Current Medicinal Chemistry (v.22, #22)
Meet Our Editorial Board Member: by Gildas Bertho (2615-2615).
Editorial (Thematic Issue):Inflammation and Atherosclerosis: The Role of Novel Biomarkers (Part-I) by Gerasimos Siasos, Athanasios G. Papavassiliou, Dimitris Tousoulis (2616-2618).
Circulating Biomarkers Determining Inflammation in Atherosclerosis Progression by Gerasimos Siasos, Vicky Tsigkou, Evangelos Oikonomou, Marina Zaromitidou, Sotiris Tsalamandris, Konstantinos Mourouzis, Manolis Vavuranakis, Maria Anastasiou, Konstantinos Vlasis, Maria Limperi, Vasiliki Gennimata, John N. Boletis, Athanasios G. Papavassiliou, Dimitris Tousoulis (2619-2635).
Atherosclerosis is the main underlying pathology of cardiovascular disease and is precipitated by various hereditary and non-hereditary risk factors. Inflammation is considered an important step in the progression of atherosclerosis and involves numerous cells, mediators and cellular procedures. Therefore, a biomarker able to determine the vascular inflammatory status is imperative as the combination of inflammatory biomarkers with the classic risk factors might provide further information about atherosclerosis progression and cardiovascular risk. The identification of novel inflammatory molecules and the improvement in analytical methods allows the potential implementation of these tests in every day clinical practice. In the current article, we focus on the role of established and novel biomarkers in atherosclerosis progression and in the determination of cardiovascular risk. We also present recent data concerning the risk stratification of patients according to their inflammatory status and the possible anti-inflammatory treatment strategies.
The Role and Predictive Value of Cytokines in Atherosclerosis and Coronary Artery Disease by Dimitris Tousoulis, Evangelos K. Economou, Evangelos Oikonomou, Nikolaos Papageorgiou, Gerasimos Siasos, George Latsios, Eleni Kokkou, Kostantinos Mourouzis, Spyridon Papaioannou, Spyridon Deftereos, Michael W. Cleman, Maria Lymberi, Vasiliki Gennimata, Christodoulos Stefanadis (2636-2650).
Atherosclerosis is currently regarded as a chronic inflammatory disease that is mediated by several types of cells and molecules. Emphasis has been placed on the role of cytokines and the way they act and interact to initiate and sustain inflammation in the microenvironment of an atherosclerotic plaque. Cytokines are invariably expressed by all cells involved in the pathogenesis of atherosclerosis, act on a variety of targets exerting multiple effects and are largely responsible for the crosstalk among endothelial, smooth muscle cells, leukocytes and other vascular residing cells. In the present paper our aim is to review current information on the role of the most commonly discussed cytokines in the process of atherogenesis and to discuss the prognostic significance of these cytokines in atherosclerosis and coronary artery disease.
Vascular Inflammation and Atherosclerosis: The Role of Estrogen Receptors by Eva Kassi, Eliana Spilioti, Narjes Nasiri-Ansari, Christos Adamopoulos, Paraskevi Moutsatsou, Aggeliki Papapanagiotou, Gerasimos Siasos, Dimitris Tousoulis, Athanasios G. Papavassiliou (2651-2665).
Estrogen receptors mediate numerous favorable effects on cells and molecules implicated in vascular inflammation and atherogenic process. However, harmful effects have also been suggested. Actually, premenopausal women have a significantly lower risk for cardiovascular disease compared to postmenopausal women or age matched males while the incidence of cardiovascular disease is greater in postmenopausal than premenopausal women of the same age. The balance between the expression of ER subtypes may play an important role in the paradoxical characterization of estrogens as both beneficial and harmful. The activation of the newly discovered estrogen receptor GPR30 appears to be of great potential as therapeutic target in coronary heart disease, though the signaling mechanisms mediated GPR30 function still have not fully elucidated. The aim of this review is to summarize the current state of knowledge on the role of each estrogen receptor subtype in mediating the direct estrogen actions on different cellular components that participate in the atherosclerotic inflammatory process. We hope this knowledge will shed some light on the cause of the paradoxical characterization of estrogens as both beneficial and harmful, and advance the research in the development of specific ERagonists/ antagonists with improved benefit/risk ratio.
