The Interdependency and Co-Regulation of the Vitamin D and Cholesterol Metabolism
Tara Warren,
Roisin McAllister,
Amy Morgan,
Taranjit Singh Rai,
Victoria McGilligan,
Matthew Ennis,
Christopher Page,
Catriona Kelly,
Aaron Peace,
Bernard M. Corfe,
Mark Mc Auley,
Steven Watterson
Affiliations
Tara Warren
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Roisin McAllister
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Amy Morgan
Department of Chemical Engineering, Faculty of Science & Engineering, University of Chester, Parkgate Road, Chester CH1 4BJ, UK
Taranjit Singh Rai
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Victoria McGilligan
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Matthew Ennis
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Christopher Page
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Catriona Kelly
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Aaron Peace
Cardiology Unit, Western Health and Social Care Trust, Altnagelvin Regional Hospital, Derry BT47 6SB, UK
Bernard M. Corfe
Human Nutrition Research Centre, Institute of Cellular Medicine, William Leech Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
Mark Mc Auley
Department of Chemical Engineering, Faculty of Science & Engineering, University of Chester, Parkgate Road, Chester CH1 4BJ, UK
Steven Watterson
Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK
Vitamin D and cholesterol metabolism overlap significantly in the pathways that contribute to their biosynthesis. However, our understanding of their independent and co-regulation is limited. Cardiovascular disease is the leading cause of death globally and atherosclerosis, the pathology associated with elevated cholesterol, is the leading cause of cardiovascular disease. It is therefore important to understand vitamin D metabolism as a contributory factor. From the literature, we compile evidence of how these systems interact, relating the understanding of the molecular mechanisms involved to the results from observational studies. We also present the first systems biology pathway map of the joint cholesterol and vitamin D metabolisms made available using the Systems Biology Graphical Notation (SBGN) Markup Language (SBGNML). It is shown that the relationship between vitamin D supplementation, total cholesterol, and LDL-C status, and between latitude, vitamin D, and cholesterol status are consistent with our knowledge of molecular mechanisms. We also highlight the results that cannot be explained with our current knowledge of molecular mechanisms: (i) vitamin D supplementation mitigates the side-effects of statin therapy; (ii) statin therapy does not impact upon vitamin D status; and critically (iii) vitamin D supplementation does not improve cardiovascular outcomes, despite improving cardiovascular risk factors. For (iii), we present a hypothesis, based on observations in the literature, that describes how vitamin D regulates the balance between cellular and plasma cholesterol. Answering these questions will create significant opportunities for advancement in our understanding of cardiovascular health.
