Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts.
Am J Physiol Endocrinol Metab. 2020 Aug 1;319(2):E363-E375. doi: 10.1152/ajpendo.00362.2019. Epub 2020 Jun 30.
Bone morphogenetic protein (BMP) receptor signaling is critical for the regulation of the endocrine system and cardiovascular structure and function. The objective of this study was to investigate whether Bmp3b, a glycoprotein synthetized and secreted by adipose tissue, is necessary to regulate glucose and lipid metabolism, adipogenesis, and cardiovascular remodeling. Over the course of 4 mo, -knockout () mice gained more weight than wild-type (WT) mice. The plasma levels of cholesterol and triglycerides were higher in mice than in WT mice. mice developed insulin resistance and glucose intolerance. The basal heart rate was higher in mice than in WT mice, and echocardiography revealed eccentric remodeling in mice. The expression of adipogenesis-related genes in white adipose tissue was higher in mice than in WT control mice. In vitro studies showed that Bmp3b modulates the activity of the promoter, an effect mediated by Smad2/3. The results of this study suggest that Bmp3b is necessary for the maintenance of homeostasis in terms of age-related weight gain, glucose metabolism, and left ventricular (LV) remodeling and function. Interventions that increase the level or function of BMP3b may decrease cardiovascular risk and pathological cardiac remodeling.
骨形态发生蛋白（BMP）受体信号对于内分泌系统和心血管结构与功能的调节至关重要。本研究旨在探讨脂肪组织合成和分泌的糖蛋白 Bmp3b 是否对于调节葡萄糖和脂质代谢、脂肪生成以及心血管重塑具有必要性。在 4 个月的时间里，-基因敲除（）小鼠比野生型（WT）小鼠体重增加更多。血浆胆固醇和甘油三酯水平在 小鼠中高于 WT 小鼠。 小鼠出现胰岛素抵抗和葡萄糖不耐受。基础心率在 小鼠中高于 WT 小鼠，超声心动图显示 小鼠存在偏心性重塑。白色脂肪组织中与脂肪生成相关的基因表达在 小鼠中高于 WT 对照组。体外研究表明，Bmp3b 通过 Smad2/3 调节启动子的活性，这一效应。本研究结果表明，Bmp3b 对于维持与年龄相关的体重增加、葡萄糖代谢以及左心室（LV）重塑和功能的体内平衡是必要的。增加 BMP3b 水平或功能的干预措施可能会降低心血管风险和病理性心脏重塑。
