Midkine's Role in Cardiac Pathology.

Kathleen Woulfe,Carmen Sucharov

doi:10.3390/jcdd4030013

Kathleen Woulfe, Carmen Sucharov

Open Access

https://doi.org/10.3390/jcdd4030013

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Abstract

Midkine (MDK) is a heparin-binding growth factor that is normally expressed in mid-gestational development mediating mesenchymal and epithelial interactions. As organisms age, expression of MDK diminishes; however, in adults, MDK expression is associated with acute and chronic pathologic conditions such as myocardial infarction and heart failure (HF). The role of MDK is not clear in cardiovascular disease and currently there is no consensus if it plays a beneficial or detrimental role in HF. The lack of clarity in the literature is exacerbated by differing roles that circulating and myocardial MDK play in signaling pathways in cardiomyocytes (some of which have yet to be elucidated). Of particular interest, serum MDK is elevated in adults with chronic heart failure and higher circulating MDK is associated with worse cardiac function. In addition, pediatric HF patients have higher levels of myocardial MDK. This review focuses on what is known about the effect of exogenous versus myocardial MDK in various cardiac disease models in an effort to better clarify the role of midkine in HF.

Highlights

Midkine (MDK) is a heparin-binding protein which plays a role in development as well as in many pathologic conditions [1,2,3,4,5,6,7,8,9,10]
In contrast to the ischemic injury models of cardiac pathology, this study suggests that elevated MDK is detrimental
This study demonstrates the importance of determining the role of MDK in ALL mechanisms of cardiac pathology before developing therapeutics

Summary

Introduction

Midkine (MDK) is a heparin-binding protein which plays a role in development as well as in many pathologic conditions [1,2,3,4,5,6,7,8,9,10]. MDK is involved in many different processes including growth and differentiation, repair, migration, and inflammation (reviewed in [8,9,11,12,13]) Since it is a secreted factor, MDK mediates these processes through extracellular interactions with a wide range of receptors. Its function is not known, it is missing a heparin-binding domain, but encodes the N-terminal signal peptide and is found in normal mouse embryos, suggestive of a unique role in organogenesis. This example highlights the importance of further investigation of MDK function and regulation. Develofupnmcteionntsa, allnyd, MMDKDhKas bmeeendfioautnedstoinretgeurlaactetieoxnprsessbioentwofePeTnN [m23e].sFeunrtchheyr,mPTeN aexnpdresesiponitchaenlial cells specificallycaofmfepcetnisnagteoforrglaonss mof oMrDpKhoexgpernesessioisn [in24d,e2v5e]lo. pInmeandt,uplatrst,icMulaDrlKy iinstheexpheraersts[2e3d]. in a limited number of tissues including kidney, intestines, epidermis, bronchial epithelium and macrophages [10]

MDK in Normal and Pathophysiology

Integrins

Intracellular MDK

Myocardial Infarction

Thoracic Aortic Constriction

Continuous Pacing

Indirect Cardiac Pathology

Consideration for Pediatric HF

Findings

Conclusions