HBCx

2019

Cardiovascular disease (CVD) and dementia are closely intertwined, often resulting in cognitive impairment among individuals with cardiovascular or cerebrovascular conditions. Approximately one-third of dementia cases are linked to vascular injury, emphasizing that vascular cognitive impairment (VCI) is a preventable aspect of cognitive decline.

The Focus
The Heart-Brain Connection Crossroads (HBCx) consortium investigates hemodynamic alterations as reversible contributors to VCI, seeking to enhance our understanding of the connection between cardiovascular health and cognitive function.

The Research
HBCx builds upon the foundation laid by HBC1 (CVON 2012-06), which established a national network dedicated to studying, diagnosing, and treating VCI. Clinical investigations within HBC1, focusing on patients with chronic heart failure (CHF), carotid occlusive disease (COD), and clinically evident VCI, emphasized the role of hemodynamics along the heart-brain axis in VCI. These findings underscored significant associations between heart-brain connections and VCI.

The HBCx program, launched in 2019, takes a comprehensive approach by investigating hemodynamics in key cardiac conditions such as atrial fibrillation and heart failure, while also exploring vascular factors and their interplay with amyloid pathology. Moreover, HBCx considers modulating factors like age and sex. The program aims to improve early detection, identify treatable targets, and integrate the Heart-Brain Connection approach into routine care. Ultimately, the long-term vision of HBCx is to reduce VCI prevalence among CVD patients through enhanced understanding and innovative treatment strategies.

Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.

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GENIUS II

2018
The GENIUS II (Generating Evidence-Based Pharmaceutical Targets and Drugs for Atherosclerosis) consortium is dedicated to studying atherosclerosis, the primary pathological condition underlying cardiovascular diseases. The consortium aims to translate identified druggable targets for atherosclerosis intervention into clinical applications. Gender specificity is a key consideration in all our studies. Our consortium's talent program is structured to provide young researchers with insights into the opportunities and challenges of cardiovascular drug development. The Research GENIUS II research integrates knowledge of dyslipidemia and associated immune responses. Our work is organized into distinct work packages that correspond to the logical steps in drug development. Each selected target from GENIUS I is strategically incorporated into this framework. Our investigations encompass in vitro and in vivo analyses to understand mechanisms, druggability, and effects on atherosclerosis. In addition to building upon GENIUS I drug targets and leads, we leverage recent innovative advancements to identify new druggable targets within male and female atherosclerotic lesions, as well as in circulating cells. State-of-the-art molecular biology techniques, including single cell sequencing and immunophenotyping, are actively employed to dissect immunometabolic processes within atherosclerotic plaques and patients. These studies will enable us to monitor the presence of drug targets at disease sites, expediting drug design and potentially identifying gender-specific biomarkers to aid disease progression monitoring and diagnosis. Subsequent studies involve testing the efficacy of small molecules, monoclonal antibodies, and siRNA against pre-selected targets from GENIUS I. We have identified small molecules and monoclonal antibodies for five targets, which will undergo toxicity and proof-of-pharmacology studies to progress towards drug development for cardiovascular patients. We have also identified three drugs affecting primary targets from GENIUS I and are assessing their potential to reduce atherosclerotic parameters in First-In-Human clinical trials. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation. The GENIUS II consortium builds on the most promising targets identified in the GENIUS I consortium, with the goal of advancing these targets towards clinical application.
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National Network Healthy Living in a Healthy Environment

2022
Promoting a healthy lifestyle and maintaining it for a long time is crucial for the prevention of cardiovascular diseases. Lifestyle change areonly sustainable and impactful if it takes into account the context in which it occurs. The research Therefore, this netwerk will disseminate this insight widely to policymakers, researchers and everyone who contributes to promoting healthy behaviors. In this way, we can collectively achieve greater health gains when implementing potentially successful interventions. The ultimate goal is to achieve sustainable and impactful lifestyle change in the population. In the projects LIKE, BENEFIT and SUPREME NUDGE, unique expertise has been gained in the field of (1) embedding lifestyle interventions in complex systems, and (2) changing systems underlying lifestyle behavior. Within this national network, we want to disseminate and embed this expertise among researchers, practice professionals and policy makers. We will combine this expertise in the form of two toolboxes; a toolbox for practice professionals and policy makers and a toolbox for researchers. To this end, existing tools will be adapted, where necessary, to make them more widely usable. We aim to embed the toolboxes in (existing) structures and will make the toolboxes findable and disseminated through this netwerk. This network will serve as a structure for connections between stakeholders and contribute to the realization of a sustainable knowledge infrastructure. With this project we identify and create important conditions for successful further development and upscaling of innovative and sustainable ways to sustain healthy living for longer. With this we go further than many existing networks and knowledge infrastructures that focus only on 'effective interventions' but not on the structural embedding in systems or addressing the systems themselves. The origin From 2017, the Dutch Heart Foundation, together with ZonMw, invested in research by three healthy living consortia (LIKE, BENEFIT and SUPREME NUDGE). The common goal was to find new ways to achieve sustainable and impactful lifestyle change in the population. Heart Foundation and ZonMw asked the three healthy living consortia Supreme Nudge, LIKE and Benefit to join forces within this theme by using the knowledge they have gained over the past few years. Although the three consortia each had a different approach, the research leaders agreed on what is needed for lifestyle change to be truly successful: a shift in thinking about lifestyle change. Subsequently, the Dutch Heart Foundation and ZonMw provided follow-up funding to join forces and acquired knowledge in a new knowledge infrastructure.
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