Fundamental mechanisms of atherosclerosis

Interaction between (dysfunctional) endothelial cells and (activated) inflammatory cells triggers atherosclerosis. Therefore, our research on atherosclerosis focuses on these two cell types.   

  1. The role of endothelial cells in atherogenesis.
    The traditional risk factors alter endothelial cells towards a pro-atherogenic phenotype, attracting inflammatory cells, with altered release of endothelium-derived relaxing and contracting factors, growth factors and substances that modulate platelet aggregation. Key questions are: what are the mechanisms that change the  endothelial cells towards a pro-atherogenic phenotype. How do pharmacotherapy and lifestyle interfere with these mechanisms? What gender-specific mechanisms are involved?
  2. The role of inflammatory cells in atherogenesis
    Activated circulating monocytes that infiltrate the arterial intima play an essential role in the initiation/continuation of a low grade intimal inflammation that is key in the process of atherosclerosis and development of unstable plaques and subsequent acute ischemic events. Key questions: how are circulating monocytes primed towards a pro-inflammatory phenotype? How does this affect the development of atherosclerosis? How can this be targeted by new therapies?

Risk factors for atherosclerosis

  1. Mechanism and treatment of hyperlipidemia
  2. How does inactivity result in cardiovascular injury. How can that be prevented or treated?
  3. Adrenal causes of hypertension: diagnosis, treatment and mechanisms of vascular injury

Key questions: what is the pathophysiology of cardiovascular risk factors (causes of hyperlipidemia, hypertension)? How do these risk factors mediate the atherosclerotic process (impact on endothelium and inflammatory cells)? What is the optimal diagnostic strategy to characterize hyperlipidemia and hypertension and how can this personalize the prevention of atherosclerosis? How can these preventive interventions be implemented in clinical practice, including primary care and support of patients' self-management? How do we identify women at increased risk for atherosclerosis, in relation to reproductive parameters?

Treatment of vascular damage (atherosclerosis) and prevention of organ damage

  1. What are optimal reperfusion strategies in coronary and peripheral atherosclerosis?
  2. Detection, mechanisms and prevention of ischemia-reperfusion injury (pharmacological and ischemic conditioning).
  3. Diagnostics and treatment of carotid and microvascular coronary disease

Ischemia-reperfusion injury is not only a devastating consequence of atherosclerosis. It may also trigger a pro-inflammatory state and therefore contribute to the development of atherosclerosis and unstable plaques. Key questions: Can we detect high risk plaques that pose tha patient at risk for an acute ischemic event? How can ischemia-reperfusion injury be prevented to preserve organ function? What is the impact of ischemia-reperfusion in the atherosclerotic process? What is the impact of various risk factors for atherosclerosis, including gender, on ischemia-reperfusion injury? How can recommended treatments be optimally organized and delivered in clinical practice?