ABSTRACT Lamin A, a product of the LMNA gene, is an essential nuclear envelope component in most differentiated cells. Mutations in LMNA have been linked to premature aging disorders, including Hutchinson-Gilford progeria syndrome (HGPS). HGPS is caused by progerin, an aberrant form of lamin A that leads to premature death, typically from the complications of atherosclerotic disease. A key characteristic of HGPS is a severe loss of vascular smooth muscle cells (VSMCs) in the arteries. Various mouse models of HGPS have been created, but few of them feature VSMC depletion and none develops atherosclerosis, the death-causing symptom of the disease in humans. We recently generated a mouse model that recapitulates most features of HGPS, including VSMC loss and accelerated atherosclerosis. Furthermore, by generating cell-type–specific HGPS mouse models, we have demonstrated a central role of VSMC loss in progerin-induced atherosclerosis and premature death.

中文翻译：

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血管平滑肌细胞丢失是哈钦森-吉尔福德早衰综合征加速动脉粥样硬化的基础

摘要 Lamin A 是 LMNA 基因的产物，是大多数分化细胞中必不可少的核被膜成分。LMNA 突变与早衰症有关，包括哈钦森-吉尔福德早衰综合征 (HGPS)。HGPS 是由 progerin 引起的，这是一种异常形式的 lamin A，可导致过早死亡，通常是由于动脉粥样硬化疾病的并发症。HGPS 的一个关键特征是动脉中血管平滑肌细胞 (VSMC) 的严重丢失。已经创建了各种 HGPS 小鼠模型，但其中很少有 VSMC 耗竭的特征，并且没有一个会发展为动脉粥样硬化，这是人类疾病的致死症状。我们最近生成了一个小鼠模型，该模型概括了 HGPS 的大多数特征，包括 VSMC 损失和加速的动脉粥样硬化。此外，通过生成特定于细胞类型的 HGPS 小鼠模型，