导致心力衰竭的心肌梗塞(MI)导致了与CVD相关的近85%的死亡。MI由冠状动脉中的斑块形成引起,这导致心肌中缺乏氧和营养。迄今为止,支架置入术是一种广泛使用的金标准技术,可通过心肌中的冠状动脉循环维持适当的血流。裸金属支架(BMS)和药物洗脱支架(DES)主要用于植入。然而,BMS和DES都可以通过在冠状动脉中沉积过多的胶原导致再狭窄来诱导新内膜形成。尚不清楚来自新内膜ECM的保藏COL1A1的位点特异性翻译后修饰(PTM)的鉴定和定量分析。应用我们的内部工作流程,我们重新分析了以前发表的质谱数据集,以全面绘制特定位点的脯氨酸-羟基化,赖氨酰羟基化,和来自新内膜ECM的COL1A1中的O-糖基化位点。此外,我们定量了9个3-羟脯氨酸(3-HyP)位点的占有率,2羟基赖氨酸位点,和COL1A1的6个赖氨酸位点上的糖基化微异质性。虽然COL1A1的总水平在DES诱导的新内膜中降低,与BMS诱导的新内膜相比,COL1A1的23-HyP位点(P872和P881)和2个HyK位点(K435和K768)的占用水平显着升高(p<0.05)。我们还发现,与BMS诱导的新内膜相比,DES诱导的新内膜中COL1A1的3个赖氨酸位点(K573,K339以及K和K849)上的O-糖基化显着升高。一起来看,我们对COL1A1的首次全面PTM分析反映了显著的部位特异性改变,这些改变可能在MI患者支架诱导的新内膜形成期间的ECM重塑中起非常重要的作用.意义:缺乏关于在支架后再狭窄过程中沉积在新内膜ECM中的胶原蛋白1的位点特异性翻译后修饰(PTM)的知识。第一次来这里,我们报道了金属支架和药物洗脱支架诱导的新内膜形成过程中COL1A1PTM水平的改变.我们的研究显示了在支架诱导的再狭窄过程中通过位点特异性胶原蛋白PTM进行的新型ECM重塑。
Myocardial infarction (MI) leading to heart failure contributes to almost 85% of deaths associated with CVDs. MI results from plaque formation in the coronary artery which leads to a lack of oxygen and nutrients in the myocardium. To date, stenting is a widely used gold-standard technique to maintain the proper blood flow through coronary circulation in the myocardium. Bare metal stents (BMS) and drug-eluting stents (DES) are majorly used in implantation. However, BMS and DES both can induce neointima formation by depositing excessive collagens in the coronary arteries leading to restenosis. Identification and quantitative analysis of site-specific post-translational modifications (PTMs) of deposited COL1A1 from neointima ECM are not known. Applying our in-house workflow, we re-analyzed a previously published mass-spectrometry data set to comprehensively map site-specific prolyl-hydroxylation, lysyl hydroxylation, and O-glycosylation sites in COL1A1 from neointima ECM. Furthermore, we quantitated the occupancy level of 9 3-hydroxyproline (3-HyP) sites, 2 hydroxylysine sites, and glycosylation
microheterogeneity on 6 lysine sites of COL1A1. Although the total level of COL1A1 was decreased in DES-induced neointima, the occupancy levels of 2 3-HyP sites (P872, and P881) and 2 HyK (K435 and K768) sites of COL1A1 were significantly (p < 0.05) elevated in DES-induced neointima compared to BMS-induced neointima. We also found O-glycosylation to be significantly elevated on 3 lysine sites (K573, K339, and K and K849) of COL1A1 in DES-induced neointima compared to BMS-induced neointima. Taken together, our first comprehensive PTM analysis of COL1A1 reflected significant site-specific alterations that may play a very important role in the ECM remodeling during stent-induced neointima formation in MI patients. SIGNIFICANCE: The knowledge about site-specific post-translational modifications (PTMs) of collagen 1 deposited in the neointima ECM during the post-stenting restenosis process is absent. Here for the first time, we report the altered levels of COL1A1 PTMs during metal stent and drug-eluting stent-induced neointima formation. Our study showcases a novel ECM remodeling through site-specific collagen PTMs during stent-induced restenosis.