Niepolski Leszek, Jęśko-Białek Szymon, Niepolska Joanna, Pendzińska Agata
Faculty of Medicine, Prince Mieszko I Medical Academy in Poznan, Bułgarska 55, 60-321 Poznan, Poland.
Faculty of Medicine, Poznan University of Medical Sciences, Fredry 10, 61-701 Poznan, Poland.
Biomedicines. 2025 Aug 15;13(8):1990. doi: 10.3390/biomedicines13081990.
Atherosclerosis is a multifactorial, chronic inflammatory disorder characterized by the progressive accumulation of plaque within the arterial wall. Recent research has highlighted the pivotal role of bioactive peptides in modulating vascular homeostasis and inflammation. Among these, salusin-α and salusin-β have emerged as critical regulators of atherogenesis. These peptides are generated via differential proteolytic processing of preprosalusin: an amino acid precursor encoded by the torsin family 2 member A gene. Despite their common origin, salusin-α and salusin-β exhibit divergent biological activities. Salusin-β promotes vascular inflammation by enhancing oxidative stress, activating the nuclear factor kappa B signaling pathway, and upregulating proinflammatory cytokines as well as adhesion molecules, and it also facilitates foam cell formation by increasing the expression of acyl-CoA/cholesterol acyltransferase 1 and scavenger receptors, thereby contributing to plaque progression. In contrast, salusin-α appears to exert protective, anti-inflammatory, and anti-atherogenic effects by increasing the expression of the interleukin-1 receptor antagonist and inhibiting key proinflammatory mediators. Additionally, these peptides modulate the proliferation of vascular smooth muscle cells and fibroblasts, with salusin-β promoting cellular proliferation and fibrosis via calcium and 3',5'-cyclic adenosine monophosphate-mediated pathways, while the role of salusin-α in these processes is less well defined. Altered plasma levels of salusins have been correlated with the presence and severity of atherosclerotic lesions, suggesting their potential as diagnostic biomarkers and therapeutic targets. This review provides a comprehensive overview of biosynthesis, tissue distribution, and dual roles of salusins in vascular inflammation and remodeling, emphasizing their significance in the pathogenesis and early detection of atherosclerotic cardiovascular disease.
动脉粥样硬化是一种多因素的慢性炎症性疾病，其特征是动脉壁内斑块逐渐积累。最近的研究强调了生物活性肽在调节血管稳态和炎症中的关键作用。其中，salusin-α和salusin-β已成为动脉粥样硬化发生的关键调节因子。这些肽是通过前体salusin的不同蛋白水解加工产生的：前体salusin是由扭转蛋白家族2成员A基因编码的氨基酸前体。尽管它们起源相同，但salusin-α和salusin-β表现出不同的生物学活性。Salusin-β通过增强氧化应激、激活核因子κB信号通路、上调促炎细胞因子和黏附分子来促进血管炎症，还通过增加酰基辅酶A/胆固醇酰基转移酶1和清道夫受体的表达促进泡沫细胞形成，从而促进斑块进展。相比之下，salusin-α似乎通过增加白细胞介素-1受体拮抗剂的表达和抑制关键促炎介质发挥保护、抗炎和抗动脉粥样硬化作用。此外，这些肽调节血管平滑肌细胞和成纤维细胞的增殖，salusin-β通过钙和3',5'-环磷酸腺苷介导的途径促进细胞增殖和纤维化，而salusin-α在这些过程中的作用尚不清楚。Salusins血浆水平的改变与动脉粥样硬化病变的存在和严重程度相关，表明它们作为诊断生物标志物和治疗靶点的潜力。本综述全面概述了salusins的生物合成、组织分布以及在血管炎症和重塑中的双重作用，强调了它们在动脉粥样硬化性心血管疾病发病机制和早期检测中的重要性。
