Vakili Sahar, Cao Kan
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Int J Mol Sci. 2024 Dec 18;25(24):13537. doi: 10.3390/ijms252413537.
Hutchinson-Gilford progeria syndrome (HGPS) is a pediatric condition characterized by clinical features that resemble accelerated aging. The abnormal accumulation of a toxic form of the lamin A protein known as progerin disrupts cellular functions, leading to various complications, including growth retardation, loss of subcutaneous fat, abnormal skin, alopecia, osteoporosis, and progressive joint contractures. Death primarily occurs as the result of complications from progressive atherosclerosis, especially from cardiac disease, such as myocardial infarction or heart failure, or cerebrovascular disease like stroke. Despite the availability of lonafarnib, the only US Food and Drug Administration-approved treatment for HGPS, cardiovascular complications remain the leading cause of morbidity and mortality in affected patients. Defective angiogenesis-the process of forming new blood vessels from existing ones-plays a crucial role in the development of cardiovascular disease. A recent study suggests that Angiopoietin-2 (Ang2), a pro-angiogenic growth factor that regulates angiogenesis and vascular stability, may offer therapeutic potential for the treatment of HGPS. In this review, we describe the clinical features and key cellular processes impacted by progerin and discuss the therapeutic potential of Ang2 in addressing these challenges.
哈钦森-吉尔福德早衰综合征（HGPS）是一种儿科疾病，其临床特征类似于加速衰老。一种名为早老素的有毒形式的核纤层蛋白A异常积累会破坏细胞功能，导致各种并发症，包括生长发育迟缓、皮下脂肪流失、皮肤异常、脱发、骨质疏松和进行性关节挛缩。死亡主要是由进行性动脉粥样硬化的并发症导致的，尤其是心脏病，如心肌梗死或心力衰竭，或脑血管疾病，如中风。尽管有lonafarnib（美国食品药品监督管理局批准的唯一用于治疗HGPS的药物），但心血管并发症仍然是受影响患者发病和死亡的主要原因。有缺陷的血管生成——即从现有血管形成新血管的过程——在心血管疾病的发展中起着关键作用。最近的一项研究表明，血管生成素-2（Ang2），一种调节血管生成和血管稳定性的促血管生成生长因子，可能为治疗HGPS提供治疗潜力。在这篇综述中，我们描述了早老素影响的临床特征和关键细胞过程，并讨论了Ang2在应对这些挑战方面的治疗潜力。
