Laboratorio de Bioquímica Aplicada, Química y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo, Perú.
Am J Physiol Heart Circ Physiol. 2024 Apr 1;326(4):H950-H970. doi: 10.1152/ajpheart.00600.2023. Epub 2024 Feb 9.
Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights ) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca uniporter (MCU) enhance Ca-dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. ) Female VSMCs have lower cytosolic Ca levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α (Ca1.2), Na-K-2Cl symporter (NKCC1), and the Na/K-ATPase. ) When compared with androgens, the influence of estrogens on Ca homeostasis, vascular tone, and incidence of vascular disease is better documented. ) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. ) Sex-dependent differences in Ca signaling mean both sexes ought to be included in experimental design.
血管内皮细胞（ECs）和血管平滑肌细胞（VSMCs）中的钙信号对于血管张力的调节至关重要。然而，细胞内钙浓度的变化通常受到性别差异的影响。此外，大量证据表明，性激素失衡导致钙信号失调，这是心血管疾病发病机制的关键因素。在这篇综述中，讨论了雌激素和雄激素对血管钙处理蛋白的影响，重点介绍了相关的基因组或非基因组分子机制。还考虑了收集数据的实验模型。该综述强调了以下几点：1. 在雌性 ECs 中，雌激素通过激活蛋白激酶 A （PKA）增加钙激活的钾通道（BKCa）和钙激活的氯离子通道（CaCC），从而降低细胞内钙水平。此外，雌激素还通过增加瞬时受体电位香草酸 4（TRPV4）和线粒体钙单向转运体（MCU）来增强 Ca 依赖性一氧化氮（NO）的产生。在雄性中，只有瞬时受体电位经典型 3（TRPC3）在这种作用中起主要作用。2. 雌性 VSMCs 由于基质相互作用分子 1（STIM1）、钙释放激活钙调制器 1（Orai1）、钙电压门控通道亚基-α（Ca1.2）、钠-钾-2 氯协同转运体（NKCC1）和钠-钾-ATP 酶的活性和表达的差异，具有比雄性更低的细胞浆钙水平。3. 与雄激素相比，雌激素对钙稳态、血管张力和血管疾病发生率的影响有更好的记录。4. 许多研究使用超生理浓度的性激素，这可能限制了结果的生理相关性。5. 钙信号的性别依赖性差异意味着在实验设计中应包括两性。
