Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
CIBER en Enfermedades Cardiovasculares (CIBER-CV), Spain.
Cells. 2021 May 11;10(5):1157. doi: 10.3390/cells10051157.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease that recapitulates many symptoms of physiological aging and precipitates death. Patients develop severe vascular alterations, mainly massive vascular smooth muscle cell loss, vessel stiffening, calcification, fibrosis, and generalized atherosclerosis, as well as electrical, structural, and functional anomalies in the heart. As a result, most HGPS patients die of myocardial infarction, heart failure, or stroke typically during the first or second decade of life. No cure exists for HGPS, and therefore it is of the utmost importance to define the mechanisms that control disease progression in order to develop new treatments to improve the life quality of patients and extend their lifespan. Since the discovery of the HGPS-causing mutation, several animal models have been generated to study multiple aspects of the syndrome and to analyze the contribution of different cell types to the acquisition of the HGPS-associated cardiovascular phenotype. This review discusses current knowledge about cardiovascular features in HGPS patients and animal models and the molecular and cellular mechanisms through which progerin causes cardiovascular disease.
亨廷顿氏舞蹈症-早老综合征（HGPS）是一种罕见的遗传疾病，可重现许多生理衰老的症状，并导致死亡。患者会出现严重的血管改变，主要是大量的血管平滑肌细胞丧失、血管变硬、钙化、纤维化和广泛的动脉粥样硬化，以及心脏的电、结构和功能异常。因此，大多数 HGPS 患者通常在生命的第一或第二个十年死于心肌梗死、心力衰竭或中风。目前尚无治愈 HGPS 的方法，因此，定义控制疾病进展的机制至关重要，以便开发新的治疗方法来提高患者的生活质量并延长其寿命。自发现导致 HGPS 的突变以来，已经产生了几种动物模型来研究该综合征的多个方面，并分析不同细胞类型对获得 HGPS 相关心血管表型的贡献。这篇综述讨论了 HGPS 患者和动物模型的心血管特征以及 progerin 导致心血管疾病的分子和细胞机制的最新知识。
