Kapelouzou Alkistis, Geronikolou Styliani, Lidoriki Irene, Kontogiannis Christos, Kaklamanis Loukas, Tsourelis Loukas, Cokkinos Dennis V
Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
1st Department of Surgery, School of Medicine, National and Kapodistrian University of Athens, Laiko Hospital, 11527 Athens, Greece.
Biology (Basel). 2023 Feb 22;12(3):347. doi: 10.3390/biology12030347.
Degenerative Aortic Stenosis (DAS) is a common disease that causes substantial morbidity and mortality worldwide, especially in the older population. Our aim was to further investigate novel serum and tissue biomarkers to elucidate biological processes involved in this entity.
We evaluated the expression of six biomarkers significantly involved in cardiovascular pathology, i.e., irisin, periostin, osteoglycin, interleukin 18, high mobility group box 1 and proprotein convertase subtilisin/kexin type 9 in the serum at the protein level, and in the tissue at both the protein and mRNA levels of patients with AS (N = 60). Five normal valves obtained after transplantation from hearts of patients with idiopathic dilated cardiomyopathy were also studied. Serum measurements were also performed in 22 individuals without valvular disease who served as controls (C).
Higher levels of all factors were found in DAS patients' serum than in normal C. IHC and PCR mRNA tissue analysis showed the presence of all biomarkers in the aortic valve cusps with DAS, but no trace of PCR mRNA was found in the five transplantation valves. Moreover, periostin serum levels correlated significantly with IHC and mRNA tissue levels in AS patients.
We showed that six widely prevalent biomarkers affecting the atherosclerotic process were also involved in DAS, suggesting a strong osteogenic and pro-inflammatory profile, indicating that aortic valve calcification is a multifactorial biological process.
退行性主动脉瓣狭窄（DAS）是一种常见疾病，在全球范围内导致大量发病和死亡，尤其是在老年人群中。我们的目的是进一步研究新的血清和组织生物标志物，以阐明该疾病所涉及的生物学过程。
我们评估了六种与心血管病理密切相关的生物标志物，即鸢尾素、骨膜蛋白、骨形成蛋白、白细胞介素18、高迁移率族蛋白B1和枯草杆菌蛋白酶/kexin 9型前蛋白转化酶在60例主动脉瓣狭窄（AS）患者血清中的蛋白水平表达，以及在其组织中的蛋白和mRNA水平表达。还研究了从特发性扩张型心肌病患者心脏移植后获得的五个正常瓣膜。对22名无瓣膜疾病的个体进行血清检测，作为对照（C）。
发现DAS患者血清中所有因子的水平均高于正常对照。免疫组化（IHC）和PCR mRNA组织分析显示，DAS患者的主动脉瓣叶中存在所有生物标志物，但在五个移植瓣膜中未发现PCR mRNA痕迹。此外，骨膜蛋白血清水平与AS患者的IHC和mRNA组织水平显著相关。
我们发现六种广泛存在的影响动脉粥样硬化过程的生物标志物也与DAS有关，提示其具有强烈的成骨和促炎特征，表明主动脉瓣钙化是一个多因素的生物学过程。
