Vascular aging, a common pathogenesis of senile chronic diseases, significantly increases morbidity and mortality in older adults; its intricate cellular and molecular mechanisms necessitate further investigation. Lumican (LUM) and integrin α2β1 are profibrotic extracellular matrix proteins and vital cell regulatory receptors, respectively. However, their roles in vascular aging remain unclear. This study sought to elucidate the connection between LUM and vascular aging as well as the biological mechanism of LUM/integrin α2β1 in this process. Using an enzyme-linked immunosorbent assay, we discovered that plasma LUM was elevated in vascular aging individuals and was positively correlated with brachial-ankle pulse wave velocity. Additionally, immunohistochemical and Western blot analyses confirmed LUM upregulation in arteries of older adults and aged mice, as well as in senescent vascular smooth cells (VSMCs). Wild-type and LUM semiknockout (Lum−/+) mice, along with primary VSMCs extracted from these mice, were exposed to angiotensin II to induce a stress-induced senescence model. LUM semiknockout mitigated angiotensin II-induced arteriosclerosis, hypertension, vascular aging, and remodeling in mice. Both in vitro and in vivo studies revealed that LUM deficiency suppressed p53, p21, collagen 1, and collagen 3 upregulation and synthetic phenotype formation in VSMCs stimulated by angiotensin II. Treating VSMCs with an integrin α2β1 antagonist reversed the aforementioned changes triggered by LUM proteins. Briefly, LUM functions as a potential marker and risk factor for vascular aging and promotes pathological changes by affecting integrin α2β1 in VSMCs. This study introduces a novel molecular target for the early diagnosis and treatment of vascular aging and age-related vascular diseases.

中文翻译：

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Lumican 既是一种新的危险因素，也是血管衰老的潜在血浆生物标志物，能够通过与整合素 α2β 相互作用促进血管平滑细胞衰老1


血管衰老是老年慢性病的常见发病机制，显著增加老年人的发病率和死亡率;其错综复杂的细胞和分子机制需要进一步研究。Lumican （LUM） 和整合素 α2β1 分别是促纤维化细胞外基质蛋白和重要的细胞调节受体。然而，它们在血管衰老中的作用仍不清楚。本研究旨在阐明 LUM 与血管衰老之间的联系，以及 LUM/整合素 α2β1 在此过程中的生物学机制。使用酶联免疫吸附测定，我们发现血管衰老个体的血浆 LUM 升高，并且与肱踝脉搏波速度呈正相关。此外，免疫组织化学和蛋白质印迹分析证实了老年人和老年小鼠动脉以及衰老血管平滑细胞 （VSMC） 中 LUM 上调。野生型和 LUM 半敲除 （Lum - / +） 小鼠以及从这些小鼠中提取的原代 VSMC 暴露于血管紧张素 II 以诱导应激诱导的衰老模型。LUM semiknockout 减轻了血管紧张素 II 诱导的小鼠动脉硬化、高血压、血管衰老和重塑。体外和体内研究表明，LUM 缺陷抑制了血管紧张素 II 刺激的 VSMC 中 p53、p21、胶原蛋白 1 和胶原蛋白 3 的上调和合成表型的形成。用整合素 α2β1 拮抗剂治疗 VSMC 逆转了上述由 LUM 蛋白触发的变化。简而言之，LUM 作为血管衰老的潜在标志物和危险因素，并通过影响 VSMC 中的整合素 α2β1 促进病理变化。 本研究引入了一种新的分子靶点，用于血管衰老和年龄相关血管疾病的早期诊断和治疗。