Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment,Journal of Proteome Research

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Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2024-01-22 , DOI: 10.1021/acs.jproteome.3c00289
Melisa E Zeylan ₁ , Simge Senyuz ₁ , Pol Picón-Pagès ₂ , Anna García-Elías ₂ , Marta Tajes ₂ , Francisco J Muñoz ₂ , Baldomero Oliva ₃ , Jordi Garcia-Ojalvo ₄ , Eduard Barbu ₅ , Raul Vicente ₅ , Stanley Nattel ₆ , Angel Ois ₇ , Albert Puig-Pijoan ₇ , Ozlem Keskin ₈ , Attila Gursoy ₉

Affiliation

Computational Sciences and Engineering, Graduate School of Science and Engineering, Koç University, Istanbul 34450, Türkiye.
Laboratory of Molecular Physiology, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona 08002, Spain.
Laboratory of Structural Bioinformatics (GRIB), Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona 08002, Spain.
Laboratory of Dynamical Systems Biology, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona 08002, Spain.
Institute of Computer Science, University of Tartu, Tartu, 50090, Estonia.
Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Germany; IHU LIRYC and Fondation Bordeaux Université, Bordeaux 33000, France.
Department of Neurology, Hospital Del Mar. Hospital Del Mar - Medical Research Institute and Universitat Pompeu Fabra, Barcelona 08003, Spain.
Department of Chemical and Biological Engineering, Koç University, Istanbul 34450, Türkiye.
Department of Computer Engineering, Koç University, Istanbul 34450, Türkiye.

One of the primary goals of systems medicine is the detection of putative proteins and pathways involved in disease progression and pathological phenotypes. Vascular cognitive impairment (VCI) is a heterogeneous condition manifesting as cognitive impairment resulting from vascular factors. The precise mechanisms underlying this relationship remain unclear, which poses challenges for experimental research. Here, we applied computational approaches like systems biology to unveil and select relevant proteins and pathways related to VCI by studying the crosstalk between cardiovascular and cognitive diseases. In addition, we specifically included signals related to oxidative stress, a common etiologic factor tightly linked to aging, a major determinant of VCI. Our results show that pathways associated with oxidative stress are quite relevant, as most of the prioritized vascular cognitive genes and proteins were enriched in these pathways. Our analysis provided a short list of proteins that could be contributing to VCI: DOLK, TSC1, ATP1A1, MAPK14, YWHAZ, CREB3, HSPB1, PRDX6, and LMNA. Moreover, our experimental results suggest a high implication of glycative stress, generating oxidative processes and post-translational protein modifications through advanced glycation end-products (AGEs). We propose that these products interact with their specific receptors (RAGE) and Notch signaling to contribute to the etiology of VCI.

中文翻译：

心血管和认知疾病的共享蛋白质和途径：与血管认知障碍的关系

系统医学的主要目标之一是检测与疾病进展和病理表型有关的推定蛋白质和途径。血管性认知障碍（VCI）是一种异质性疾病，表现为血管因素引起的认知障碍。这种关系背后的确切机制尚不清楚，这给实验研究带来了挑战。在这里，我们应用系统生物学等计算方法，通过研究心血管疾病和认知疾病之间的相互影响来揭示和选择与 VCI 相关的相关蛋白质和通路。此外，我们还特别纳入了与氧化应激相关的信号，氧化应激是与衰老密切相关的常见病因，也是 VCI 的主要决定因素。我们的结果表明，与氧化应激相关的途径非常相关，因为大多数优先血管认知基因和蛋白质都富含在这些途径中。我们的分析提供了可能导致 VCI 的蛋白质的简短列表：DOLK、TSC1、ATP1A1、MAPK14、YWHAZ、CREB3、HSPB1、PRDX6 和 LMNA。此外，我们的实验结果表明糖化应激的高度影响，通过高级糖基化终产物（AGE）产生氧化过程和翻译后蛋白质修饰。我们认为这些产品与其特定受体 (RAGE) 和 Notch 信号传导相互作用，从而有助于 VCI 的病因学。

更新日期：2024-01-22

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