Review Article Open Access
Volume 2 | Issue 3 | DOI: https://doi.org/10.33696/Signaling.2.048

NH2-Terminal Cleavage of Cardiac Troponin I Signals Adaptive Response to Cardiac Stressors

  • 1Department of Physiology & Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, USA
  • 2Division of Cardiology, Center for Cardiovascular Research, University of Illinois at Chicago, USA
  • #These authors made equal contributions to this manuscript
+ Affiliations - Affiliations

Corresponding Author

R. John Solaro, solarorj@uic.edu

Received Date: July 26, 2021

Accepted Date: August 16, 2021


Cardiac sarcomeres express a variant of troponin I (cTnI) that contains a unique N-terminal extension of ~30 amino acids with regulatory phosphorylation sites. The extension is important in the control of myofilament response to Ca2+, which contributes to the neuro-humoral regulation of the dynamics of cardiac contraction and relaxation. Hearts of various species including humans express a stress-induced truncated variant of cardiac troponin I (cTnI-ND) missing the first ~30 amino acids and functionally mimicking the phosphorylated state of cTnI. Studies have demonstrated that upregulation of cTnI-ND potentially represents a homeostatic mechanism as well as an adaptive response in pathophysiology including ischemia/reperfusion injury, beta adrenergic maladaptive activation, and aging. We present evidence showing that cTnI-ND can modify the trigger for hypertrophic cardiomyopathy (HCM) by reducing the Ca2+ sensitivity of myofilaments from hearts with an E180G mutation in α-tropomyosin. Induction of this truncation may represent a therapeutic approach to modifying Ca2+-responses in hearts with hypercontractility or heat failure with preserved ejection fraction.


Sarcomeres, Ca2+-sensitivity, Hypertrophic cardiomyopathy, Heart failure, Tropomyosin

Author Information X