Abstract
Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs). Here we overview the work on ERKs 1 to 2, emphasising when possible their biological activities in VSMC proliferation. It is clear from numerosus studies including our own, that ERK1/ERK2 pathway has an imoprtant role in VSMC proliferation induced by insulin (INS) and thrombin. Despite the physiological and pathophysiological importance of INS and thrombin, possible signal transduction pathways involved in INS and thrombin regulation of VSMCs proliferation remains poorly understood. Thus, this review examines recent findings in signalling mechanisms involved in INS and thrombin- triggered VSMCs proliferation with particular emphasis on ERK1/2 signalling pathways. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.
Keywords: INS, thrombin, ERK1/2, VSMC, proliferation, Akt, MAPK, PDGF, atherosclerosis, hypertension, postangioplasty, restenosis, CARDIAC HYPERTROPHY, RTK, RhoGEFs
Current Pharmaceutical Design
Title: Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation
Volume: 16 Issue: 35
Author(s): Esma R. Isenovic, Sanja Soskic, Andreja Trpkovic, Branislava Dobutovic, Milan Popovic, Zoran Gluvic, Biljana Putnikovic and Pierre Marche
Affiliation:
Keywords: INS, thrombin, ERK1/2, VSMC, proliferation, Akt, MAPK, PDGF, atherosclerosis, hypertension, postangioplasty, restenosis, CARDIAC HYPERTROPHY, RTK, RhoGEFs
Abstract: Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs). Here we overview the work on ERKs 1 to 2, emphasising when possible their biological activities in VSMC proliferation. It is clear from numerosus studies including our own, that ERK1/ERK2 pathway has an imoprtant role in VSMC proliferation induced by insulin (INS) and thrombin. Despite the physiological and pathophysiological importance of INS and thrombin, possible signal transduction pathways involved in INS and thrombin regulation of VSMCs proliferation remains poorly understood. Thus, this review examines recent findings in signalling mechanisms involved in INS and thrombin- triggered VSMCs proliferation with particular emphasis on ERK1/2 signalling pathways. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.
Export Options
About this article
Cite this article as:
R. Isenovic Esma, Soskic Sanja, Trpkovic Andreja, Dobutovic Branislava, Popovic Milan, Gluvic Zoran, Putnikovic Biljana and Marche Pierre, Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation, Current Pharmaceutical Design 2010; 16 (35) . https://dx.doi.org/10.2174/138161210794454987
DOI https://dx.doi.org/10.2174/138161210794454987 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
The Proteomic Approach in the Development of Prognostic Biomarkers in Atherothrombosis
Recent Patents on Cardiovascular Drug Discovery Selenium and Cardiovascular Surgery: An Overview
Current Drug Safety Efficacy of Zofenopril Alone or in Combination with Hydrochlorothiazide in Patients with Kidney Dysfunction
Current Clinical Pharmacology Neuropeptide/Receptor Expression and Plasticity in Micturition Pathways
Current Pharmaceutical Design Endothelial Colony Forming Capacity is Related to C-Reactive Protein Levels in Healthy Subjects
Current Neurovascular Research Oxidative Stress Drivers and Modulators in Obesity and Cardiovascular Disease: From Biomarkers to Therapeutic Approach
Current Medicinal Chemistry Targeted Therapies in Solid Tumours: Pinpointing the Tumours Achilles Heel
Current Pharmaceutical Design Interrelationship Between Periapical Lesion and Systemic Metabolic Disorders
Current Pharmaceutical Design The c-Met Inhibitors: A New Class of Drugs in the Battle Against Advanced Nonsmall- Cell Lung Cancer
Current Pharmaceutical Design Function and Pharmacology of Spinally-Projecting Sympathetic Pre-Autonomic Neurones in the Paraventricular Nucleus of the Hypothalamus
Current Neuropharmacology Angiotensin II-Induced Signaling Pathways in Diabetes
Current Diabetes Reviews Neurohormonal Activation in Ischemic Stroke: Effects of Acute Phase Disturbances on Long-Term Mortality
Current Neurovascular Research Anti-VEGF Anticancer Drugs: Mind the Hypertension
Recent Advances in Cardiovascular Drug Discovery (Discontinued) Data Science Approaches to Pharmacogenetics
Current Molecular Medicine Biomarkers of Atrial Fibrillation in Metabolic Syndrome
Current Medicinal Chemistry PET Imaging and Coronary Circulatory Function: Non-Invasive Mechanistic Insights and Cardiovascular Prognosis
Current Cardiology Reviews Novel Coronavirus Disease 2019 (COVID-19) Current Update: Perspective on Epidemiology, Diagnosis, Drug Targets and Vaccines
Coronaviruses Editorial (Thematic Issue: G-protein Coupled Receptors in Vascular Biology: Implication in Health and Disease)
Current Vascular Pharmacology Consequences of Secondary Hyperparathyroidism on Vascular Calcification and Cardiovascular Mortality: Potential Benefit of Calcimimetics
Current Drug Therapy Epinephrine and its Role in the Development of Obesity and Hypertension
Current Hypertension Reviews