Stephens Elizabeth H, Post Allison D, Laucirica Daniel R, Grande-Allen K Jane
Department of Bioengineering, Rice University, Houston, TX, USA.
Pediatr Dev Pathol. 2010 Nov-Dec;13(6):447-58. doi: 10.2350/09-11-0749-OA.1. Epub 2010 Jun 10.
At birth, the mechanical environment of valves changes radically as fetal shunts close and pulmonary and systemic vascular resistances change. Given that valves are reported to be mechanosensitive, we investigated remodeling induced by perinatal changes by examining compositional and structural differences of aortic and mitral valves (AVs, MVs) between 2-day-old and 3rd fetal trimester porcine valves using immunohistochemistry and Movat pentachrome staining. Aortic valve composition changed more with birth than the MV, consistent with a greater change in AV hemodynamics. At 2 days, AV demonstrated a trend of greater versican and elastin (P = 0.055), as well as greater hyaluronan turnover (hyaluronan receptor for endocytosis, P = 0.049) compared with the 3rd-trimester samples. The AVs also demonstrated decreases in proteins related to collagen synthesis and fibrillogenesis with birth, including procollagen I, prolyl 4-hydroxylase, biglycan (all P ≤ 0.005), and decorin (P = 0.059, trend). Both AVs and MVs demonstrated greater delineation between the leaflet layers in 2-day-old compared with 3rd-trimester samples, and AVs demonstrated greater saffron-staining collagen intensity, suggesting more mature collagen in 2-day-old compared with 3rd-trimester samples (each P < 0.05). The proportion of saffron-staining collagen also increased in AV with birth (P < 0.05). The compositional and structural changes that occur with birth, as noted in this study, likely are important to proper neonatal valve function. Furthermore, normal perinatal changes in hemodynamics often do not occur in congenital valve disease; the corresponding perinatal matrix maturation may also be lacking and could contribute to poor function of congenitally malformed valves.
出生时,随着胎儿分流关闭以及肺和体循环血管阻力的变化,瓣膜的力学环境发生了根本性改变。鉴于已有报道称瓣膜具有机械敏感性,我们通过免疫组织化学和Movat五色染色法,研究了2日龄猪与孕晚期猪主动脉瓣和二尖瓣(AVs、MVs)的成分和结构差异,以此来探究围产期变化所诱导的重塑过程。与二尖瓣相比,主动脉瓣成分随出生发生的变化更大,这与主动脉瓣血流动力学的更大变化相一致。在出生2天时,与孕晚期样本相比,主动脉瓣显示出多能蛋白聚糖和弹性蛋白含量增加的趋势(P = 0.055),以及透明质酸周转率更高(内吞作用的透明质酸受体,P = 0.049)。随着出生,主动脉瓣中与胶原蛋白合成和纤维形成相关的蛋白质也减少,包括前胶原蛋白I、脯氨酰4 - 羟化酶、双糖链蛋白聚糖(均P≤0.005)和核心蛋白聚糖(P = 0.059,呈趋势)。与孕晚期样本相比,2日龄的主动脉瓣和二尖瓣在小叶层之间的界限都更清晰,并且主动脉瓣显示出更深的藏红花色染色胶原蛋白强度,表明与孕晚期样本相比,2日龄时胶原蛋白更成熟(各P < 0.05)。随着出生,主动脉瓣中藏红花色染色胶原蛋白的比例也增加(P < 0.05)。本研究中所指出的出生时发生的成分和结构变化,可能对新生儿瓣膜的正常功能很重要。此外,先天性瓣膜疾病通常不会发生正常的围产期血流动力学变化;相应的围产期基质成熟可能也会缺失,这可能导致先天性畸形瓣膜功能不良。