The Interdependency and Co-Regulation of the Vitamin D and Cholesterol Metabolism

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...

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Published inCells (Basel, Switzerland) Vol. 10; no. 8; p. 2007
Main Authors Warren, Tara, McAllister, Roisin, Morgan, Amy, Rai, Taranjit Singh, McGilligan, Victoria, Ennis, Matthew, Page, Christopher, Kelly, Catriona, Peace, Aaron, Corfe, Bernard M., Mc Auley, Mark, Watterson, Steven
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 06.08.2021
MDPI
Subjects
Age
Aging
Animals
Arteriosclerosis
Atherosclerosis
Biology
Biosynthesis
Cardiovascular disease
Cardiovascular diseases
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - metabolism
Cardiovascular Diseases - prevention & control
Cholesterol
Cholesterol - blood
Cholesterol - metabolism
Cholesterol, LDL - metabolism
Dyslipidemias - drug therapy
Dyslipidemias - epidemiology
Dyslipidemias - metabolism
Heart Disease Risk Factors
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Lipid metabolism
Lipids
Lipoproteins
Low density lipoprotein
Low density lipoprotein receptors
Metabolism
Metabolites
Models, Biological
Molecular modelling
Mutation
Pathogenesis
pathway biology
Prognosis
regulation
Review
Risk Assessment
Risk factors
Statins
Supplements
Systems Biology
Vitamin D
Vitamin D - metabolism
Vitamin D - therapeutic use
Vitamin D Deficiency - drug therapy
Vitamin D Deficiency - epidemiology
Vitamin D Deficiency - metabolism
Vitamin deficiency
systems biology
cholesterol
regulation
pathway biology
vitamin D
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Abstract 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.
AbstractList 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.
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.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.
Author Peace, Aaron
Corfe, Bernard M.
Morgan, Amy
Kelly, Catriona
Page, Christopher
Ennis, Matthew
Watterson, Steven
Warren, Tara
McAllister, Roisin
McGilligan, Victoria
Rai, Taranjit Singh
Mc Auley, Mark
AuthorAffiliation 4 Human Nutrition Research Centre, Institute of Cellular Medicine, William Leech Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; Bernard.Corfe@newcastle.ac.uk
3 Cardiology Unit, Western Health and Social Care Trust, Altnagelvin Regional Hospital, Derry BT47 6SB, UK; Aaron.Peace@westerntrust.hscni.net
2 Department of Chemical Engineering, Faculty of Science & Engineering, University of Chester, Parkgate Road, Chester CH1 4BJ, UK; amy.morgan@chester.ac.uk (A.M.); m.mcauley@chester.ac.uk (M.M.A.)
1 Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK; tarawarren96@hotmail.co.uk (T.W.); rm.mcallister@ulster.ac.uk (R.M.); t.rai@ulster.ac.uk (T.S.R.); v.mcgilligan@ulster.ac.uk (V.M.); Ennis-M4@ulster.ac.uk (M.E.); Page-C7@ulster.ac.uk (C.P.); c.kelly@ulster.ac.uk (C.K.)
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– name: 2 Department of Chemical Engineering, Faculty of Science & Engineering, University of Chester, Parkgate Road, Chester CH1 4BJ, UK; amy.morgan@chester.ac.uk (A.M.); m.mcauley@chester.ac.uk (M.M.A.)
– name: 1 Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital Campus, School of Biomedical Sciences, Ulster University, Derry BT47 6SB, UK; tarawarren96@hotmail.co.uk (T.W.); rm.mcallister@ulster.ac.uk (R.M.); t.rai@ulster.ac.uk (T.S.R.); v.mcgilligan@ulster.ac.uk (V.M.); Ennis-M4@ulster.ac.uk (M.E.); Page-C7@ulster.ac.uk (C.P.); c.kelly@ulster.ac.uk (C.K.)
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/34440777$$D View this record in MEDLINE/PubMed
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Issue 8
Keywords systems biology
cholesterol
regulation
pathway biology
vitamin D
Language English
License https://creativecommons.org/licenses/by/4.0
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Snippet Vitamin D and cholesterol metabolism overlap significantly in the pathways that contribute to their biosynthesis. However, our understanding of their...
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SubjectTerms Age
Aging
Animals
Arteriosclerosis
Atherosclerosis
Biology
Biosynthesis
Cardiovascular disease
Cardiovascular diseases
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - metabolism
Cardiovascular Diseases - prevention & control
Cholesterol
Cholesterol - blood
Cholesterol - metabolism
Cholesterol, LDL - metabolism
Dyslipidemias - drug therapy
Dyslipidemias - epidemiology
Dyslipidemias - metabolism
Heart Disease Risk Factors
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Lipid metabolism
Lipids
Lipoproteins
Low density lipoprotein
Low density lipoprotein receptors
Metabolism
Metabolites
Models, Biological
Molecular modelling
Mutation
Pathogenesis
pathway biology
Prognosis
regulation
Review
Risk Assessment
Risk factors
Statins
Supplements
Systems Biology
Vitamin D
Vitamin D - metabolism
Vitamin D - therapeutic use
Vitamin D Deficiency - drug therapy
Vitamin D Deficiency - epidemiology
Vitamin D Deficiency - metabolism
Vitamin deficiency
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Title The Interdependency and Co-Regulation of the Vitamin D and Cholesterol Metabolism
URI https://www.ncbi.nlm.nih.gov/pubmed/34440777
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Volume 10
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