UMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), UFR Sciences Exactes et Naturelles, Reims, France.
Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048, Université de Toulouse, Toulouse, France.
Front Endocrinol (Lausanne). 2022 Feb 11;13:815356. doi: 10.3389/fendo.2022.815356. eCollection 2022.
The incidence of cardiovascular diseases is increasing worldwide with the growing aging of the population. Biological aging has major influence on the vascular tree and is associated with critical changes in the morphology and function of the arterial wall together with an extensive remodeling of the vascular extracellular matrix. Elastic fibers fragmentation and release of elastin degradation products, also known as elastin-derived peptides (EDPs), are typical hallmarks of aged conduit arteries. Along with the direct consequences of elastin fragmentation on the mechanical properties of arteries, the release of EDPs has been shown to modulate the development and/or progression of diverse vascular and metabolic diseases including atherosclerosis, thrombosis, type 2 diabetes and nonalcoholic steatohepatitis. Most of the biological effects mediated by these bioactive peptides are due to a peculiar membrane receptor called elastin receptor complex (ERC). This heterotrimeric receptor contains a peripheral protein called elastin-binding protein, the protective protein/cathepsin A, and a transmembrane sialidase, the neuraminidase-1 (NEU1). In this review, after an introductive part on the consequences of aging on the vasculature and the release of EDPs, we describe the composition of the ERC, the signaling pathways triggered by this receptor, and the current pharmacological strategies targeting ERC activation. Finally, we present and discuss new regulatory functions that have emerged over the last few years for the ERC through desialylation of membrane glycoproteins by NEU1, and its potential implication in receptor transactivation.
心血管疾病的发病率随着人口老龄化的加剧在全球范围内不断上升。生物老化对血管树有重大影响，与动脉壁的形态和功能的关键变化以及血管细胞外基质的广泛重塑有关。弹性纤维的碎片化和弹性蛋白降解产物的释放，也称为弹性蛋白衍生肽（EDPs），是老年输送动脉的典型特征。除了弹性蛋白碎片化对动脉机械性能的直接影响外，EDPs 的释放已被证明可调节多种血管和代谢疾病的发展和/或进展，包括动脉粥样硬化、血栓形成、2 型糖尿病和非酒精性脂肪性肝炎。这些生物活性肽介导的大多数生物学效应归因于一种称为弹性蛋白受体复合物（ERC）的特殊膜受体。这种三聚体受体包含一种称为弹性蛋白结合蛋白的外周蛋白、保护蛋白/组织蛋白酶 A 和一种跨膜唾液酸酶，即神经氨酸酶-1（NEU1）。在这篇综述中，在介绍衰老对血管的影响和 EDPs 的释放之后，我们描述了 ERC 的组成、该受体触发的信号通路，以及针对 ERC 激活的当前药理学策略。最后，我们通过 NEU1 对膜糖蛋白的去唾液酸化以及其在受体转激活中的潜在作用，介绍并讨论了 ERC 近年来出现的新调节功能。
