Publications (91) View all
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Article: Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure.
Toshio Nishikimi, Hiroyuki Okamoto, Masahiro Nakamura, Naoko Ogawa, Kazukiyo Horii, Kiyoshi Nagata, Yasuaki Nakagawa, Hideyuki Kinoshita, Chinatsu Yamada, Kazuhiro Nakao, Takeya Minami, Yoshihiro Kuwabara, Koichiro Kuwahara, Izuru Masuda, Kenji Kangawa, Naoto Minamino, Kazuwa Nakao[show abstract] [hide abstract]
ABSTRACT: Recent studies have shown that in addition to brain (or B-type) natriuretic peptide (BNP) and the N-terminal proBNP fragment, levels of intact proBNP are also increased in heart failure. Moreover, present BNP immunoassays also measure proBNP, as the anti-BNP antibody cross-reacts with proBNP. It is important to know the exact levels of proBNP in heart failure, because elevation of the low-activity proBNP may be associated with the development of heart failure. We therefore established a two-step immunochemiluminescent assay for total BNP (BNP+proBNP) and proBNP using monoclonal antibodies and glycosylated proBNP as a standard. The assay enables measurement of plasma total BNP and proBNP within only 7 h, without prior extraction of the plasma. The detection limit was 0.4 pmol/L for a 50-µl plasma sample. Within-run CVs ranged from 5.2%-8.0% in proBNP assay and from 7.0%-8.4% in total BNP assay, and between-run CVs ranged from 5.3-7.4% in proBNP assay and from 2.9%-9.5% in total BNP assay, respectively. The dilution curves for plasma samples showed good linearity (correlation coefficients = 0.998-1.00), and analytical recovery was 90-101%. The mean total BNP and proBNP in plasma from 116 healthy subjects were 1.4±1.2 pM and 1.0±0.7 pM, respectively, and were 80±129 pM and 42±70 pM in 32 heart failure patients. Plasma proBNP levels significantly correlate with age in normal subjects. Our immunochemiluminescent assay is sufficiently rapid and precise for routine determination of total BNP and proBNP in human plasma.PLoS ONE 01/2013; 8(1):e53233. · 4.09 Impact Factor -
Article: Complexity of molecular forms of B-type natriuretic peptide in heart failure.
Heart (British Cardiac Society) 10/2012; · 4.22 Impact Factor -
Article: Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice.
Takeya Minami, Koichiro Kuwahara, Yasuaki Nakagawa, Minoru Takaoka, Hideyuki Kinoshita, Kazuhiro Nakao, Yoshihiro Kuwabara, Yuko Yamada, Chinatsu Yamada, Junko Shibata, [......], Toshio Nishikimi, Kenji Ueshima, Masataka Sata, Hiroyasu Nakano, Takahiro Seno, Yutaka Kawahito, Kenji Sobue, Akinori Kimura, Ryozo Nagai, Kazuwa Nakao[show abstract] [hide abstract]
ABSTRACT: Myocardin-related transcription factor (MRTF)-A is a Rho signalling-responsive co-activator of serum response factor (SRF). Here, we show that induction of MRTF-A expression is key to pathological vascular remodelling. MRTF-A expression was significantly higher in the wire-injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE(-/-) mice than in healthy control tissues, whereas myocardin expression was significantly lower. Both neointima formation in wire-injured femoral arteries in MRTF-A knockout (Mkl1(-/-)) mice and atherosclerotic lesions in Mkl1(-/-); ApoE(-/-) mice were significantly attenuated. Expression of vinculin, matrix metallopeptidase 9 (MMP-9) and integrin β1, three SRF targets and key regulators of cell migration, in injured arteries was significantly weaker in Mkl1(-/-) mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs was the downregulation of microRNA-1. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. MRTF-A could thus be a novel therapeutic target for the treatment of vascular diseases.The EMBO Journal 10/2012; · 9.20 Impact Factor -
Article: Effect of a Hypocaloric Diet on Adrenomedullin and Natriuretic Peptides in Obese Patients with Essential Hypertension
Junichi Minami, Toshio Nishikimi, Toshihiko Ishimitsu, Yuriko Makino, Yuhei Kawano, Shuichi Takishita, Kenji Kangawa, Hiroaki MatsuokaJournal of Cardiovascular Pharmacology 08/2012; 36:S83-S86. · 2.29 Impact Factor -
Article: Transcriptional regulation of the fetal cardiac gene program.
Koichiro Kuwahara, Toshio Nishikimi, Kazuwa Nakao[show abstract] [hide abstract]
ABSTRACT: Reactivation of the fetal cardiac gene program in adults is a reliable marker of cardiac hypertrophy and heart failure. Normally, genes within this group are expressed in the fetal ventricles during development, but are silent after birth. However, their expression is re-induced in the ventricular myocardium in response to various cardiovascular diseases, and potentially plays an important role in the pathological process of cardiac remodeling. Thus, analysis of the molecular mechanisms that govern the expression of fetal cardiac genes could lead to the discovery of transcriptional regulators and signaling pathways involved in both cardiac differentiation and cardiac disease. In this review we will summarize what is currently known about the transcriptional regulation of the fetal cardiac gene program.Journal of Pharmacological Sciences 06/2012; 119(3):198-203. · 2.08 Impact Factor