This document proposes applying systems biology approaches to better understand multifactorial human diseases and co-morbidities. It involves analyzing the interactions between intrinsic genetic and extrinsic environmental factors. The study would investigate cross-interactions in regulatory pathways and metabolism of affected organs in patients with diseases like atherosclerosis and how they relate to an individual's reactivity. It would analyze platelets as sensors of the cardiovascular system and indicators of reactivity. The goals are to establish the role of reactivity in disease development, identify key regulatory factors in co-morbidities, and develop personalized treatment strategies.

1. HEALTH.2012.2.1.2-2: SYSTEMS MEDICINE:
APPLYING SYSTEMS BIOLOGY APPROACHES FOR
UNDERSTANDING MULTIFACTORIAL HUMAN
DISEASES AND THEIR CO-MORBIDITIES
Partners:
- Donetsk national medical university
Departments of Histology, Cytology and Embryology, Propaedeutics of
Internal Medicine, Department of Dermatology, Medical Biophysics,
Medical Equipment and Clinical Informatics
-Laboratory of fundamental research (Institute of Urgent and
Recovery Surgery)

2. MULTIFACTORIAL HUMAN DISEASES AND
THEIR CO-MORBIDITIES
Genotype Embryonic Life Style
development
Diet, nutrients Environmental factors

3. INTRINSIC AND EXTRINSIC FACTORS INTERACTION
Various clinical manifestation Co-morbidities???

4. Immunopatholgy Endocrinological
Endocrinological Autonomic system
Autonomic system
Immunopatholgy
disturbance
disturbance dysregulacation
dysregulacation
Metabolical disturbance
Metabolical disturbance
Digestive system
Digestive system
pathology Coronary
Coronary
pathology
Atherosclerosis
Atherosclerosis diseases
diseases
Obesity
Obesity Diabetes
Diabetes
Co-morbidities of multifactorial diseases

5. Proposition
Investigation of Cross-interactions in regulatory axis and
metabolic ways of affected organs and their dependence on
individual reactivity of organism
Gene polymorphism
Cells response and resistance to different stimuli

6. PROPOSED DESIGN OF INVESTIGATION
PATIENTS WITH:
ATHEROSCLEROSIS
ANGINA. INFARCTION OF MYOCARDIUM
ISCHEMIC STROKE
PEPTIC ULCERS OF STOMACH AND DUODENUM
METHODS: Clinical Morphological
Instrumental Immunocytochemical
Laboratory Moleculo-genetic
Biochemical Biostatistics,
Immunoenzymological Neurocybernetics

7. PROPOSED DESIGN OF INVESTIGATION
Regulatory axis Network analysis Interlinks / co-morbities
in affected organ, system
Organ specific regulators
Regenerative potential State of innate and
Metabolic peculiarities adaptive immunity

8. PROPOSED MODEL FOR ANALYSIS
PLATELETS PLATELETS
Participate in: Are targets for:
- atherothrombosis - Hormones
- inflammation - Neurotransmitters
- vessels remodeling - cytokines
- reparation - chemokines
PLATELETS AS SENSORS OF CARDIOVACULAR SYSTEM AND MIRROW OF REACTIVITY
In vitro analysis of:
Aggregation Intracellular signaling systems
Sensitivity to systemic and organospecific Granules and hyaloplasm content
regulators Enzymes activity

9. EXPEXTED RESULTS
1. Establish the role and key determinants of reactivity of organism in
organospecific pattern of multifactorial diseases.
2. Detect the key regulatory factors in development, progression and risk
of co-morbid pathology associated with AS.
3. Develop the system of prognostic criteria of organospecific
manifestation of atherosclerosis.
DEVELOPMENT OF INDIVIDUALIZED
STRATEGY OF THERAPY