Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, India.
Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, 5 Rue Blaise Pascal, 67000, Strasbourg, France.
Cell Mol Life Sci. 2023 Aug 29;80(9):271. doi: 10.1007/s00018-023-04908-3.
Chromogranin A (CHGA), a member of the granin family of proteins, has been an attractive therapeutic target and candidate biomarker for several cardiovascular, neurological, and inflammatory disorders. The prominence of CHGA stems from the pleiotropic roles of several bioactive peptides (e.g., catestatin, pancreastatin, vasostatins) generated by its proteolytic cleavage and by their wide anatomical distribution. These peptides are emerging as novel modulators of cardiometabolic diseases that are often linked to high blood cholesterol levels. However, their impact on cholesterol homeostasis is poorly understood. The dynamic nature of cholesterol and its multitudinous roles in almost every aspect of normal body function makes it an integral component of metabolic physiology. A tightly regulated coordination of cholesterol homeostasis is imperative for proper functioning of cellular and metabolic processes. The deregulation of cholesterol levels can result in several pathophysiological states. Although studies till date suggest regulatory roles for CHGA and its derived peptides on cholesterol levels, the mechanisms by which this is achieved still remain unclear. This review aims to aggregate and consolidate the available evidence linking CHGA with cholesterol homeostasis in health and disease. In addition, we also look at common molecular regulatory factors (viz., transcription factors and microRNAs) which could govern the expression of CHGA and genes involved in cholesterol homeostasis under basal and pathological conditions. In order to gain further insights into the pathways mediating cholesterol regulation by CHGA/its derived peptides, a few prospective signaling pathways are explored, which could act as primers for future studies.
嗜铬粒蛋白 A（CHGA）是颗粒蛋白家族的成员，它一直是几种心血管、神经和炎症性疾病有吸引力的治疗靶点和候选生物标志物。CHGA 的重要性源于其几种生物活性肽（如 catestatin、pancreastatin、vasostatin）的多效性作用，这些肽是由其蛋白水解切割产生的，并且具有广泛的解剖分布。这些肽正在成为调节心脏代谢疾病的新型调节剂，而心脏代谢疾病通常与高胆固醇水平有关。然而，它们对胆固醇稳态的影响知之甚少。胆固醇的动态性质及其在正常身体功能的几乎所有方面的众多作用使其成为代谢生理学的一个组成部分。胆固醇稳态的严格调节对于细胞和代谢过程的正常功能至关重要。胆固醇水平的失调可能导致几种病理生理状态。尽管迄今为止的研究表明 CHGA 及其衍生肽对胆固醇水平具有调节作用，但实现这一目标的机制仍不清楚。本综述旨在汇总和整合现有证据，将 CHGA 与健康和疾病中的胆固醇稳态联系起来。此外，我们还研究了常见的分子调节因子（即转录因子和 microRNAs），它们可以在基础和病理条件下调节 CHGA 和参与胆固醇稳态的基因的表达。为了更深入地了解 CHGA/其衍生肽介导胆固醇调节的途径，探索了一些有前景的信号通路，这些信号通路可以作为未来研究的起点。
