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Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment
Melisa E Zeylan1, Simge Senyuz1, Pol Picón-Pagès2
1Computational Sciences and Engineering, Graduate School of Science and Engineering, Koç University, Istanbul 34450, Türkiye.
Insights
Systems biology identified key proteins and pathways in vascular cognitive impairment (VCI). Oxidative and glycative stress, linked to aging, are implicated in VCI pathogenesis, involving advanced glycation end-products (AGEs) and RAGE signaling.
Area of Science:
- Systems biology and computational approaches
- Neuroscience and cardiovascular research
- Aging and disease mechanisms
Background:
- Vascular cognitive impairment (VCI) presents as cognitive decline due to vascular factors, with unclear underlying mechanisms.
- Aging is a major VCI determinant, often involving oxidative stress.
- Understanding VCI requires investigating the interplay between cardiovascular health and cognitive function.
Purpose of the Study:
- To identify proteins and pathways associated with VCI using systems biology.
- To explore the crosstalk between cardiovascular and cognitive diseases in VCI.
- To investigate the role of oxidative and glycative stress in VCI etiology.
Main Methods:
- Application of systems biology and computational analysis.
- Prioritization of genes and proteins involved in VCI.
- Enrichment analysis of identified genes/proteins in oxidative stress pathways.
- Experimental validation of glycative stress and signaling pathways.
Main Results:
- Oxidative stress pathways are highly relevant to VCI, with prioritized genes enriched in these pathways.
- A list of potential VCI-contributing proteins was identified: DOLK, TSC1, ATP1A1, MAPK14, YWHAZ, CREB3, HSPB1, PRDX6, and LMNA.
- Experimental data indicate glycative stress, advanced glycation end-products (AGEs), and RAGE signaling contribute to VCI.
Conclusions:
- Oxidative and glycative stress are key contributors to VCI.
- AGEs, RAGE, and Notch signaling are implicated in the etiology of VCI.
- Identified proteins offer potential targets for VCI research and therapeutic strategies.
Abstract:
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.
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