FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP

IF 9.2 1区医学 Q1 PERIPHERAL VASCULAR DISEASE

Angiogenesis Pub Date : 2023-03-21 DOI:10.1007/s10456-023-09872-x

Zhongjie Fu, Pia Lundgren, Aldina Pivodic, Hitomi Yagi, Jarrod C. Harman, Jay Yang, Minji Ko, Katherine Neilsen, Saswata Talukdar, Ann Hellström, Lois E. H. Smith

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引用次数: 2

Abstract

Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4 weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).

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FGF21通过线粒体脂质氧化促进I期ROP小鼠模型中的生理血管化

视网膜血管不完全的早产儿出生后早期的高血糖与潜在致盲性新生血管性早产儿视网膜病变（ROP）的风险增加有关。新生血管性ROP（II期ROP）是对出生后生理性视网膜血管发育抑制的一种代偿性但最终是病理性反应（I期ROP）。新生小鼠中抑制生理性视网膜血管生长的高血糖与全身和视网膜成纤维细胞生长因子21（FGF21）的表达降低有关。FGF21给药促进了生理性视网膜血管生长，而FGF21缺乏抑制了生理性的视网膜血管生长。FGF21增加了血清脂联素（APN）水平，APN的缺失消除了FGF21对生理性视网膜血管发育的促进作用。阻断线粒体脂肪酸氧化也消除了FGF21对延迟生理性视网膜血管生长的保护作用。临床上，发生严重新生血管性ROP（与非严重ROP相比）的早产儿在生命的前4周的总脂质摄入量较低，胃肠外摄入较多，肠内摄入较少。我们的数据表明，在充足的肠内脂质存在的情况下提高FGF21水平可能有助于预防I期视网膜病变（从而预防新生血管疾病）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Angiogenesis PERIPHERAL VASCULAR DISEASE-

CiteScore

21.90

自引率

8.20%

发文量

审稿时长

6-12 weeks

期刊介绍： Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.