MicroRNAs Determining Inflammation as Novel Biomarkers and Potential Therapeutic Targets by Athanassios Kotsinas, Fragkiska Sigala, Spiros D. Garbis, Giorgos Galyfos, Konstantinos Filis, Konstantinos Vougas, Alexandros Papalampros, Elizabeth E. Johnson, Efstathios Chronopoulos, Alexandros G. Georgakilas, Vassilis G. Gorgoulis (2666-2679).
Cardiovascular diseases (CVDs) have become a predominant cause of death worldwide. Although CVDs encompass a variety of pathological conditions that affect the heart and blood vasculature, they can be classified into two major groups according to their basic pathophysiologic mechanisms, namely atherosclerosis and aneurysm formation. Increasing evidence implicates micro-RNAs (miRNAs or miRs) as vital factors both in the initiation and progression processes of CVDs. Some miRs have a promoting role in CVD development, while others have a protective role. Today, miRs have been shown to be potential biomarkers for several types of CVDs, while strategies targeting miRs are under consideration as potential tools for exploitation in therapeutic approaches for CVD treatments. In this review, we present the available data on the involvement of miRs in CVDs, focusing on their role as regulators of the inflammatory process as an initiating and driving component of CVDs.
Novel Inflammatory Biomarkers in Coronary Artery Disease: Potential Therapeutic Approaches by Konstantinos V. Voudris, Jake Chanin, Dmitriy N. Feldman, Konstantinos Charitakis (2680-2689).
Coronary artery disease constitutes the leading cause of mortality and morbidity in the modern world. Inflammation has been implicated to play a key role in the initiation and promotion of atherosclerosis, and the induction of plaque instability, possibly leading to acute coronary syndrome (ACS). This review aims to assess the clinical utility of well established (CRP) and novel inflammatory biomarkers (Homocyesteine, SAA, sCD40L, sLOX-1, IMA, MPO, PAPP-A and MMPs) in the diagnosis and outcome prediction of patients with ACS. The PubMed database was searched for reports using the terms “biomarkers”, “acute coronary syndrome”, “infarction”, “markers” and only original articles written in English were included. The diversity of novel biomarkers for coronary artery disease provides an insight of the varied pathophysiology of this disease. A better understanding of their properties and assimilation in daily clinical use is essential for optimal management and patient care in the future.
Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review by M. R. Ramis, S. Esteban, A. Miralles, Dun-Xian Tan, R. J. Reiter (2690-2711).
Oxidative damage is related to aging and a wide range of human disorders. Mitochondria are in large part responsible for free radical production and they are also main targets of the attack of these toxic molecules. The resulting deleterious effects of the damage to mitochondria can be prevented by antioxidants. Melatonin is an endogenouslyproduced indoleamine that modulates numerous functions, including mitochondria-related functions; this result from its capacity to penetrate all morphophysiological barriers and to enter all subcellular compartments due to its amphiphilic nature. Furthermore, this indoleamine and its metabolites are powerful antioxidants and scavengers of free radicals, protecting cellular membranes, the electron transport chain and mitochondrial DNA from oxidative damage. These properties may make melatonin a potent protector against a variety of free radical-related diseases. By comparison, other conventional antioxidants have less efficacy due to their limited access to the mitochondria. In recent years, research has focused on the advancement of mitochondria-targeted antioxidants, such as MitoQ (composed by the lipophilic triphenylphosphonium cation conjugated to the endogenous antioxidant coenzyme Q10) and MitoE (composed by the triphenylphosphonium cation attached to the antioxidant ?-tocopherol). Mitochondria-targeted antioxidants accumulate in several hundred-fold greater concentrations within mitochondria and protect these critical organelles from oxidative damage. Melatonin also seems to be a mitochondria-targeted antioxidant and has similar protective actions as the synthetic antioxidants. Further work is required to determine the therapeutic properties of these antioxidants in ameliorating diseases related to mitochondrial dysfunction.