Potential Therapeutic Targets for Cardiac Fibrosis TGFβ, Angiotensin, Endothelin, CCN2, and PDGF, Partners in Fibroblast Activation

被引:588
作者
Leask, Andrew [1 ]
机构
[1] Schulich Sch Med & Dent, Dept Dent, London, ON, Canada
关键词
PDGF; TGF beta; endothelin; fibrosis; scarring; GROWTH-FACTOR-BETA; SMOOTH-MUSCLE-CELLS; MICE LACKING SMAD3; MYOFIBROBLAST DIFFERENTIATION; IN-VIVO; MYOCARDIAL FIBROSIS; MATRIX CONTRACTION; FIBROTIC PHENOTYPE; DERMAL FIBROBLASTS; GENE-REGULATION;
D O I
10.1161/CIRCRESAHA.110.217737
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, "activated" fibroblasts migrate into the wound area, where they synthesize and remodel newly created extracellular matrix. The specialized type of fibroblast responsible for this action is the alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblast. Abnormal persistence of the myofibroblast is a hallmark of fibrotic diseases. Proteins such as transforming growth factor (TGF)beta, endothelin-1, angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to myofibroblast differentiation and persistence. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF beta, endothelin-1, Ang II, CCN2, and PDGF and to fibroblast activation in tissue repair and fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of cardiac fibrosis. (Circ Res. 2010; 106: 1675-1680.)
引用
收藏
页码:1675 / 1680
页数:6
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