所属 医学部 医学科（東京女子医科大学病院） 職種 特任教授
|発表タイトル||Developmental Difference in Maturation of Sarcoplasmic Reticulum in the Large Blood Vessels Influences Their Contractility|
|会議名||American Heart Association Scientific Sessions 2011|
|発表者・共同発表者||◎Hayama Emiko, Nakanishi Toshio|
|概要||[Introduction] Developmental changes in the contractile system of blood vessels such as ductus arteriosus (DA), pulmonary artery (PA) and aorta (Ao) have not been investigated extensively.
[Purpose] We assessed developmental changes in expression of genes which regulate vasoconstriction of the fetal blood vessels.
[Methods] DA, PA and Ao were taken from fetuses at 21, 27, 30 days of gestation (full term 31 days) and 2-day-old newborn rabbits. Total RNAs of DA, PA and Ao were isolated from pooled segments (74 21-day fetuses, 20 27-day fetuses, 20 30-day fetuses and 10 neonates), respectively. Target mRNA expression were quantified based on the absolute quantitative real-time PCR.
[Results] Contractile activity in smooth muscle is determined primarily by the phosphorylation state of the myosin light chain (MLC). Increased intracellular Ca2+ combined with calmodulin activates MLC kinase to phosphorylate the MLC. Expression of calmodulin and MLC kinase did not show significant difference among the vessels. Cytosolic Ca2+ is increased through Ca2+ release from sarcoplasmic reticulum (SR) and entry from extracellular space through Ca2+ channels. Expression of SR cardiac type ryanodine receptor increased as fetal maturation and was much higher than skeletal type ryanodine receptor. Expression of SR calcium store protein calsequestrin-2 in the Ao increased with development, but not in the DA and PA. It was very low in the DA and PA. Expression of SR Ca2+ pump regulator phospholamban in the PA and Ao increased with development, but not in the DA. It was very low in the DA. Expressions of SR genes differ significantly at the development stages, varied depending on the vessel, indicating differential maturity of SR in the fetal vessels. Ca2+-independent Rho/Rho-kinase pathway inhibits MLC phosphatase activity and promotes the phosphorylated state of the MLC. Expression of small GTPase RhoB and Rho kinase-1 were higher than RhoA and Rho kinase-2, respectively. Expression of these Rho/Rho kinase pathway genes was similar level in the fetal and newborn vessels. [Conclusions] In conclusion, the contraction of the premature DA, PA and Ao might be regulated predominantly by Rho/Rho kinase pathway, because of SR immaturity with poor expression of its component protein genes.