Vranas S, Heinemann G K, Liu H, De Blasio M J, Owens J A, Gatford K L, Black M J
1Department of Anatomy and Developmental Biology,Monash University,Clayton,VIC,Australia.
2Robinson Research Institute and Adelaide Medical School,University of Adelaide,Adelaide,SA,Australia.
J Dev Orig Health Dis. 2017 Oct;8(5):618-625. doi: 10.1017/S2040174417000381.
Low birth weight is associated with increased risk of cardiovascular disease in adulthood. Intrauterine growth restriction (IUGR) hearts have fewer CMs in early postnatal life, which may impair postnatal cardiovascular function and hence, explain increased disease risk, but whether the cardiomyocyte deficit persists to adult life is unknown. We therefore studied the effects of experimentally induced placental restriction (PR) on cardiac outcomes in young adult sheep. Heart size, cardiomyocyte number, nuclearity and size were measured in control (n=5) and PR (n=5) male sheep at 1 year of age. PR lambs were 36% lighter at birth (P=0.007), had 38% faster neonatal relative growth rates (P=0.001) and had 21% lighter heart weights relative to body weight as adults (P=0.024) than control lambs. Cardiomyocyte number, nuclearity and size in the left ventricle did not differ between control and PR adults; hearts of both groups contained cardiomyocytes (CM) with between one and four nuclei. Overall, cardiomyocyte number in the adult left ventricle correlated positively with birth weight but not with adult weight. This study is the first to demonstrate that intrauterine growth directly influences the complement of CM in the adult heart. Cardiomyocyte size was not correlated with cardiomyocyte number or birth weight. Our results suggest that body weight at birth affects lifelong cardiac functional reserve. We hypothesise that decreased cardiomyocyte number of low birth weight individuals may impair their capacity to adapt to additional challenges such as obesity and ageing.
低出生体重与成年后患心血管疾病的风险增加有关。宫内生长受限（IUGR）的心脏在出生后早期的心肌细胞数量较少，这可能会损害出生后的心血管功能，从而解释疾病风险增加的原因，但心肌细胞缺陷是否会持续到成年期尚不清楚。因此，我们研究了实验性诱导的胎盘受限（PR）对年轻成年绵羊心脏结局的影响。在1岁时，对对照（n = 5）和PR（n = 5）雄性绵羊的心脏大小、心肌细胞数量、核型和大小进行了测量。与对照羔羊相比，PR羔羊出生时体重轻36%（P = 0.007），新生儿相对生长速度快38%（P = 0.001），成年后相对于体重的心脏重量轻21%（P = 0.024）。对照和PR成年羊左心室的心肌细胞数量、核型和大小没有差异；两组心脏的心肌细胞（CM）都含有1至4个核。总体而言，成年左心室的心肌细胞数量与出生体重呈正相关，但与成年体重无关。这项研究首次证明宫内生长直接影响成年心脏中CM的组成。心肌细胞大小与心肌细胞数量或出生体重无关。我们的结果表明出生时的体重会影响终身心脏功能储备。我们假设低出生体重个体的心肌细胞数量减少可能会损害他们适应肥胖和衰老等额外挑战的能力。
