Influence of the peroxisome proliferator-activated-receptor-γ (PPARγ) signaling pathway on the degeneration of biological cardiovascular prostheses in the context of a relative estrogen deficiency in female aortic valve prosthesis recipients

• Applicant: Dr. Yukiharu Sugimura
• Subject Area: Cardiac and Vascular Surgery ; Pharmacology
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 498824272

Calcification of the aortic valve is one of the most common heart diseases that results in aortic valve replacement. However, the biological valve prostheses that are currently being used more and more frequently are known for the fact that they experience progressive degeneration after implantation and therefore only have a limited shelf life. It is known that the prevalence of some diseases varies by gender. Many diseases can also show different progression depending on gender. It is increasingly considered that gender-specific treatment is required for ideal medical therapy. For cardiovascular diseases, it could be shown that in addition to atherosclerosis, calcifying degeneration of the aortic valve occurs more frequently in male patients than in female patients. On the other hand, epidemiological and clinical studies have shown that postmenopausal women have a significantly higher risk of cardiovascular disease than pre-menopausal women. In addition, hormone replacement therapy has reduced the risk of cardiovascular disease in postmenopausal patients. Therefore, estrogen deficiency is considered to be a major factor in atherosclerosis-associated diseases, and animal studies on the role of estrogen therapy in the treatment of atherosclerosis are an ongoing effort. However, chronic estrogen replacement therapy has many side effects such as vaginal bleeding, abdominal pain, headache, chest pain, and weight gain. In this context, a study by V. Tiyerili et al. shows that peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in the anti-inflammatory effect of 17β-estradiol in endothelial cells. In addition to its known metabolic function in increasing adipogenesis and insulin sensitivity, it has been shown that activation of the PPARγ signaling pathway can slow down the vascular degeneration caused by estradiol deficiency. Therefore, PPARγ agonists such as pioglitazone (PIO) may offer a pharmacological approach to favorably influence atherosclerotic processes in postmenopausal women prone to CHD. Pioglitazone is an active ingredient from the group of glitazones. Pioglitazone is used in particular to treat type 2 diabetes mellitus and can be administered orally. The published data suggest that PIO therapy alone - instead of estrogen therapy - has the potential for maintaining vascular morphology and the likeTherefore, the question of the present study is to investigate whether the degeneration of biological cardiovascular prostheses that occurs under postmenopausally changed conditions of relative estrogen deficiency can be positively influenced by activation of the PPARγ signaling pathway.

• DFG Programme: Research Grants
• International Connection: Japan
• Co-Investigator: Professor Dr. Payam Akhyari
• Cooperation Partner: Professor Yoshikatsu Saiki