■心血管疾病仍然是全球主要的健康问题,动脉粥样硬化(AS)是一个重要的贡献者。易损斑块在急性心血管事件中起关键作用。Syndecan-1(SDC-1),血管内皮糖萼中的重要膜蛋白聚糖,被认为与斑块进展有关。然而,其与动脉粥样硬化斑块严重程度和易损性的确切关系尚不清楚。本研究旨在探讨SDC-1在ApoE-/-动脉粥样硬化小鼠模型中的表达及其与斑块易损性的潜在相关性。
■使用高脂饮食(HFD)和/或左颈总动脉部分结扎(PLCA),将八周大的小鼠诱导为AS模型,与食物饮食(CD)对照组。16周后,主动脉根部斑块依次为:HFD+PLCA组>HFD组>CD+PLCA组>CD组。免疫组织化学显示脂质/泡沫细胞和CD68标记的巨噬细胞在斑块中的积累增加,血管内皮生长因子(VEGF)升高,和基质金属蛋白酶-9(MMP-9)在HFD+PLCA组的斑块,随着胶原蛋白和α-SMA标记的平滑肌细胞减少,导致最高的脆弱性指数值。冷冻斑块切片的免疫组织荧光分析显示,与CD组相比,AS小鼠组SDC-1表达显著增高,两者均与斑块易损性呈正相关。血清分析表明SDC1,鞘氨醇1-磷酸(S1P)水平升高,和AS小鼠的VEGF-A,均与斑块易损性呈正相关。多变量分析确定SDC1是斑块易损性的独立预测因子。
■这项研究增强了我们对斑块易损性机制的理解,并提出SDC1作为动脉粥样硬化的潜在生物标志物。这些发现强调了解决可改变的风险因素的重要性,例如饮食和血液动力学,并建议血清SDC1作为有价值的临床标志物。最终,这些见解可能导致在对抗心血管疾病和改善患者预后方面采取更有效的策略.
UNASSIGNED: Cardiovascular disease remains a major global health concern, with atherosclerosis (AS) being a significant contributor. Vulnerable plaques play a critical role in acute cardiovascular events. Syndecan-1 (SDC-1), a vital membrane proteoglycan in the vascular endothelial glycocalyx, is believed to be associated with plaque progression. However, its precise relationship with severity and vulnerability of atherosclerotic plaque remains unclear. This study aimed to investigate SDC-1 expression and its potential correlation with plaque vulnerability in ApoE-/- atherosclerosis mouse model.
UNASSIGNED: Eight-week-old mice were induced into the AS model using a high-fat diet (HFD) and/or partial ligation of the left common carotid artery (PLCA), with a chow diet (CD) control group. After 16 weeks, plaques in the aortic root showed the following order: HFD + PLCA group > HFD group > CD + PLCA group > CD group. Immunohistochemistry revealed heightened accumulation of lipid/foam cells and CD68-labeled macrophages in the plaques, elevated vascular endothelial growth factor (VEGF), and matrix Metalloproteinase-9 (MMP-9) in the HFD + PLCA group\'s plaques, along with reduced collagen and α-SMA-labeled smooth muscle cells, resulting in the highest vulnerability index value. Immunohistofluorescence analysis of frozen plaque sections showed significantly higher SDC-1 expression in the AS mice group compared to the CD group, both positively correlated with plaque vulnerability. Serum analysis demonstrated elevated levels of SDC1, sphingosine 1-phosphate (S1P), and VEGF-A in the AS mice, all positively correlated with plaque vulnerability. Multivariate analysis identified SDC1 as an independent predictor of plaque vulnerability.
UNASSIGNED: This study enhances our understanding of plaque vulnerability mechanisms and presents SDC1 as a potential biomarker for atherosclerosis. These findings underscore the importance of addressing modifiable risk factors, such as diet and hemodynamics and suggest the utility of serum SDC1 as a valuable clinical marker. Ultimately, these insights may lead to more effective strategies in combating cardiovascular diseases and improving patient outcomes.