Monash Newborn, Monash Children's Hospital, Melbourne, Victoria, Australia.
Department of Paediatrics, Monash University, Melbourne, Victoria, Australia.
Am J Physiol Heart Circ Physiol. 2023 Jul 1;325(1):H89-H105. doi: 10.1152/ajpheart.00134.2023. Epub 2023 May 19.
Epidemiologists have long documented a higher risk of adult-onset cardiovascular diseases (CVDs) such as stroke, hypertension, and coronary artery disease, as well as mortality from circulatory causes in low birth-weight cohorts (poor in utero substrate supply). Utero-placental insufficiency and in utero hypoxemic state-induced alterations in arterial structure and compliance are important initiating factors for adult-onset hypertension. The mechanistic links between fetal growth restriction and CVD include decreased arterial wall elastin-to-collagen ratio, endothelial dysfunction, and heightened renin-angiotensin-aldosterone system (RAAS). Systemic arterial thickness on fetal ultrasound and vascular changes in placental histopathology in growth restricted cohorts indicate fetal/developmental origins of adult-onset circulatory diseases. Similar findings of impaired arterial compliance have been noticed across age groups (neonates through to adults). Such changes augment what occurs as "normal arterial aging," resulting in accelerated arterial aging. Data from animal models suggest that hypoxemia-associated vascular adaptations enacted in utero are region specific, reflecting long-term vascular pathology. In this review, we explore the influence of birthweight and prematurity on blood pressure and arterial stiffness, demonstrating impaired arterial dynamics in growth-restricted cohorts across age groups, explain how early arterial aging influences adult-onset CVDs, describe pathophysiology data from experimental models and finally, discuss interventions which may influence aging by way of altering various cellular and molecular mechanisms of arterial aging. Age-appropriate interventions which have noted efficacy include prolonged breastfeeding and high polyunsaturated fatty acids dietary intake. Targeting the RAAS seems a promising approach. New data indicate activation of sirtuin 1 and maternal resveratrol may have beneficial effects.
流行病学家长期以来记录了低出生体重队列（宫内底物供应不足）中成年后心血管疾病（CVD）如中风、高血压和冠状动脉疾病的风险增加，以及循环系统原因导致的死亡率增加。子宫胎盘功能不全和宫内低氧血症引起的动脉结构和顺应性改变是成年后高血压的重要起始因素。胎儿生长受限与 CVD 之间的机制联系包括动脉壁弹性蛋白与胶原蛋白比值降低、内皮功能障碍和肾素-血管紧张素-醛固酮系统（RAAS）升高。胎儿超声的系统动脉厚度和生长受限队列胎盘组织病理学中的血管变化表明，成人循环系统疾病存在胎儿/发育起源。在不同年龄组（新生儿到成年人）都发现了动脉顺应性受损的类似发现。这些变化加剧了“正常动脉老化”的发生，导致动脉老化加速。动物模型的数据表明，宫内低氧血症相关的血管适应是特定区域的，反映了长期的血管病理学。在这篇综述中，我们探讨了出生体重和早产对血压和动脉僵硬的影响，证明了生长受限队列在不同年龄组中动脉动力学受损，解释了早期动脉老化如何影响成人后 CVD 的发生，描述了来自实验模型的病理生理学数据，最后讨论了可能通过改变动脉老化的各种细胞和分子机制来影响衰老的干预措施。已注意到有效的干预措施包括延长母乳喂养和高多不饱和脂肪酸饮食。靶向 RAAS 似乎是一种很有前途的方法。新数据表明，SIRT1 的激活和母体白藜芦醇可能具有有益的作用。
