期刊
FASEB JOURNAL
卷 22, 期 8, 页码 3010-3023出版社
WILEY
DOI: 10.1096/fj.07-100966
关键词
cardiac myocytes; endothelial cells; integrinlinked kinase; AMP-activated protein kinase; Tie2
资金
- NCI NIH HHS [P01-CA45548, R21 CA107976-01, P01 CA045548-20, R21 CA107976, P01 CA045548, R21 CA107976-02, R21-CA107976-01] Funding Source: Medline
- NHLBI NIH HHS [K02 HL071840, K02 HL071840-05, K02 HL071840-04, K02-HL071840-01] Funding Source: Medline
- NIDDK NIH HHS [K01-DK063970-01, K01 DK063970, K01 DK063970-02, K01 DK063970-03] Funding Source: Medline
Angiopoietins were thought to be endothelial cell-specific via the tie2 receptor. We showed that angiopoietin-1 (ang1) also interacts with integrins on cardiac myocytes (CMs) to increase survival. Because ang1 monomers bind and activate integrins (not tie2), we determined their function in vivo. We examined monomer and multimer expressions during physiological and pathological cardiac remodeling and overexpressed ang1 monomers in phenylephrine-induced cardiac hypertrophy. Cardiac ang1 levels (mRNA, protein) increased during postnatal development and decreased with phenylephrine-induced cardiac hypertrophy, whereas tie2 phosphorylations were unchanged. We found that most or all of the changes during cardiac remodeling were in monomers, offering an explanation for unchanged tie2 activity. Heart tissue contains abundant ang1 monomers and few multimers (Western blotting). We generated plasmids that produce ang1 monomers (ang1-256), injected them into mice, and confirmed cardiac expression (immunohistochemistry, RT-PCR). Ang1 monomers localize to CMs, smooth muscle cells, and endothelial cells. In phenylephrine-induced cardiac hypertrophy, ang1-256 reduced left ventricle (LV)/tibia ratios, fetal gene expressions (atrial and brain natriuretic peptides, skeletal actin, beta-myosin heavy chain), and fibrosis (collagen III), and increased LV prosurvival signaling (akt, MAPK(p42/44)), and AMPK(T172). However, tie2 phosphorylations were unchanged. Ang1-256 increased integrin-linked kinase, a key regulator of integrin signaling and cardiac health. Collectively, these results.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据