Nonmuscle and Smooth Muscle Myosin Heavy Chain Expression in Rejected Cardiac Allografts

Suzuki, Jun–ichi; Isobe, Mitsuaki; Aikawa, Masamichi; Kawauchi, M; Shiojima, Ichiro; Kobayashi, Naoto; Tojo, Akihiro; Suzuki, Toru; Kimura, Kenjiro; Nishikawa, Toshio; Sakai, Tatsuo; Sekiguchi, Morie; Yazaki, Yoshio; Nagai, Ryozo

doi:10.1161/01.cir.94.5.1118

Cited by 75 publications

(43 citation statements)

References 20 publications

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“…1,2 Acute rejection is enhanced by several cytokines and adhesion molecules; the arteriopathy is characterized by intimal thickening comprised of proliferative smooth muscle cells (SMCs). 3,4 The use of DNA technology to regulate the transcription of disease-related genes in vivo has great therapeutic potential. Antisense cyclin-dependent kinase (cdk) 2 kinase oligodeoxynucleotide (ODN) and double-stranded DNA with high affinity for E2F (E2F decoy) 5,6 inhibit neointimal formation by suppressing multiple gene expression as demonstrated in rat carotid arterial injury models.…”

Section: Introductionmentioning

confidence: 99%

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

et al. 2000

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Acute rejection and graft arteriopathy in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by several cytokines and adhesion molecules. Nuclear factor-kappa B (NF B) is critical in the transcription of multiple genes involved in inflammation and cell proliferation. To test the hypothesis that NF B decoy can attenuate acute rejection and arteriopathy, we performed single intraluminal delivery of NF B decoy into murine cardiac allografts using a hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE)-liposome method. No decoy or scrambled decoy transfer was performed for control. Hearts were heterotopically transplanted from BALB/c to C3H/He mice (major mismatch group) and from DBA/2 to

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Section: Introductionmentioning

confidence: 99%

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

et al. 2000

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“…The ensuing endothelial dysfunction and injury result in the exposure of the underlying VSMC to mitogenic growth factors (13). This is followed by the phenotypic conversion of the VSMC from a normally contractile nonproliferating phenotype to the pathologic secretory proliferating phenotype observed in both restenosis and allograft arteriosclerosis (14,15).…”

Section: Introductionmentioning

confidence: 99%

Inducible nitric oxide synthase suppresses the development of allograft arteriosclerosis.

Shears

Kawaharada²,

Tzeng³

et al. 1997

J. Clin. Invest.

234

128

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In cardiac transplantation, chronic rejection takes the form of an occlusive vasculopathy. The mechanism underlying this disorder remains unclear. The purpose of this study was to investigate the role nitric oxide (NO) may play in the development of allograft arteriosclerosis. Rat aortic allografts from ACI donors to Wistar Furth recipients with a strong genetic disparity in both major and minor histocompatibility antigens were used for transplantation. Allografts collected at 28 d were found to have significant increases in both inducible NO synthase (

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“…In humans and rabbit, SM-1 is expressed during early fetal development with SM-2 appearing only after birth in what is thought to be the fully differentiated or mature SMC (12)(13)(14). Moreover, several studies have shown that SM-MHC expression is significantly decreased in vascular lesions (12,15), and the loss of this marker protein has been used to evaluate the differentiated state of the SMC as related to vascular disease progression (16,17). Thus, SM-MHC represents an excellent gene for delineating the transcriptional regulatory mechanisms that define the differentiated state of the SMC.…”

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confidence: 99%

Interaction of CArG Elements and a GC-rich Repressor Element in Transcriptional Regulation of the Smooth Muscle Myosin Heavy Chain Gene in Vascular Smooth Muscle Cells

Madsen¹,

Regan

Owens

1997

Journal of Biological Chemistry

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We have previously shown that maximal expression of the rat smooth muscle myosin heavy chain (SM-MHC) gene in cultured rat aortic smooth muscle cells (SMCs) required the presence of a highly conserved domain (nucleotides ؊1321 and ؊1095) that contained two positive-acting serum response factor (SRF) binding elements (CArG boxes 1 and 2) and a negative-acting GCrich element that was recognized by Sp1 (Madsen, C. S., Hershey, J. C., Hautmann, M. B., White, S. L., and Owens, G. K. (1997) J. Biol. Chem. 272, 6332-6340). In this study, to better understand the functional role of these three cis elements, we created a series of SM-MHC reportergene constructs in which each element was mutated either alone or in combination with each other and tested them for activity in transient transfection assays using primary cultured rat aortic SMCs. Results demonstrated that the most proximal SRF binding element (CArG-box1) was active in the absence of CArG-box2, but only upon removal of the GC-rich repressor. In contrast, regardless of sequence context, CArG-box2 was active only when CArG-box1 was present. We further demonstrated using electrophoretic mobility shift assays that Sp1 binding to the GC-rich repressor element did not prevent SRF binding to the adjacent CArG-box2. Thus, unlike other proteins reported to inhibit SRF activity, the repressor activity associated with the GC-rich element does not appear to function through direct inhibition of SRF binding. As a first step toward understanding the importance of these elements in vivo, we performed in vivo footprinting on the intact rat aorta. We demonstrated that both CArG boxes and the GC-rich element were bound by protein within the animal. Additionally, using the rat carotid injury model we showed that Sp1 protein was significantly increased in SMCs located within the myointimal lesion, suggesting that increased expression of this putative repressor factor may contribute to the decreased SM MHC expression within SMCs found in myointimal lesions.

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Nonmuscle and Smooth Muscle Myosin Heavy Chain Expression in Rejected Cardiac Allografts

Abstract: Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.

Cited by 75 publications

References 20 publications

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

Inducible nitric oxide synthase suppresses the development of allograft arteriosclerosis.

Interaction of CArG Elements and a GC-rich Repressor Element in Transcriptional Regulation of the Smooth Muscle Myosin Heavy Chain Gene in Vascular Smooth Muscle Cells

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