Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Steroids. 2011 Aug;76(9):834-9. doi: 10.1016/j.steroids.2011.02.015. Epub 2011 Mar 1.
In hypertension or other forms of cardiovascular disease, the chronic activation of the renin-angiotensin-aldosterone system (RAAS) leads to dysfunction of the vasculature, including, increased vascular tone, inflammation, fibrosis and thrombosis. Cross-talk between the main mediators of the RAAS, aldosterone and angiotensin (Ang) II, participates in the development of this vascular dysfunction. Recent studies have highlighted the molecular mechanisms supporting this cross-talk in vascular smooth muscle cells (VSMCs). Some of the signaling pathways activated by the Ang II type 1 receptor (AT(1)R) are dependent on the mineralocorticoid receptor (MR) and vice versa. VSMC signaling pathways involved in migration and growth are under the control of cross-talk between aldosterone and Ang II. A synergistic mechanism leads to potentiation of signaling pathways activated by each agent. The genomic and non-genomic mechanisms activated by aldosterone cooperate with Ang II to regulate vascular tone and gene expression of pro-inflammatory and pro-fibrotic molecules. This cross-talk is dependent on the non-receptor tyrosine kinase c-Src, and on receptor tyrosine kinases, EGFR and PDGFR, and leads to activation of MAP kinases and growth, migration and inflammatory effects. These new findings will contribute to development of better treatments for conditions in which the RAAS is excessively activated.
在高血压或其他形式的心血管疾病中，肾素-血管紧张素-醛固酮系统（RAAS）的慢性激活导致血管功能障碍，包括血管张力增加、炎症、纤维化和血栓形成。RAAS 的主要介质醛固酮和血管紧张素（Ang）II 之间的串扰参与了这种血管功能障碍的发展。最近的研究强调了支持血管平滑肌细胞（VSMCs）中这种串扰的分子机制。血管紧张素 II 型 1 受体（AT(1)R）激活的一些信号通路依赖于盐皮质激素受体（MR），反之亦然。参与迁移和生长的 VSMC 信号通路受醛固酮和 Ang II 之间串扰的控制。协同机制导致每个因子激活的信号通路增强。醛固酮和 Ang II 共同激活的基因组和非基因组机制调节血管张力和促炎及促纤维化分子的基因表达。这种串扰依赖于非受体酪氨酸激酶 c-Src，以及受体酪氨酸激酶 EGFR 和 PDGFR，并导致 MAP 激酶的激活以及生长、迁移和炎症效应。这些新发现将有助于开发治疗 RAAS 过度激活的疾病的更好方法。
