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Antioxidant Therapy in Atherosclerosis

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New Antioxidants from Georgian Red Grapes and Treatment of Atherosclerosis in Postmenopausal Women

Tech Area / Field

  • MED-OTH/Other/Medicine

Status
3 Approved without Funding

Registration date
12.09.2008

Leading Institute
Tbilisi State Medical University, Georgia, Tbilisi

Collaborators

  • Universita degli Studi di Milano / Ordinario di Farmacologia, Italy, Milan\nUniversitatsklinikum Essen / Klinik für Kardiologie, Germany, Essen\nUniversity of Manitoba / Institute of Cardiovascular Sciences, Canada, MB, Winnipeg\nUniversity of Arizona / School of Medicine, USA, AZ, Tucson\nCenter for Cardiovascular Research, Czechia, Prague\nCentre for Preventive Cardiology, Czechia, Prague\nDartmouth Medical School, USA, NH, Hanover\nKlinikum Mannheim, Germany, Mannheim\nAthens Medical School, Greece, Athens

Project summary

Over the last century the world population rapidly aged, with the majority of elderly inpiduals being female. Average life expectancy of women has increased from 50 to 81.7 years, which means that a woman spends over 1/3 part of her life in a postmenopausal period. Age-depended alteration of estrogen productions is considered to be one of the widely acknowledged risk factors for the development of atherosclerosis.

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.

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 in postmenopausal women; as well as to provide evaluation of the efficacy of antioxidant therapy.

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 in postmenopausal women.

We assume that alterations of redox-status and the balance of pro-anty antyinflammatory markers do 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 (frequently encountered in postmenopausal women) 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 in postmenopausal women, given that decreased production of estrogens in postmenopausal period is one of the important pathogenetic links of atherosclerosis and contributes to its development via direct (effecting the intensity of oxidative processes) and indirect (effecting the hormonal homeostasis). 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 in postmenopausal women. It could be used in clinics for the improvement of diagnostics and prognostics of women 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 in postmenopausal women will increase patient inflow and commercial profit of participant organizations, as well as it will contribute to the improvement of health of broad female 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. Hopefully, the project results will contribute to decrease in development of atherosclerosis risk, increase in effectiveness of its prevention and treatment in Georgian population, as well as in the whole world.

Submitted project intends to support fundamental-practical 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 extensive research of age- and sex-related aspects as well of social aspects of the development of atherosclerosis, elaboration of new methods of prevention and treatment of the disease.

The project implies direct participation of 4 (four) 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. Research works of the leading scientists of the clinical part of the project 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 participation of these scientists in project will contribute to focusing their attention on the peaceful scientific trends, using their knowledge, experience and skills in health service and involving them in the development of peaceful technologies. The studies to be conducted within the framework of the project will hopefully become of considerable interest of foreign specialists of many countries, and thereby will contribute to the integration of scientists from CIS with the international community. Cooperation of highly qualified Georgian researchers with advanced foreign scientists will contribute to the integration of scientific views into international scientific views, and enrich them with their experience and knowledge. The opportunity of acquisition of modern equipment provided within the framework of the project will enable strengthening of material–technical basis to conduct new significant research and prevent the leakage of qualified specialist.

Therefore support to the proposed project will enrich our understanding of pathophysiologic characteristics of atherosclerosis in women as well as it will contribute to the development of the most sensitive tests for of its early diagnostics and of new, optimally cheap and effective methods of treatment and prevention affordable for low-income groups of populations. In this view the project has high potential for commercialization.

For this purpose, substantial effort will be made to establish business contacts with research teams and companies involved in research, development and production of antioxidant preparations of vegetable origin that are considered to be especially beneficial for the treatment of chronic diseases. 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.).


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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.

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