, etal., Chest. 2007 Oct;132(4):1265-74.
RGD ID: 2298843
Pubmed: PMID:17934115   (View Abstract at PubMed)
DOI: DOI:10.1378/chest.06-2243   (Journal Full-text)

BACKGROUND: Pulmonary hypertension (PH) is a fatal disorder that is associated with structural changes and inflammatory responses in the pulmonary vasculature. Nuclear factor (NF)-kappaB is a key transcription factor that is involved in the tissue remodeling mediated by inflammatory and fibroproliferative responses. However, the contribution of NF-kappaB-mediated inflammatory pathways to the development of PH is unknown. METHODS: We therefore investigated whether NF-kappaB activation and the expression of a downstream product vascular cell adhesion molecule (VCAM)-1 is associated with pulmonary vascular diseases in rats that have been injected with the toxin monocrotaline (MCT), and whether a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), ameliorates such diseases in rats. RESULTS: VCAM-1 expression and the nuclear localization of the p65 subunit of NF-kappaB, as analyzed immunohistochemically, was significantly up-regulated in the endothelium of diseased vessels on the days 8 to 22 (p < 0.05). Next, 39 rats were divided into three groups (rats injected with MCT and treated with saline solution or PDTC, and controls similarly treated with saline solution). Compared to controls, MCT treatment increased the mean (+/- SE) pulmonary artery pressure (31.2 +/- 1.4 mm Hg [p < 0.05] vs 22.8 +/- 0.9 mm Hg, respectively), which was reduced by PDTC treatment (24.3 +/- 1.2 mm Hg; p < 0.05). Indexes of right ventricular hypertrophy and pulmonary vascular diseases induced by MCT were similarly inhibited (p < 0.05), which was associated with the suppression of VCAM-1 expression and macrophage infiltration. CONCLUSIONS: We concluded that the NF-kappaB nuclear localization and VCAM-1 expression is temporally and spatially associated with the development of MCT-induced PH in rats, which was ameliorated by administering a NF-kappaB inhibitor, PDTC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary hypertension  ISORela (Rattus norvegicus)2298843; 2298843protein:altered localization:nucleus more ...RGD 
pulmonary hypertension  IEP 2298843protein:altered localization:nucleus more ...RGD 
pulmonary hypertension  ISOVcam1 (Rattus norvegicus)2298843; 2298843protein:increased expression:blood vessel endotheliumRGD 
pulmonary hypertension  IEP 2298843protein:increased expression:blood vessel endotheliumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Rela  (RELA proto-oncogene, NF-kB subunit)
Vcam1  (vascular cell adhesion molecule 1)

Genes (Mus musculus)
Rela  (v-rel reticuloendotheliosis viral oncogene homolog A (avian))
Vcam1  (vascular cell adhesion molecule 1)

Genes (Homo sapiens)
RELA  (RELA proto-oncogene, NF-kB subunit)
VCAM1  (vascular cell adhesion molecule 1)


Additional Information