Department of Physiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
Cell Commun Signal. 2024 Mar 7;22(1):166. doi: 10.1186/s12964-024-01535-8.
Clinical and experimental studies have shown that the myocardial inflammatory response during pathological events varies between males and females. However, the cellular and molecular mechanisms of these sex differences remain elusive. CD73/adenosine axis has been linked to anti-inflammatory responses, but its sex-specific cardioprotective role is unclear. The present study aimed to investigate whether the CD73/adenosine axis elicits sex-dependent cardioprotection during metabolic changes and myocarditis induced by hypobaric hypoxia.
For 7 days, male and female mice received daily injections of the CD73 inhibitor adenosine 5'- (α, β-methylene) diphosphate (APCP) 10 mg/kg/day while they were kept under normobaric normoxic and hypobaric hypoxic conditions. We evaluated the effects of hypobaric hypoxia on the CD73/adenosine axis, myocardial hypertrophy, and cardiac electrical activity and function. In addition, metabolic homeostasis and immunoregulation were investigated to clarify the sex-dependent cardioprotection of the CD73/adenosine axis.
Hypobaric hypoxia-induced cardiac dysfunction and adverse remodeling were more pronounced in male mice. Also, male mice had hyperactivity of the CD73/adenosine axis, which aggravated myocarditis and metabolic shift compared to female mice. In addition, CD73 inhibition triggered prostatic acid phosphatase ectonucleotidase enzymatic activity to sustain adenosine overproduction in male mice but not in female mice. Moreover, dual inhibition prostatic acid phosphatase and CD73 enzymatic activities in male mice moderated adenosine content, alleviating glycolytic shift and proinflammatory response.
The CD73/adenosine axis confers a sex-dependent cardioprotection. In addition, extracellular adenosine production in the hearts of male mice is influenced by prostatic acid phosphatase and tissue nonspecific alkaline phosphatase.
临床和实验研究表明，在病理事件过程中，雄性和雌性之间的心肌炎症反应存在差异。然而，这些性别差异的细胞和分子机制仍不清楚。CD73/腺苷轴与抗炎反应有关，但它在性别特异性心脏保护中的作用尚不清楚。本研究旨在探讨 CD73/腺苷轴在低压缺氧引起的代谢变化和心肌炎期间是否引发性别依赖性的心脏保护作用。
在 7 天内，雄性和雌性小鼠每天接受 CD73 抑制剂腺苷 5'-(α,β-亚甲基)二磷酸（APCP）10mg/kg/天的注射，同时保持在常压低氧和低压缺氧条件下。我们评估了低压缺氧对 CD73/腺苷轴、心肌肥大和心脏电活动和功能的影响。此外，还研究了代谢稳态和免疫调节，以阐明 CD73/腺苷轴的性别依赖性心脏保护作用。
低压缺氧诱导的心脏功能障碍和不良重构在雄性小鼠中更为明显。此外，雄性小鼠 CD73/腺苷轴活性增加，与雌性小鼠相比，这加剧了心肌炎和代谢变化。此外，CD73 抑制在雄性小鼠中引发前列腺酸性磷酸酶核苷酸酶酶活性，以维持腺苷的过度产生，但在雌性小鼠中则不然。此外，在雄性小鼠中双重抑制前列腺酸性磷酸酶和 CD73 酶活性可调节腺苷含量，减轻糖酵解变化和促炎反应。
CD73/腺苷轴赋予性别依赖性心脏保护作用。此外，雄性小鼠心脏中外源腺苷的产生受前列腺酸性磷酸酶和组织非特异性碱性磷酸酶的影响。
