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

主动脉瓣钙化是导致主动脉瓣置换术的最常见的心脏病之一。然而，目前使用越来越频繁的生物瓣膜假体在植入后会经历进行性变性，因此只有有限的保质期。众所周知，某些疾病的流行程度因性别而异。许多疾病也可根据性别表现出不同的进展。越来越多的人认为，理想的医学治疗需要针对性别的治疗。对于心血管疾病，除了动脉粥样硬化外，男性患者主动脉瓣钙化变性的发生率高于女性患者。另一方面，流行病学和临床研究表明，绝经后妇女患心血管疾病的风险明显高于绝经前妇女。此外，激素替代疗法降低了绝经后患者患心血管疾病的风险。因此，雌激素缺乏被认为是动脉粥样硬化相关疾病的主要因素，雌激素治疗在动脉粥样硬化治疗中的作用的动物研究正在进行中。然而，慢性雌激素替代疗法有许多副作用，如阴道出血、腹痛、头痛、胸痛和体重增加。在此背景下，V. Tiyerili等人的研究表明，过氧化物酶体增殖激活受体γ (PPARγ)在内皮细胞17β-雌二醇的抗炎作用中发挥重要作用。除了已知的增加脂肪生成和胰岛素敏感性的代谢功能外，已有研究表明，激活PPARγ信号通路可以减缓雌二醇缺乏引起的血管变性。因此，PPARγ激动剂如吡格列酮（PIO）可能提供一种有利的药理学方法来影响绝经后易患冠心病的妇女的动脉粥样硬化过程。吡格列酮是格列酮类药物中的一种活性成分。吡格列酮特别用于治疗2型糖尿病，可口服给药。已发表的数据表明，单独使用PIO治疗，而不是雌激素治疗，具有维持血管形态等功能的潜力。因此，本研究的问题是研究在绝经后雌激素相对缺乏的情况下发生的生物心血管假体变性是否会受到PPARγ信号通路激活的积极影响。

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.