Exploring the complex biology of the carotid atherosclerotic plaque

Abstract

Cardiovascular disease (CVD) as result of atherosclerosis is a major cause of morbidity and mortality in many societies, despite the enormous research efforts in recent decades directed at prevention and improved treatment. Atherosclerosis of blood vessels can result in life threatening health complications including stroke, myocardial infarction, aortic dissection and leg amputation. When patients suffer from atherosclerosis of the carotid artery, the disease lesion may be removed by a carotid endarterectomy procedure. The Athero-Express biobank is the largest biobank in the world in which excised carotid artery specimens and blood samples are stored together with recorded patient health data. Subsequent extensive laboratory investigations of patient specimens have caused the Athero-Express to become an exceptionally well phenotyped cohort with unique value for the investigation of atherosclerotic cardiovascular disease and carotid artery disease in specific. The aim of this thesis was to explore the complex biology of the human carotid atherosclerotic plaque in order to provide a stepping stone towards improved risk prediction and precision drug development. To this end, we leveraged the unique properties of the Athero-Express Biobank to investigate carotid plaque parameters including histology and DNA methylation in relation to systemic risk factors such as sex, genetic variation, lipid levels, medication and smoking. This has shown that integration of genotyping, epigenotyping and phenotyping of the atherosclerotic disease lesion may yield meaningful new insights in cardiovascular disease.