動脈硬化の進展には糖尿病などの環境リスク因子が大きな影響を及ぼすが, 患者の遺伝的要因も同様に重要である。中には大変稀であるが, 動脈硬化リスクが非常に高いにもかかわらず動脈硬化の進展が全く認められない患者(抗動脈硬化患者)が存在する。そのような患者は内因性の非常に強い抗動脈硬化機構を有しているはずである。本研究では抗動脈硬化患者より作成した疾患iPS細胞を用いて内因性の抗動脈機構を解明し, 根治を目指した新規治療法開発を行いたいと考えた。
Throughout our lives, we are exposed to cellular stress, which causes age-related diseases, such as metabolic syndromes, atherosclerosis, and cancer. Although we have evolved several innate protective mechanisms from cellular stress, the damage is often cumulative and irreversible. However, in rare cases, patients with strong chronic stress such as uncontrolled diabetes, exhibit minimal organ damage, suggesting that they would have strong innate protective mechanisms. Although there are several methods of genetic analysis, including genome-wide association study and exome sequencing, the vascular protective mechanisms are still unknown. In this study, we used the endothelial cells (ECs) derived from induced pluripotent stem cells (iPSCs) of severe diabetic patients with mild atherosclerosis to examine these innate protective mechanisms and explore a molecular target, to propose a novel vascular protective mechanism against cellular stresses.
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