目的:分析铜死亡诱导剂铁氧还蛋白1(FDX1)和硫辛酸(LA)与冠状动脉粥样硬化发生及严重程度的相关性,探讨其在冠心病(CHD)发病中的作用。
方法:我们分析了我院10月进行冠状动脉造影(CAG)的226例患者的资料,2021年10月,2022年,包括47例CAG表现正常的患者(对照组)和179例轻度,中度或重度冠状动脉狭窄(CHD组)。用ELISA测定所有患者的血清FDX1和LA水平。我们还使用HE染色检查了正常和ApoE-/-小鼠主动脉的病理变化,并用天狼星红染色观察了胶原纤维沉积。免疫组化法检测FDX1和LA在主动脉中的表达和分布,RT-PCR检测心肌组织中FDX1、LIAS和ACO2mRNA的表达。
结果:与对照组患者相比,CHD患者血清FDX1和LA水平显著降低,随着冠状动脉狭窄的恶化(P<0.01)和累及的冠状动脉分支数量的增加(P<0.05),逐渐减少。血清FDX1和LA水平呈正相关(r=0.451,P<0.01),与Gensini评分呈负相关(r=-0.241和-0.273,P<0.01)。与正常小鼠相比,ApoE-/-小鼠血脂水平显著升高(P<0.01),动脉粥样硬化指数显著升高,明显增厚,脂质聚集,主动脉胶原纤维增生,并显著降低FDX1、LA、LIAS,ACO2(P<0.05)。
结论:血清FDX1和LA水平随着冠状动脉病变的加重而降低,它们的表达与高脂血症引起的冠状动脉病变有关。
OBJECTIVE: To analyze the correlation of copper death inducer ferredoxin 1 (FDX1) and lipoic acid (LA) with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease (CHD).
METHODS: We analyzed the data of 226 patients undergoing coronary artery angiography (CAG) in our hospital between October, 2021 and October, 2022, including 47 patients with normal CAG findings (control group) and 179 patients with mild, moderate or severe coronary artery stenosis (CHD group). Serum FDX1 and LA levels were determined with ELISA for all the patients. We also examined pathological changes in the aorta of normal and ApoE-/- mice using HE staining and observed collagen fiber deposition with Sirius red staining. Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta, and RT-PCR was performed to detect the expressions of FDX1, LIAS and ACO2 mRNAs in the myocardial tissues.
RESULTS: Compared with the control patients, CHD patients had significantly lower serum FDX1 and LA levels, which decreased progressively as coronary artery stenosis worsened (P < 0.01) and as the number of involved coronary artery branches increased (P < 0.05). Serum FDX1 and LA levels were positively correlated (r=0.451, P < 0.01) and they both negatively correlated with the Gensini score (r=-0.241 and -0.273, respectively; P < 0.01). Compared with normal mice, ApoE-/- mice showed significantly increased lipid levels (P < 0.01) and atherosclerosis index, obvious thickening, lipid aggregation, and collagen fiber hyperplasia in the aorta, and significantly reduced expressions of FDX1, LA, LIAS, and ACO2 (P < 0.05).
CONCLUSIONS: Serum FDX1 and LA levels decrease with worsening of coronary artery lesions, and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.