Exploring the Effect of Fibrinogen Overexpression on Cardiomyocyte Apoptosis in Coronary Heart Disease with Blood Stasis Syndrome via the Wnt/β-catenin Pathway
GAO Lingwei
YU Yunfeng
MA Zhiyan
HU Yilei
LUO Xiaoxin
JIAN Weixiong
Abstract:Objective To investigate the mechanism by which fibrinogen(Fg)overexpression regulates the Wnt/β-catenin pathway and induces cardiomyocyte apoptosis in a rat model of coronary heart disease(CHD)with blood stasis.Methods Twenty male SD rats were divided into four groups:control group,model group,adeno-associated virus(AAV)group,and Fg group.The control group was fed a standard diet,while the other groups were subjected to a high-fat diet,intragastric administration of vitamin D3,and subcutaneous injection of isoproterenol to establish a CHD model with blood stasis syndrome.During modeling,the control and model groups received two tail vein injections of 0.9%sodium chloride solution,the AAV group received two injections of AAV empty vector,and the Fg group received two injections of AAV to overexpress the Fg gene.After modeling,electrocardiogram(ECG)and cardiac ultrasound examinations were performed.Biochemical methods were used to measure blood lipid levels,HE staining to assess aortic pathology,TUNEL to detect cardiomyocyte apoptosis,RT-qPCR to measure Wnt3a and Bcl-2-associated X protein(Bax)gene expression levels,and Western blot to detect Wnt3a,β-catenin,Bax,and Caspase-3 protein expression.Results Compared with the control group,the model,AAV,and Fg groups showed ST-segment elevation greater than 0.1 mV on ECG.Left ventricular fractional shortening(LVFS)and ejection fraction(LVEF)were significantly reduced(P<0.05).Compared with the model group,the Fg group exhibited significantly higher levels of total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)(P<0.05).Aortic pathology results revealed destruction of the three-layer arterial wall structure in the model and AAV groups,while the Fg group additionally showed intimal thickening with significant atherosclerotic plaque formation.Compared with the model group,the Fg group had a significantly higher cardiomyocyte apoptosis rate(P<0.05),elevated mRNA expression of Wnt3a and Bax(P<0.05),and significantly increased protein expression of Wnt3a,β-catenin,Bax,and Caspase-3(P<0.05).Conclusion Fg overexpression promotes cardiomyocyte apoptosis in CHD with blood stasis syndrome,and its mechanism may be related to the regulation of the Wnt/β-catenin pathway.
Keywords:Coronary heart diseaseBlood stasis syndromeFibrinogenWnt/β-cateninCardiomyocyte apoptosis
Publication Date:2026-03-28
Online Publishing Date:2026-03-31(First online date of this platform, not the publication date of the document)
Pages:7( 577-583 )
