3′,5′-Cyclic guanosine monophosphate (cGMP) is one of the major second messengers critically involved in the regulation of cardiac electrophysiology, hypertrophy, and contractility. Recent molecular and cellular studies have significantly advanced our understanding of the cGMP signalling cascade, its local microdomain-specific regulation and its role in protecting the heart from pathological stress. Here, we summarise recent findings on cardiac cGMP microdomain regulation and discuss their potential clinical significance.

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