The aim of the research group is to explore the potential novel triggers for aggravation of vascular, valvular and bone disorders in hostile travel conditions during human spaceflight focusing on the pathology in arteries, heart valves and bone. We establish experimental models for remodeling of tissues and maladaptation known to occur as a result of heme- and hemoglobin stress in the vasculature. Pathology of organ damage and molecular mechanism of cellular responses are studied. Development of oxidative injury, mineralization, inflammation and endoplasmic reticulum stress are the main focuses, and exploration of adaptive responses including heme oxygenase, ferritin, iron metabolism and hydrogen sulfide as well as their regulatory mechanism are the major interests. The ultimate goal is to ground novel functional approaches to delay or prevent the development and progression of vascular, valvular and bone disorders that are provoked in hostile conditions.
1. Vascular calcification
- The potential role of hypoxia in vascular calcification.
- The role of osteoclast activity in vascular calcification
- Studying the effect of oxidized hemoglobin derivatives in the different cell types on gene expression and protein level. in vascular calcification.
2. Vascular remodeling
- The potential role of endoplasmic reticulum stress in vascular remodeling
3. Valvular calcification
- Hydrogen sulfide as a potential inhibitor of valvular calcification
- Effects of slow iron releasing compound on valvular calcification
- Effects of mitochondrially targeted hydrogen sulfide on valvular calcification
4. Vascular remodeling
- Effects of the oxidized hemoglobin and oxidized hemoglobin-derived peptids on the fate of complicated lesion progression.
- Development and introduction of genetic methods for genotyping the ApoE and AMBP genes in wild type and knock-out mice in our research lab.
- Genotyping mice involved in the studies of our research group on the effect of A1M and other molecules on vascular calcification.
- Exploring genetic mutations leading to endoplasmic reticulum stress and studying the effect, the mode of action of these genetic alterations.
- Studying the effect of genetic polymorphisms in the promoter region of the heme oxygenase-1 gene on vascular calcification and atherosclerosis.
- Examine the distribution of these polymorphisms between the control group and a group of patients who underwent angioplastic operation of their arteria carotis.