Immune-Lipid Crosstalk Research Group

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Emiel van der Vorst

Name

Emiel van der Vorst

Immune-Lipid Crosstalk Research Group

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Project description

Cardiovascular disease, in short: CVD, the leading cause of death worldwide, has been included as top health priority in EU-framework “Horizon 2020”. Atherosclerosis, a lipid-driven chronic inflammatory artery disease, has been recognized as the main underlying cause of CVD.

A highly relevant and until now fairly neglected subgroup of patients in respect to CVD are patients with chronic kidney disease, CKD.It has been clearly shown that CKD patients have a severely increased incidence of CVD, clearly demonstrated by the fact that almost half of the CKD patients die from CVD rather than from the primary kidney disease. Intriguingly, this increased CVD risk in CKD patients cannot be fully explained by the classical CVD risk factors like hypertension or dyslipidemia, suggesting the existence of CKD-specific cardiovascular risk factors. Identification of such CKD-specific risk factors and underlying disease specific pathological mechanisms will be crucial in order to develop novel diagnostic and therapeutic options.Therefore, supported by my expertise and previous results in the cardiovascular field, I aim to explore a new pathological mechanism in CKD that could contribute to this increased CKD-specific cardiovascular risk, being immune-lipid crosstalk between HDL and chemokines/chemokine-receptors in CKD.

Recently, evidence is mounting, including from my own research, that main driving factors of cardiovascular diseases, dyslipidemia and inflammation, are interdependent and that considerable crosstalk exists between these two processes. Preliminary studies led me to postulate that HDL interferes with the activity of chemokines/chemokine-receptors, thereby identifying a novel, crucial mechanism of immune-lipid crosstalk.

Complementary, also in CKD patients, it was recently demonstrated that there is an important link between uremic lipoproteins and inflammatory processes in association with increased cardiovascular risk in CKD patients. CKD patients have clear alterations in both HDL quantity and quality/composition, induced by several factors, e.g. uremic toxins or increased oxidative stress.

This makes it conceivably that CKD-modified HDL will also interfere with chemokine receptor signaling and thus influence inflammation. Combined, it would be of great interest to investigate how these CKD-modified HDL particles function as part of a disturbed immune-lipid crosstalk in CKD, creating a unique research niche.

Aim of the project

The overall objective of this research group will be the elucidation of the regulation of chemokine-receptor activity by HDL, especially by CKD-modified HDL and its functional implications in relation to increased inflammation of CKD. Ultimately, I expect to establish a novel mechanism of immune-lipid crosstalk, where chemokine/chemokine-receptor activity is influenced by HDL, which plays a crucial role in CKD-specific cardiovascular risk, thereby defining new targets for intervention.