Research Center of Neurology, 80, Volokolamskoe Shosse, 125367 Moscow, Russia.
Int J Mol Sci. 2023 Mar 28;24(7):6376. doi: 10.3390/ijms24076376.
Atherosclerosis is a chronic inflammatory disease with a complex, multifactorial pathogenesis, which includes lipid metabolism alterations. miR-33a is a microRNA that plays a key role in cholesterol efflux and promotes atherosclerosis, yet its relationship with lipid markers in carotid atherosclerosis (CA) remains unclear. The objective is to evaluate possible associations between miR-33a expression and lipid biomarkers in patients with CA. This was a prospective study that included 61 patients (median age 66.0 years, 55.7% male) with evidence of CA. Lipid profile (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol) was analyzed. Extraction and quantification of miR-33a-5p/3p was performed according to protocol. Patients were further divided depending on the target LDL level (<1.8 mmol/L). Patients with CA had relatively favorable LDL levels with a median of 2.0 mmol/L. Both miR-33a-5p and miR-33a-3p levels were lower in patients with less than targeted LDL levels (37.4 and 38.3 vs. 41.8 and 42.5 respectively, < 0.05). A significant positive correlation between expression levels of miR-33a-5p/3p and degree of carotid stenosis was found (r = 0.44 and r = 0.38 respectively, < 0.05). In a univariate linear regression model miR-33a-3p/5p was positively associated with LDL cholesterol ( = 0.02). miR-33a up-regulation is associated with CA and may, in fact, be a key player by targeting cholesterol metabolism. A decrease in LDL cholesterol (<1.8 mmol/L) corresponded to lower levels of miR-33a, yet the direction and causality of this association remains unclear.
动脉粥样硬化是一种复杂的、多因素发病的慢性炎症性疾病,包括脂质代谢改变。miR-33a 是一种 miRNA,在胆固醇外排中发挥关键作用,并促进动脉粥样硬化,但它与颈动脉粥样硬化(CA)中的脂质标志物的关系尚不清楚。目的是评估 miR-33a 表达与 CA 患者脂质生物标志物之间的可能相关性。这是一项前瞻性研究,包括 61 名(中位年龄 66.0 岁,55.7%为男性)有 CA 证据的患者。分析了血脂谱(总胆固醇、甘油三酯[TG]、高密度脂蛋白[HDL]和低密度脂蛋白[LDL]胆固醇)。根据方案进行 miR-33a-5p/3p 的提取和定量。根据目标 LDL 水平(<1.8 mmol/L)进一步将患者分为两组。CA 患者的 LDL 水平相对较好,中位数为 2.0 mmol/L。目标 LDL 水平较低的患者的 miR-33a-5p 和 miR-33a-3p 水平均较低(分别为 37.4 和 38.3 与 41.8 和 42.5,<0.05)。miR-33a-5p/3p 表达水平与颈动脉狭窄程度呈显著正相关(r = 0.44 和 r = 0.38,均<0.05)。在单变量线性回归模型中,miR-33a-3p/5p 与 LDL 胆固醇呈正相关(= 0.02)。miR-33a 的上调与 CA 相关,实际上可能通过靶向胆固醇代谢发挥关键作用。LDL 胆固醇(<1.8 mmol/L)降低与 miR-33a 水平降低相关,但这种关联的方向和因果关系尚不清楚。