自噬缺陷在動(dòng)脈粥樣硬化中作用研究進(jìn)展

李波 戴先鵬

[摘要] 自噬是一種亞細(xì)胞過(guò)程，在溶酶體降解蛋白質(zhì)受損細(xì)胞器如線粒體過(guò)程中發(fā)揮重要作用。它對(duì)蛋白質(zhì)和線粒體功能的調(diào)節(jié)和維持細(xì)胞穩(wěn)態(tài)至關(guān)重要，而其失調(diào)則涉及多種疾病，如動(dòng)脈粥樣硬化。最近有研究表明，無(wú)論動(dòng)脈粥樣硬化斑塊中是否存在自噬刺激因子（例如活性氧、氧化脂質(zhì)和細(xì)胞因子），動(dòng)脈粥樣硬化進(jìn)展期間都存在自噬缺陷。本綜述重點(diǎn)介紹了動(dòng)脈粥樣硬化自噬缺陷的原因和后果，特別是對(duì)巨噬細(xì)胞、血管平滑肌細(xì)胞和內(nèi)皮細(xì)胞的影響，對(duì)治療動(dòng)脈粥樣硬化的自噬靶標(biāo)可能具有重要意義。

[關(guān)鍵詞] 動(dòng)脈粥樣硬化;自噬缺陷;巨噬細(xì)胞;血管平滑肌細(xì)胞;內(nèi)皮細(xì)胞;細(xì)胞凋亡;衰老

[中圖分類(lèi)號(hào)] R285 ? ? ? ? ?[文獻(xiàn)標(biāo)識(shí)碼] A ? ? ? ? ?[文章編號(hào)] 1673-9701（2020）24-0187-06

[Abstract] Autophagy is a subcellular process that plays an important role in the process of lysosomal degradation of protein-damaged organelles， such as mitochondria. It is essential for the regulation of functions of protein and mitochondria and the maintenance of cellular homeostasis. The disorder of autophagy is related to many diseases， such as atherosclerosis. Recent studies have shown that autophagy defects exist during the progression of atherosclerosis， regardless of the presence of autophagy stimulating factors（such as reactive oxygen species， oxidized lipids and cytokines） in atherosclerotic plaques. This review focuses on the causes and consequences of autophagy defects in atherosclerosis， especially the impact on macrophages， vascular smooth muscle cells and endothelial cells， which may be of great significance for the treatment of autophagy targets for atherosclerosis.

[Key words] Atherosclerosis; Autophagy defects; Macrophages; Vascular smooth muscle cells; Endothelial cells; Apoptosis; Senescence

動(dòng)脈粥樣硬化是一種慢性炎癥性疾病，其特征是大中動(dòng)脈血管內(nèi)膜中形成含脂質(zhì)的斑塊。動(dòng)脈粥樣硬化的危險(xiǎn)因素包括高血壓、高膽固醇血癥、糖尿病、肥胖和吸煙，此外也認(rèn)為老化是導(dǎo)致這種疾病的重要因素。根據(jù)流行病學(xué)研究表明，包括心肌梗死和中風(fēng)在內(nèi)的動(dòng)脈粥樣硬化血栓性疾病的發(fā)病率和患病率與年齡呈正相關(guān)性。動(dòng)脈粥樣硬化斑塊與主動(dòng)脈瘤具有相似的病理特征，包括VSMCs衰老、ECM重塑和巨噬細(xì)胞介導(dǎo)的炎癥[1，2]，但是動(dòng)脈粥樣硬化和腹主動(dòng)脈瘤之間的關(guān)聯(lián)尚不清楚[3]。盡管應(yīng)用降膽固醇療法（他汀類(lèi)藥物）、外科手術(shù)（球囊血管成形術(shù)和支架置入術(shù)）和改變生活方式（飲食和體育鍛煉），動(dòng)脈粥樣硬化仍然是發(fā)達(dá)國(guó)家的主要死亡原因之一。……