Tsukamoto Osamu, Fujita Masashi, Kato Mahoto, Yamazaki Satoru, Asano Yoshihiro, Ogai Akiko, Okazaki Hidetoshi, Asai Mitsutoshi, Nagamachi Yoko, Maeda Norikazu, Shintani Yasunori, Minamino Tetsuo, Asakura Masanori, Kishimoto Ichiro, Funahashi Tohru, Tomoike Hitonobu, Kitakaze Masafumi
Cardiovascular Division of Medicine, National Cardiovascular Center, Suita, Osaka, Japan.
J Am Coll Cardiol. 2009 Jun 2;53(22):2070-7. doi: 10.1016/j.jacc.2009.02.038.
We investigated the functional relationship between natriuretic peptides and adiponectin by performing both experimental and clinical studies.
Natriuretic peptides are promising candidates for the treatment of congestive heart failure (CHF) because of their wide range of beneficial effects on the cardiovascular system. Adiponectin is a cytokine derived from adipose tissue with various cardiovascular-protective effects that has been reported to show a positive association with plasma brain natriuretic peptide (BNP) levels in patients with heart failure.
The expression of adiponectin messenger ribonucleic acid (mRNA) and its secretion were examined after atrial natriuretic peptide (ANP) or BNP was added to primary cultures of human adipocytes in the presence or absence of HS142-1 (a functional type A guanylyl cyclase receptor antagonist). Changes of the plasma adiponectin level were determined in 30 patients with CHF who were randomized to receive intravenous ANP (0.025 microg/kg/min human ANP for 3 days, n = 15) or saline (n = 15).
Both ANP and BNP dose-dependently enhanced the expression of adiponectin mRNA and its secretion, whereas such enhancement was inhibited by pre-treatment with HS142-1. The plasma adiponectin level was increased at 4 days after administration of human ANP compared with the baseline value (from 6.56 +/- 0.40 microg/ml to 7.34 +/- 0.47 microg/ml, p < 0.05), whereas there was no change of adiponectin in the saline group (from 6.53 +/- 0.57 microg/ml to 6.55 +/- 0.56 microg/ml).
Natriuretic peptides enhance adiponectin production by human adipocytes in vitro and even in patients with CHF, which might have a beneficial effect on cardiomyocytes in patients receiving recombinant natriuretic peptide therapy for heart failure.
我们通过开展实验研究和临床研究，探究了利钠肽与脂联素之间的功能关系。
利钠肽因其对心血管系统具有广泛的有益作用，有望成为治疗充血性心力衰竭（CHF）的药物。脂联素是一种源自脂肪组织的细胞因子，具有多种心血管保护作用，据报道，其与心力衰竭患者的血浆脑钠肽（BNP）水平呈正相关。
在有或无HS142 - 1（一种功能性A型鸟苷酸环化酶受体拮抗剂）存在的情况下，将心房利钠肽（ANP）或BNP添加到原代培养的人脂肪细胞中，检测脂联素信使核糖核酸（mRNA）的表达及其分泌情况。在30例CHF患者中测定血浆脂联素水平的变化，这些患者被随机分为两组，分别接受静脉注射ANP（0.025μg/kg/min人ANP，持续3天，n = 15）或生理盐水（n = 15）。
ANP和BNP均剂量依赖性地增强脂联素mRNA的表达及其分泌，而这种增强作用被HS142 - 1预处理所抑制。与基线值相比，注射人ANP 4天后血浆脂联素水平升高（从6.56±0.40μg/ml升至7.34±0.47μg/ml，p < 0.05），而生理盐水组脂联素水平无变化（从6.53±0.57μg/ml升至6.55±0.56μg/ml）。
利钠肽在体外甚至在CHF患者体内均可增强人脂肪细胞的脂联素生成，这可能对接受重组利钠肽治疗心力衰竭的患者的心肌细胞产生有益作用。
