Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester M1 5GD, UK.
Int J Mol Sci. 2023 Jul 18;24(14):11582. doi: 10.3390/ijms241411582.
Pim Kinases; Pim-1, Pim-2, and Pim-3, are a family of constitutively active serine/threonine kinases, widely associated with cell survival, proliferation, and migration. Historically considered to be functionally redundant, independent roles for the individual isoforms have been described. Whilst most established for their role in cancer progression, there is increasing evidence for wider pathological roles of Pim kinases within the context of cardiovascular disease, including inflammation, thrombosis, and cardiac injury. The Pim kinase isoforms have widespread expression in cardiovascular tissues, including the heart, coronary artery, aorta, and blood, and have been demonstrated to be upregulated in several co-morbidities/risk factors for cardiovascular disease. Pim kinase inhibition may thus be a desirable therapeutic for a multi-targeted approach to treat cardiovascular disease and some of the associated risk factors. In this review, we discuss what is known about Pim kinase expression and activity in cells of the cardiovascular system, identify areas where the role of Pim kinase has yet to be fully explored and characterised and review the suitability of targeting Pim kinase for the prevention and treatment of cardiovascular events in high-risk individuals.
Pim 激酶;Pim-1、Pim-2 和 Pim-3 是一组组成型激活的丝氨酸/苏氨酸激酶,广泛参与细胞存活、增殖和迁移。历史上被认为具有功能冗余性,已描述了各个同工型的独立作用。虽然它们在癌症进展中的作用已得到广泛证实,但越来越多的证据表明 Pim 激酶在心血管疾病的背景下具有更广泛的病理作用,包括炎症、血栓形成和心脏损伤。Pim 激酶同工型在心血管组织中广泛表达,包括心脏、冠状动脉、主动脉和血液,并已在几种心血管疾病的合并症/危险因素中被证明上调。因此,抑制 Pim 激酶可能是一种理想的治疗方法,可用于针对心血管疾病及其相关危险因素的多靶点治疗。在这篇综述中,我们讨论了已知的 Pim 激酶在心血管系统细胞中的表达和活性,确定了 Pim 激酶作用尚未得到充分探索和描述的领域,并回顾了针对 Pim 激酶预防和治疗高危人群心血管事件的适宜性。