Ark shell-derived peptides AWLNH (P3) and PHDL (P4) as novel inhibitors of endothelial dysfunction in Cardiovascular disease models

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-30 DOI:10.1016/j.tice.2025.103116

Chathuri Kaushalya Marasinghe , Lakshi Ayoda Dayarathne , Jae-Young Je

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引用次数: 0

Abstract

Endothelial dysfunction is a main early event in the onset of atherosclerosis and cardiovascular diseases. This study explores the ameliorating effects of ark shell-derived multifunctional peptides, AWLNH (P3) and PHDL (P4), against oxLDL-driven endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). P3 and P4 significantly improved cell viability, enhanced nitric oxide levels, and upregulated endothelial nitric oxide synthase expression while suppressing oxLDL-stimulated lectin-like oxidized low-density lipoprotein receptor-1 expression. Additionally, P3 and P4 exhibited potent antioxidant activity by lowering intracellular ROS levels and lipid peroxidation, and increasing antioxidant enzyme activity. Furthermore, P3 and P4 inhibited oxLDL-induced endothelial cell apoptosis by modulating Bax/Bcl-2 ratio and preserving mitochondrial membrane potential. Moreover, P3 and P4 mitigated vascular inflammation through downregulating intercellular adhesion molecule-1 and vascular cell adhesion molecule-1expression. Our findings showed that P3 and P4 ameliorate oxLDL-induced endothelial dysfunction, providing insights into bioactive peptide-based therapeutics in vascular therapy.

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方舟壳源肽AWLNH （P3）和PHDL （P4）作为心血管疾病模型内皮功能障碍的新抑制剂

内皮功能障碍是动脉粥样硬化和心血管疾病发病的主要早期事件。本研究探讨了方舟壳衍生的多功能肽AWLNH （P3）和PHDL （P4）对oxldl驱动的人脐静脉内皮细胞（HUVECs）内皮功能障碍的改善作用。P3和P4显著提高细胞活力，提高一氧化氮水平，上调内皮一氧化氮合酶表达，同时抑制氧化ldl刺激的凝集素样氧化低密度脂蛋白受体-1表达。此外，P3和P4通过降低细胞内ROS水平和脂质过氧化，增加抗氧化酶活性，表现出强大的抗氧化活性。此外，P3和P4通过调节Bax/Bcl-2比值，保护线粒体膜电位，抑制氧化ldl诱导的内皮细胞凋亡。此外，P3和P4通过下调细胞间粘附分子-1和血管细胞粘附分子-1的表达来减轻血管炎症。我们的研究结果表明，P3和P4改善了氧化低密度脂蛋白诱导的内皮功能障碍，为血管治疗中基于生物活性肽的治疗提供了新的见解。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.