Majaj Marina, Weckbach Ludwig T
Walter Brendel Centre for Experimental Medicine, Biomedical Centre, Institute for Cardiovascular Physiology und Pathophysiology, Ludwig-Maximilians-University Munich, Munich, Germany.
Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Front Cardiovasc Med. 2022 Sep 20;9:1003104. doi: 10.3389/fcvm.2022.1003104. eCollection 2022.
Midkine (MK) is a 13-kDa heparin-binding cytokine and growth factor with anti-apoptotic, pro-angiogenic, pro-inflammatory and anti-infective functions, that enable it to partake in a series of physiological and pathophysiological processes. In the past, research revolving around MK has concentrated on its roles in reproduction and development, tissue protection and repair as well as inflammatory and malignant processes. In the recent few years, MK's implication in a wide scope of cardiovascular diseases has been rigorously investigated. Nonetheless, there is still no broadly accepted consensus on whether MK exerts generally detrimental or favorable effects in cardiovascular diseases. The truth probably resides somewhere in-between and depends on the underlying physiological or pathophysiological condition. It is therefore crucial to thoroughly examine and appraise MK's participation in cardiovascular diseases. In this review, we introduce the MK gene and protein, its multiple receptors and signaling pathways along with its expression in the vascular system and its most substantial functions in cardiovascular biology. Further, we recapitulate the current evidence of MK's expression in cardiovascular diseases, addressing the various sources and modes of MK expression. Moreover, we summarize the most significant implications of MK in cardiovascular diseases with particular emphasis on MK's advantageous and injurious functions, highlighting its ample diagnostic and therapeutic potential. Also, we focus on conflicting roles of MK in a number of cardiovascular diseases and try to provide some clarity and guidance to MK's multifaceted roles. In summary, we aim to pave the way for MK-based diagnostics and therapies that could present promising tools in the diagnosis and treatment of cardiovascular diseases.
中期因子（MK）是一种13千道尔顿的肝素结合细胞因子和生长因子，具有抗凋亡、促血管生成、促炎和抗感染功能，使其能够参与一系列生理和病理生理过程。过去，围绕MK的研究主要集中在其在生殖与发育、组织保护与修复以及炎症和恶性过程中的作用。近年来，MK在广泛的心血管疾病中的作用已得到深入研究。然而，对于MK在心血管疾病中总体上是产生有害还是有益影响，仍没有广泛接受的共识。事实可能介于两者之间，并且取决于潜在的生理或病理生理状况。因此，彻底研究和评估MK在心血管疾病中的参与情况至关重要。在本综述中，我们介绍了MK基因和蛋白、其多种受体和信号通路，以及它在血管系统中的表达及其在心血管生物学中的最重要功能。此外，我们概述了目前关于MK在心血管疾病中表达的证据，阐述了MK表达的各种来源和方式。而且，我们总结了MK在心血管疾病中的最重要影响，特别强调了MK的有利和有害功能，突出了其丰富的诊断和治疗潜力。同时，我们关注MK在一些心血管疾病中的矛盾作用，并试图为MK的多方面作用提供一些清晰的解释和指导。总之，我们旨在为基于MK的诊断和治疗方法铺平道路，这些方法可能为心血管疾病的诊断和治疗提供有前景的工具。
