Regulation of vascular tone and remodeling of the ductus arteriosus
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概要
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The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The DA is a normal and essential fetal structure. However, it becomes abnormal if it remains patent after birth. Closure of the DA occurs in two phases: functional closure of the lumen within the first hours after birth by smooth muscle constriction, and anatomic occlusion of the lumen over the next several days due to extensive neointimal thickening in human DA. There are several events that promote the DA constriction immediately after birth: (a) an increase in arterial oxygen tension, (b) a dramatic decline in circulating prostaglandinE2 (PGE2), (c) a decrease in blood pressure within the DA lumen, and (d) a decrease in the number of PGE2 receptors in the DA wall. Anatomical closure of the DA is associated with the formation of intimal thickening, which are characterized by (a) an area of subendothelial deposition of extracellular matrix, (b) the disassembly of the internal elastic lamina and loss of elastic fiber in the medial layer, and (c) migration into the subendothelial space of undifferentiated medial smooth muscle cells. In addition to the well-known vasodilatory role of PGE2, our findings uncovered the role of PGE2 in anatomical closure of the DA. Chronic PGE2-EP4-cyclic AMP (cAMP)-protein kinase A (PKA) signaling during gestation induces vascular remodeling of the DA to promote hyaluronan-mediated intimal thickening and structural closure of the vascular lumen. A novel target of cAMP, Epac, has an acute promoting effect on smooth muscle cell migration without hyaluronan production and thus intimal thickening in the DA. Both EP4-cAMP downstream targets, Epac and PKA, regulate vascular remodeling in the DA.
- 2010-04-01
著者
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Minamisawa Susumu
Department Of Life Science And Medical Bio-science Waseda University Graduate School Of Advanced Sci
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Minamisawa Susumu
Department Of Physiology Yokohama City University School Of Medicine
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Minamisawa Susumu
Department Of Life Science And Medical Bio-science Waseda University Advanced Science And Engineerin
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Ishikawa Yoshihiro
Cardiovascular Research Institute Yokohama City University Graduate School Of Medicine
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Ishikawa Yosiyuki
横浜市立大学 循環器内科
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Ishikawa Yoshihiro
横浜市立大学附属市民総合医療センター 心臓血管センター
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Minamisawa Susumu
Cardiovascular Research Institute Yokohama City University School Of Medicine
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Yokoyama Utako
Cardiovascular Research Institute Yokohama City University Graduate School Of Medicine
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Ishikawa Yoshihiro
Cardiovascular Research Institute Yokohama City University
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Ishikawa Yoshihiro
Cardiovascular Research Institute Department Of Cell Biology And Molecular Medicine University Of Me
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Ishikawa Yoshihiro
Department Of Physiology Yokohama City University
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Yokoyama Utako
Cardiovascular Research Institute Yokohama City University
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