Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart

被引：62

作者：

Zhou, Bin ^{[1
,2
,3
,8
]}

Ma, Qing ^{[1
,2
]}

Kong, Sek Won ^{[1
,2
]}

Hu, Yongwu ^{[1
,2
,4
]}

Campbell, Patrick H. ^{[5
]}

McGowan, Francis X. ^{[5
]}

Ackerman, Kate G. ^{[6
,7
]}

Wu, Bingruo ^{[8
]}

Zhou, Bin ^{[1
,2
,3
,8
]}

Tevosian, Sergei G. ^{[9
,10
]}

Pu, William T. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[4] Wenzhou Med Coll, Sch Life Sci, Dept Biol, Wenzhou, Zhejiang, Peoples R China

[5] Childrens Hosp Boston, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA

[6] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA

[7] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA

[8] Albert Einstein Coll Med, Dept Genet, New York, NY USA

[9] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Genet, Hanover, NH 03756 USA

[10] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Norris Cotton Canc Ctr, Hanover, NH 03756 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2009年 / 119卷 / 06期

关键词：

SMOOTH-MUSCLE-CELLS; FIBROBLAST GROWTH FACTOR-2; EPICARDIUM-DERIVED CELLS; VENTRAL MORPHOGENESIS; TRANSCRIPTION FACTORS; TUBE FORMATION; GATA4; EXPRESSION; FAILURE; ANGIOGENESIS;

D O I：

10.1172/JCI38723

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Aberrant transcriptional regulation contributes to the pathogenesis of both congenital and adult forms of heart disease. While the transcriptional regulator friend of Gata 2 (FOG2) is known to be essential for heart morphogenesis and coronary development, its tissue-specific function has not been previously investigated. Additionally, little is known about the role of FOG2 in the adult heart. Here we used spatiotemporally regulated inactivation of Fog2 to delineate its function in both the embryonic and adult mouse heart. Early cardiomyocyte-restricted loss of Fog2 recapitulated the cardiac and coronary defects of the Fog2 germline murine knockouts. Later cardiomyocyte-restricted loss of Fog2 (Fog2(MC)) did not result in defects in cardiac structure or coronary vessel formation. However, Fog2(MC) adult mice had severely depressed ventricular function and died at 8-14 weeks. Fog2(MC) adult hearts displayed a paucity of coronary vessels, associated with myocardial hypoxia, increased cardiomyocyte apoptosis, and cardiac fibrosis. Induced inactivation of Fog2 in the adult mouse heart resulted in similar phenotypes, as did ablation of the FOG2 interaction with the transcription factor GATA4. Loss of the FOG2 or FOG2-GATA4 interaction altered the expression of a panel of angiogenesis-related genes. Collectively, our data indicate that FOG2 regulates adult heart function and coronary angiogenesis.

引用

页码：1462 / 1476

页数：15

共 47 条

[1] Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure [J].

Bisping, Egbert ;

Ikeda, Sadakatsu ;

Kong, Sek Won ;

Tarnavski, Oleg ;

Bodyak, Natalya ;

McMullen, Julie R. ;

Rajagopal, Satish ;

Son, Jennifer K. ;

Ma, Qing ;

Springer, Zhangli ;

Kang, Peter M. ;

Izumo, Seigo ;

Pu, William T. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (39) :14471-14476

[2] A myocardial lineage derives from Tbx18 epicardial cells [J].

Cai, Chen-Leng ;

Martin, Jody C. ;

Sun, Yunfu ;

Cui, Li ;

Wang, Lianchun ;

Ouyang, Kunfu ;

Yang, Lei ;

Bu, Lei ;

Liang, Xingqun ;

Zhang, Xiaoxue ;

Stallcup, William B. ;

Denton, Christopher P. ;

McCulloch, Andrew ;

Chen, Ju ;

Evans, Sylvia M. .

NATURE, 2008, 454 (7200) :104-U4

[3] Coregulation of GATA factors by the Friend of GATA (FOG) family of multitype zinc finger proteins [J].

Cantor, AB ;

Orkin, SH .

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2005, 16 (01) :117-128

[4] Angiogenesis in life, disease and medicine [J].

Carmeliet, P .

NATURE, 2005, 438 (7070) :932-936

[5] Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors [J].

Crispino, JD ;

Lodish, MB ;

Thurberg, BL ;

Litovsky, SH ;

Collins, T ;

Molkentin, JD ;

Orkin, SH .

GENES & DEVELOPMENT, 2001, 15 (07) :839-844

[6] Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase [J].

Danielian, PS ;

Muccino, D ;

Rowitch, DH ;

Michael, SK ;

McMahon, AP .

CURRENT BIOLOGY, 1998, 8 (24) :1323-1326

[7] Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice [J].

Eklund, L ;

Piuhola, J ;

Komulainen, J ;

Sormunen, R ;

Ongvarrasopone, C ;

Fässler, R ;

Muona, A ;

Ilves, M ;

Ruskoaho, H ;

Takala, TES ;

Pihlajaniemi, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (03) :1194-1199

[8] Recent advances in cardiac development with therapeutic implications for adult cardiovascular disease [J].

Epstein, JA ;

Parmacek, MS .

CIRCULATION, 2005, 112 (04) :592-597

[9] Antiangiogenesis in cancer therapy - endostatin and its mechanisms of action [J].

Folkman, J .

EXPERIMENTAL CELL RESEARCH, 2006, 312 (05) :594-607

[10] Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3 [J].

Gaussin, V ;

Van de Putte, T ;

Mishina, Y ;

Hanks, MC ;

Zwijsen, A ;

Huylebroeck, D ;

Behringer, RR ;

Schneider, MD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (05) :2878-2883

← 1 2 3 4 5 →