Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA.
Medical Physiology, College of Medicine, Texas A&M Health Science Center, Bryan, TX, USA.
Curr Atheroscler Rep. 2024 Sep;26(9):463-483. doi: 10.1007/s11883-024-01223-5. Epub 2024 Jul 3.
Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption.
Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.
重度抑郁症(MDD)的特征是持续存在疲劳、对活动缺乏兴趣、悲伤和无价值感等症状。MDD 常与心血管疾病(CVD)共存,但这些疾病之间的确切联系尚不清楚。本综述探讨了导致 MDD 和 CVD 发展的因素,包括遗传、表观遗传、血小板激活、炎症、下丘脑-垂体-肾上腺(HPA)轴激活、内皮细胞(EC)功能障碍和血脑屏障(BBB)破坏。
膜相关鸟苷酸激酶 WW 和 PDZ 结构域蛋白 1(MAGI-1)中的单核苷酸多态性(SNPs)与神经质和包括 MDD 在内的精神疾病有关。MAGI-1 中的 SNPs 也与慢性炎症性疾病有关,如自发性肾小球硬化、乳糜泻、溃疡性结肠炎和克罗恩病。在克罗恩病和溃疡性结肠炎患者的结肠上皮样本中观察到 MAGI-1 的表达增加。MAGI-1 还在调节小鼠 EC 激活和动脉粥样硬化中发挥作用,并且是甲型流感病毒(IAV)感染、内质网应激诱导的 EC 凋亡和凝血酶诱导的 EC 通透性所必需的。尽管在人类疾病中研究较少;但有证据表明,MAGI-1 可能在将 CVD 和 MDD 联系起来方面发挥作用。因此,进一步研究 MAG-1 阐明其在这些疾病中的潜在作用是有必要的。