Momin Sarah Z, Le Jacqueline T, Miranda Rajesh C
Texas A&M University School of Medicine, Bryan, TX.
Adv Drug Alcohol Res. 2023;3. doi: 10.3389/adar.2023.10924. Epub 2023 Apr 12.
Fetal alcohol spectrum disorders (FASD) are often characterized as a cluster of brain-based disabilities. Though cardiovascular effects of prenatal alcohol exposure (PAE) have been documented, the vascular deficits due to PAE are less understood, but may contribute substantially to the severity of neurobehavioral presentation and health outcomes in persons with FASD.
We conducted a systematic review of research articles curated in PubMed to assess the strength of the research on vascular effects of PAE. 40 pertinent papers were selected, covering studies in both human populations and animal models.
Studies in human populations identified cardiac defects, and defects in vasculature, including increased tortuosity, defects in basement membranes, capillary basal hyperplasia, endarteritis, and disorganized and diminished cerebral vasculature due to PAE. Preclinical studies showed that PAE rapidly and persistently results in vasodilation of large afferent cerebral arteries, but to vasoconstriction of smaller cerebral arteries and microvasculature. Moreover, PAE continues to affect cerebral blood flow into middle-age. Human and animal studies also indicate that ocular vascular parameters may have diagnostic and predictive value. A number of intervening mechanisms were identified, including increased autophagy, inflammation and deficits in mitochondria. Studies in animals identified persistent changes in blood flow and vascular density associated with endocannabinoid, prostacyclin and nitric oxide signaling, as well as calcium mobilization.
Although the brain has been a particular focus of studies on PAE, the cardiovascular system is equally affected. Studies in human populations, though constrained by small sample sizes, did link pathology in major blood vessels and tissue vasculature, including brain vasculature, to PAE. Animal studies highlighted molecular mechanisms that may be useful therapeutic targets. Collectively, these studies suggest that vascular pathology is a possible contributing factor to neurobehavioral and health problems across a lifespan in persons with a diagnosis of FASD. Furthermore, ocular vasculature may serve as a biomarker for neurovascular health in FASD.
胎儿酒精谱系障碍（FASD）通常表现为一系列基于大脑的残疾。尽管产前酒精暴露（PAE）对心血管系统的影响已有文献记载，但PAE导致的血管缺陷尚不太清楚，不过这可能在很大程度上导致了FASD患者神经行为表现的严重程度和健康结局。
我们对PubMed中收录的研究文章进行了系统综述，以评估PAE对血管影响的研究力度。共筛选出40篇相关论文，涵盖了人群研究和动物模型研究。
人群研究发现了心脏缺陷以及血管系统缺陷，包括血管迂曲增加、基底膜缺陷、毛细血管基底增生、动脉内膜炎，以及PAE导致的脑脉管系统紊乱和减少。临床前研究表明，PAE会迅速且持续地导致大脑传入大动脉血管舒张，但会使较小的脑动脉和微血管收缩。此外，PAE对脑血流量的影响会持续到中年。人和动物研究还表明，眼部血管参数可能具有诊断和预测价值。已确定了一些干预机制，包括自噬增加、炎症和线粒体缺陷。动物研究发现，与内源性大麻素、前列环素和一氧化氮信号传导以及钙动员相关的血流量和血管密度持续变化。
尽管大脑一直是PAE研究的重点，但心血管系统同样受到影响。人群研究虽然受样本量小的限制，但确实将包括脑血管在内的主要血管和组织脉管系统的病理与PAE联系起来。动物研究突出了可能成为有用治疗靶点的分子机制。总体而言，这些研究表明，血管病理可能是导致FASD患者一生神经行为和健康问题的一个因素。此外，眼部脉管系统可能作为FASD神经血管健康的生物标志物。
