Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.
Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.
复制标题
寄生前2型糖尿病通过心脏重塑和纤维化诱导鼠类胚胎中的心脏肥大。
DOI：
10.1016/j.ajog.2017.04.008
复制
发表时间：
2017-08
影响因子：
9.8
通讯作者：
Yang P
中科院分区：
文献类型：
--
作者：
Lin X;Yang P;Reece EA;Yang P
心脏肥大在2型糖尿病（T2 DM）患者中非常普遍。实验证据表明，T2 DM孕妇及其子女患心血管疾病的风险增加。我们之前的小鼠模型研究表明，母体T2 DM诱导其后代的结构性心脏缺陷。本研究旨在确定母体T2 DM是否在糖尿病胚胎病小鼠模型中诱导胚胎心脏肥大。通过用高脂饮食（HFD）喂养4周龄雌性C57 BL/6 J小鼠15周来建立T2 DM胚胎病模型。通过测量心脏大小、左右心室壁和室间隔厚度以及β-肌球蛋白重链（β-MHC）、心房利钠肽（ANP）、胰岛素样生长因子1（IGF 1）、结蛋白（DES）和肾上腺髓质素（ADM）的表达来表征胚胎17.5天的心脏肥大。通过胶原合成和纤维连接蛋白合成来确定心脏重构。通过Masson染色并测定结缔组织生长因子（CTGF）、骨桥蛋白（OPN）和半乳糖凝集素3（GAL 3）基因的表达来评估纤维化。在发育中的心脏中也测量了细胞凋亡。妊娠糖尿病组胚胎心脏的左室壁和室间隔厚度明显大于非糖尿病组。母体糖尿病显著增加了β-MHC、ANP、IGF 1和DES的表达，但降低了ADM的表达。此外，在糖尿病母鼠的胚胎心脏中，胶原合成显著增加，而纤维连接蛋白合成受到抑制，表明心脏重构是心脏肥大的一个促进因素。心脏纤维化标志物GAL 3由母体糖尿病诱导。此外，T2 DM组母亲的JNK 1/2应激信号通路激活，TUNEL阳性细胞数增加（T2 DM组10.4 ± 2.2%vs.ND组3.8 ± 0.7%，P < 0.05）。母体T2 DM诱导胚胎心脏肥大。不良的心脏重塑，包括胶原合成增加、纤维连接蛋白合成抑制、促纤维化和细胞凋亡，被认为是心脏肥大的病因。
Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Experimental evidence has implied that pregnant women with T2DM and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study has revealed that maternal T2DM induces structural heart defects in their offspring. The present study aims to determine whether maternal T2DM induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The T2DM embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet (HFD) for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), insulin-like growth factor 1 (IGF1), desmin (DES), and adrenomedullin (ADM). Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor (CTGF), osteopontin (OPN), and Galectin 3 (GAL3) genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic (ND) group. Maternal diabetes significantly increased β-MHC, ANP, IGF1 and DES expression, but decreased expression of ADM. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, GAL3, was induced by maternal diabetes. Furthermore, maternal T2DM activated the pro-apoptotic c-Jun-N-terminal kinase (JNK1/2) stress signaling and triggered cell apoptosis by increasing the number of TUNEL positive cells (10.4 ± 2.2% of the T2DM group vs. 3.8 ± 0.7% of the ND group, P < 0.05). Maternal T2DM induces cardiac hypertrophy in embryonic hearts. Adverse cardiac remodeling, including elevated collagen synthesis, suppressed fibronectin synthesis, profibrosis and apoptosis, is implicated as the etiology of cardiac hypertrophy.
登录
查看更多内容
DOI：
10.1016/0002-9378(94)90102-3
发表时间：
1994-09-01
影响因子：
9.8
作者：
CIPOLLA, M;OSOL, G
通讯作者：
OSOL, G
影响因子：
9.8
作者：
Cain, Mary Ashley;Salemi, Jason L.;Louis, Judette M.
通讯作者：
Louis, Judette M.
影响因子：
4.8
作者：
Bisping, Egbert;Ikeda, Sadakatsu;Pieske, Burkert
通讯作者：
Pieske, Burkert
影响因子：
20.1
作者：
Evans SM;Yelon D;Conlon FL;Kirby ML
通讯作者：
Kirby ML
胎儿人心脏的左心室和右心室之间的内在肌构造差异：超声波反向散射可行性研究。
DOI：
10.1016/j.echo.2008.11.028
发表时间：
2009-02
影响因子：
6.5
作者：
Holland, Mark R.;Gibson, Allyson A.;Kirschner, Carol A.;Hicks, Deborah;Ludomirsky, Achiau;Singh, Gautam K.
通讯作者：
Singh, Gautam K.