Vascular development in early ovine gestation: carotid smooth muscle function, phenotype, and biochemical markers
Vascular development in early ovine gestation: carotid smooth muscle function, phenotype, and biochemical markers
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DOI：
10.1152/ajpregu.00851.2006
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发表时间：
2007-07-01
影响因子：
2.8
通讯作者：
Rosenfeld, Charles R.
中科院分区：
文献类型：
--
作者：
Hutanu, Catalina;Cox, Blair E.;Rosenfeld, Charles R.
血管平滑肌(VSM)的成熟受发育调节，不同血管床的成熟程度不同。在妊娠早期，VSM功能的成熟及其对组织血流和血压调节的贡献尚不清楚。颈动脉(CA)对胎儿脑血流调节和身心健康有重要作用。我们研究了绵羊发育中期开始的CA-VSM的收缩性能、蛋白质含量和表型。从早期(妊娠88-101天)和晚期(138-150天；足月=150天)绵羊(n=14)、新生儿(6-8天；n=7)和成年(n=5)绵羊采集CA，以测量KCl、苯肾上腺素和Ang II对内皮剥脱环的作用力；细胞蛋白的变化，包括总蛋白和可溶性蛋白、肌动蛋白和肌球蛋白、肌球蛋白重链异构体(MHC)、细丝素和增殖细胞核抗原；以及血管重构。KCL和苯肾上腺素在所有年龄段均可引起年龄和剂量依赖性的收缩反应(P<；0.001)，但早期胎儿无反应。相反，血管紧张素II只在成人中引起剂量反应，与胎儿或新生动物相比，收缩能力增加了5倍以上(P<；0.001)。随着年龄的增长，收缩能力的增加与可溶性蛋白、肌动蛋白和肌球蛋白、细丝蛋白、成人平滑肌MHC-2(Sm2)和中层壁厚度的增加平行(P<；0.001)，而正常肌肉MHC-B、增殖细胞核抗原和中层细胞密度的相反减少(P<；0.001)。VSM非受体和受体介导的收缩在妊娠中期消失或明显减弱，并随年龄增加而增加，与从合成VSM表型向收缩VSM表型的转变平行，在Ang II的情况下，与向AT_1受体的转换平行。调节VSM成熟，从而调节早期发育中的血压和组织灌流的机制仍有待确定。
Vascular smooth muscle (VSM) maturation is developmentally regulated and differs between vascular beds. The maturation and contribution of VSM function to tissue blood flow and blood pressure regulation during early gestation are unknown. The carotid artery (CA) contributes to fetal cerebral blood flow regulation and well being. We studied CA VSM contractility, protein contents, and phenotype beginning in the midthird of ovine development. CAs were collected from early (88-101 day of gestation) and late (138-150 day; term = day 150) fetal (n = 14), newborn (6-8 day old; n = 7), and adult (n = 5) sheep to measure forces in endothelium-denuded rings with KCl, phenylephrine, and ANG II; changes in cellular proteins, including total and soluble protein, actin and myosin, myosin heavy chain isoforms (MHC), filamin, and proliferating cell nuclear antigen; and vascular remodeling. KCl and phenylephrine elicited age- and dose-dependent contraction responses (P < 0.001) at all ages except early fetal, which were unresponsive. In contrast, ANG II elicited dose responses only in adults, with contractility increasing greater than fivefold vs. that shown in fetal or neonatal animals (P < 0.001). Increased contractility paralleled age-dependent increases (P < 0.01) in soluble protein, actin and myosin, filamin, adult smooth muscle MHC-2 (SM2) and medial wall thickness and reciprocal decreases (P < 0.001) in nommuscle MHC-B, proliferating cell nuclear antigen and medial cellular density. VSM nonreceptor- and receptor-mediated contractions are absent or markedly attenuated in midgestation and increase age dependently, paralleling the transition from synthetic to contractile VSM phenotype and, in the case of ANG II, paralleling the switch to the AT, receptor. The mechanisms regulating VSM maturation and thus blood pressure and tisue perfusion in early development remain to b determined.