Early Indicator of Atherosclerosis
Alteration of Inflammatory/Redox Balance as an Early Indicator of Atherosclerosis, and its Correction by the Means of Statins and Antioxidants
Tech Area / Field
3 Approved without Funding
Tbilisi State Medical University / Research Institute of Experimental and Clinical Medicine / National Center of Therapy, Georgia, Tbilisi
- Tbilisi State Medical University, Georgia, Tbilisi
- Loyola University Chicago / Loyola University Health System\nBiomed Research Foundation, USA, USA, MD, Olney\nInternational Longevity Center - USA, USA, New York\nUniversita degli Studi di Milano / Ordinario di Farmacologia, Italy, Milan\nDartmouth Medical School, USA, NH, Hanover
Project summaryProject objectives: The goal of the project is to identify the most sensitive parameters of oxidative metabolism and inflammatory markers preceding the clinical manifestation of atherosclerosis and reflecting the severity of the disease; as well as to provide evaluation of the efficacy of antioxidant therapy proposed by the project with the purpose of the treatment / prevention of atherosclerosis as compared to that of statin therapy.
Atherosclerosis is one of the biggest medical and social-economical problems throughout the world including Georgia. Moreover, atherosclerosis in Georgia tends to increasing frequency and rejuvenation of the contingent of patients. Well known diagnostic criteria of atherosclerosis (high blood cholesterol, high triglycerides, burdened family anamnesis, smoking, unbalanced diet, physical inactivity, etc.) become revealed in the period of clinical manifestation of the disease, when extensive lesions in blood vessels are irreversible though still amenable to the control. Therefore search and identification of early markers of atherosclerosis with reliable prognostic value is an urgent task for successful, timely detection of atherosclerotic alterations. It will make it possible to elaborate a strategy that would be more focused on the prevention of irreversible pathological changes and complications associated with atherosclerosis.
We assume that alteration of redox-status and the balance of pro-antiinflammatory markers does not result from atherosclerosis, but like other risk-factors chronically effecting redox system they create conditions that contribute to the development of atherosclerosis. Revelation of correlations between changes in redox- and inflammatory markers, their specificity and clinical signs of atherosclerosis will allow to identify the most sensitive and specific inpidual markers of redox-status/inflammation or their combinations as predictors and indicators of atherosclerosis development.
Numerous randomized research studies evidence that LDL-lowering statin therapy successfully limits and even reverses the development of coronary atherosclerosis. Besides lipid lowering effect statins contribute to the correction of endothelial dysfunction, inhibition of inflammatory processes, reduction of oxidative stress, stabilization of atherosclerotic plaques, though, statins fail to exert correcting effect on lowered level of HDL-cholesterol. Despite the significant decrease in death rate from cardiovascular diseases in developed countries, a substantial burden of cardiovascular disease remains in statin-treated patients. High cost of statin therapy and its restriction for the patients with liver diseases should be also taken into account. These conditions limit the area of statin application and suggest the necessity of the search for alternative ways of effective and comparatively cheap methods of atherosclerosis treatment.
Extensive volume of basic clinical and experimental research proving involvement of reactive oxygen species (ROS) in the pathogenesis of atherosclerosis suggest that antioxidant therapy could be beneficial during atherosclerosis. Though, absence of common criteria of identification of patients undergoing antioxidant treatment and as well as of control of their redox homeostasis, persity of methodologies for the assessment of oxidative stress, absence of coordinated opinion about the most sensitive inflammatory markers, as well as high specificity of the effect of various antioxidant preparations lead to discrepant results of antioxidant therapy. For the treatment of atherosclerosis we offer the complex of antioxidant preparations - vitamin E and triovit, and the preparation “phenovin” synthesized in Georgia out of phenol compounds of red grapes peel (“Sapheravi”) characterized by antioxidant, hypolipidemic, fibrinolytic, thrombolytic properties.
In the course of project implementation specific redox-parameters or their combinations, as early predictors of atherosclerosis development, will be identified in the blood of patients; There will be revealed diagnostically significant changes in one or combined redox parameters and inflammatory markers related to the severity of atherosclerosis. Analysis of the conducted research will enable us to identify and establish the tests for the determination of the most sensitive parameters of redox- and immune systems that would contribute to the diagnostics of risk, early stages and the progression of the disease. This information will certainly influence the basic understanding of changes in redox- and immune systems during atherosclerosis. It could be used in clinics for the improvement of diagnostics and prognostics of patients at risk of cardiovascular diseases and will facilitate the identification of key targets for therapeutic intervention.
If the most sensitive markers of atherosclerosis, established in the course of the research, prove to be diagnostically significant, it will demonstrate that correction of specific parameters of oxidative metabolism and inflammatory biomarkers is a key indicator of the efficacy of antioxidants used for treatment and prevention of atherosclerosis. In case of relatively high efficacy (as compared that of statins) of antioxidant treatment, proposed by the project, it will be introduced into the practice within the program of continuing medical education in Georgia as well as abroad. Introduction of new effective and comparatively cheap methodologies into the practice of treatment/prevention of atherosclerosis will increase patient inflow and commercial profit of participant organizations, as well as it will contribute to the improvement of health of broad masses of populations in Georgia and other countries with high spread of atherosclerosis. That will be beneficial for the health care system concerning economic and social aspects.
The project participants are competent in the field. Since the sixties of the last century in the NCT research works have been conducted on atherosclerosis, its etiology, pathogenesis, clinical course and different ways of treatment. Issues of timely diagnostics, in particular the most sensitive biomarkers of atherosclerosis, have been extensively studied here on the modern level. TSMU personnel has extensive experience in studying of body redox-homeostasis, including that during atherosclerosis. Intensive clinical and experimental research on the evaluation of the activity of various antioxidant preparations have been conducted in TSMU. Vegetable extracts, food additives and preparations synthesized by one of the project participants have been getting successfully through the preclinical and clinical trials and are much in demand among the population of various regions of Georgia.
The project implies direct participation of five highly qualified scientists with PhD being related to weapon and having work experience in “weapon” professional areas, as well as in the field of medical and biological research. The studies to be conducted within the framework of the project will hopefully become a subject of considerable interest of foreign specialists of many countries, and thereby will contribute to the integration of scientists from CIS with the international community. The project will provide support to the group of Georgian therapeutists, cardiologists and scientists known for their achievements. Four participants of the proposed project also participated in ISTC (G-895) project. Experience and knowledge acquired by participants in the previous project will be useful for the implementation of the present project.
Strengthening of material – technical basis in the framework of the project will enable us to conduct new significant research and prevent the leakage of qualified specialists. The opportunity of acquisition of modern equipment will enable us to expand existing knowledge, to reveal new markers of atherosclerosis and to establish new diagnostic criteria of atherosclerosis that may be used in practice throughout the world. Aforesaid fully meets the goals and tasks of ISTC.
Submitted project intends to support fundamental research for exceptionally peaceful purposes. The project is important for the future prospects as well as for the present, given that under the conditions of contemporary crisis caused by profound political-economical and ecological changes of the last decade, atherosclerosis is widespread among elderly as well as young inpiduals and it is a major cause of human morbidity and mortality throughout the world. That requires the elaboration of new methods of prevention and treatment of the disease. Therefore support to the proposed project will enrich our understanding of pathophysiology of atherosclerosis as well as it will contribute to the development of new, optimally cheap and effective methods of treatment and prevention. The project will be implemented by the means of highly sensitive modern methods complying with the requirements of contemporary scientific community (EPR spectroscopy, spectrophotometry, immune-enzyme assay, gas chromatography, polarography, radioligand method, coronarography, dopplerography, etc.).
The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.
ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.