Cardiomyocyte expression and cell-specific processing of procholecystokinin

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Molecular Biology

Background:

• Heart muscle cells produce peptide hormones like natriuretic peptides.
• The cholecystokinin (CCK) gene is expressed in developing hearts, but its protein-level expression in adult hearts was unaddressed.
• Previous studies suggested cardiac peptide expression beyond natriuretic peptides using transcriptional measures only.

Purpose of the Study:

• To investigate the expression and processing of the cholecystokinin (CCK) gene at the protein level in adult mammalian hearts.
• To determine if cardiac CCK has pathophysiological relevance and could serve as a marker for heart failure.

Main Methods:

• Quantitative PCR to assess gene expression.
• Sequence-specific pro-CCK assays.
• Peptide purification and mass spectrometry to identify and characterize cardiac CCK.
• In vitro and in vivo stimulation with isoprenaline.
• Measurement of plasma CCK levels in heart failure patients.

Main Results:

• The mammalian heart expresses pro-CCK protein at levels comparable to natriuretic prohormones.
• Cardiac CCK is processed into a unique, triple-sulfated, and N-terminally truncated peptide, distinct from intestinal and cerebral CCK.
• Isoprenaline rapidly stimulates cardiac CCK gene expression.
• Elevated plasma CCK levels were detected in heart failure patients.

Conclusions:

• The adult mammalian heart expresses and processes cholecystokinin (CCK) into a unique peptide product.
• Cardiac-specific truncated CCK shows potential as a novel biomarker for heart failure.
• Further research into the role of cardiac CCK in heart failure pathophysiology is warranted.