Cardiac Microtubules in Heart Failure:New Therapeutic Targets?
Microtubules are unbranched hollow tubular structures in the cytoskeleton composed of tubulin filaments.Microtubules are distributed in a network and are involved in maintaining cell morphology,polarity,motility and division and intracellular signal transduction.Heart failure is a major cardiovascular problem for which therapy is challenging.Cardiac microtubules have recently been found to be involved in the development of heart failure.Here,we review the structure and function of microtubules,their role in heart failure and related mechanisms to aid in the discovery of new targets for heart failure treatment.Increased microtubule density and stability are observed in heart failure cardiomyocytes,and the mechanism may be related to the increased concentration of posttranslationally modified tubulin,of which detyrosinated tubulin is the most dominant.Inhibition of detyrosinated tubulin expression significantly improves myocardial systolic or diastolic performance by increasing relaxation kinetics and reducing myocardial and cardiomyocyte stiffness.In conclusion,cardiac microtubules are involved in heart failure development and may therefore be new targets for heart failure treatment.
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