Abstract
The mevalonate pathway synthesizes intermediates and products such as cholesterol and nonsterol isoprenoids that are crucial for cell survival and function. In the human placenta, the prenylation of proteins, rather than cholesterol synthesis, represents the main "metabolic target" of mevalonate metabolism. Major cellular functions depend on isoprenylation including proliferation, migration, metabolism and protein glycosylation that are all crucial for proper development of the embryo and the placenta. Statins are inhibitors of HMG-CoA reductase, the enzyme that catalyzes the reduction of HMG-CoA to mevalonic acid by NADPH. In vitro experiments using human placental explants suggest that statins elicit a detrimental effect on placental growth. However, animal and epidemiologic studies show no increase of fetal malformations after exposure to statins during pregnancy. Moreover, emerging evidence from mouse studies suggest that statins may be useful in preventing serious pregnancy complications like preeclampsia.
Keywords: Animal studies, mevalonate pathway, placental development, preeclampsia, pregnancy, statins.
Graphical Abstract
Current Molecular Pharmacology
Title:Statins, Mevalonate Pathway and its Intermediate Products in Placental Development and Preeclampsia
Volume: 10
Author(s): Leonardo Ermini, Martin Post and Isabella Caniggia
Affiliation:
Keywords: Animal studies, mevalonate pathway, placental development, preeclampsia, pregnancy, statins.
Abstract: The mevalonate pathway synthesizes intermediates and products such as cholesterol and nonsterol isoprenoids that are crucial for cell survival and function. In the human placenta, the prenylation of proteins, rather than cholesterol synthesis, represents the main "metabolic target" of mevalonate metabolism. Major cellular functions depend on isoprenylation including proliferation, migration, metabolism and protein glycosylation that are all crucial for proper development of the embryo and the placenta. Statins are inhibitors of HMG-CoA reductase, the enzyme that catalyzes the reduction of HMG-CoA to mevalonic acid by NADPH. In vitro experiments using human placental explants suggest that statins elicit a detrimental effect on placental growth. However, animal and epidemiologic studies show no increase of fetal malformations after exposure to statins during pregnancy. Moreover, emerging evidence from mouse studies suggest that statins may be useful in preventing serious pregnancy complications like preeclampsia.
Export Options
About this article
Cite this article as:
Ermini Leonardo, Post Martin and Caniggia Isabella, Statins, Mevalonate Pathway and its Intermediate Products in Placental Development and Preeclampsia, Current Molecular Pharmacology 2017; 10 (2) . https://dx.doi.org/10.2174/1874467209666160112123457
DOI https://dx.doi.org/10.2174/1874467209666160112123457 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Effect of Dietary Education on Cardiovascular Risk Factors in Rheumatoid Arthritis Patients
Current Rheumatology Reviews Use of Bipolar Radiofrequency Catheter Ablation in the Treatment of Cardiac Arrhythmias
Current Cardiology Reviews Inflammation in Peripheral Arterial Disease (PAD)
Current Pharmaceutical Design Aldosterone Receptor Antagonists and Cardiovascular Disease: Do We Need a Change of the Guard?
Cardiovascular & Hematological Agents in Medicinal Chemistry Assessment of Cardiac Performance with Magnetic Resonance Imaging
Current Cardiology Reviews Pharmacological manipulation of peripheral vascular resistance in special clinical situations after pediatric cardiac surgery
Current Vascular Pharmacology Catechol-O-Methyltransferase (COMT)-Mediated Methylation Metabolism of Endogenous Bioactive Catechols and Modulation by Endobiotics and Xenobiotics: Importance in Pathophysiology and Pathogenesis
Current Drug Metabolism Randomized Clinical Stroke Trials in 2006
Current Vascular Pharmacology Targeting Cyclooxygenase and Nitric Oxide Pathway Cross-Talk: A New Signal Transduction Pathway for Developing More Effective Anti- Inflammatory Drugs
Current Signal Transduction Therapy The Effect of TNFα-Inhibitors on Cardiovascular Events in Patients with Rheumatoid Arthritis: An Updated Systematic Review of the Literature
Current Rheumatology Reviews New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases
Current Medicinal Chemistry Are Sex Differences in Outcomes of Patients with ACS from Observational Registries Similar to the Findings from Randomized Clinical Trials?
Current Pharmaceutical Design Device-based Therapies for Resistant Hypertension
Current Pharmaceutical Design Puerarin: A Review on the Pharmacological Activity, Chemical Properties and Pharmacokinetics of Main Isoflavonoid
The Natural Products Journal Recent Progress in Biological Activities of Indole and Indole Alkaloids
Mini-Reviews in Medicinal Chemistry Estriol Inhibits Dermcidin Isoform-2 Induced Inflammatory Cytokine Expression Via Nitric Oxide Synthesis in Human Neutrophil
Current Molecular Medicine Clinically Relevant Extracellular-Matrix Scaffolds for Cell Transplantation and Vascular Repair
Current Vascular Pharmacology Applications of Circadian Metabolomics
Current Metabolomics Recent Valves used for Transluminal Implantation in Patients with Aortic Valve Stenosis
Recent Patents on Cardiovascular Drug Discovery Adrenal Hyperandrogenism and Polycystic Ovary Syndrome
Current Pharmaceutical Design