Age-Dependent Protein Expression of Serine/Threonine Phosphatases and Their Inhibitors in the Human Cardiac Atrium

Abstract

Heart failure and aging of the heart show many similarities regarding hemodynamic and biochemical parameters. There is evidence that heart failure in experimental animals and humans is accompanied and possibly exacerbated by increased activity of protein phosphatase (PP) 1 and/or 2A. Here, we wanted to study the age-dependent protein expression of major members of the protein phosphatase family in human hearts. Right atrial samples were obtained during bypass surgery. Patients (n=60) were suffering from chronic coronary artery disease (CCS 2-3; New York Heart Association (NYHA) stage 1–3). Age ranged from 48 to 84 years (median 69). All patients included in the study were given β-adrenoceptor blockers. Other medications included angiotensin-converting enzyme (ACE) or angiotensin-receptor-1 (AT1) inhibitors, statins, nitrates, and acetylsalicylic acid (ASS). 100 µg of right atrial homogenates was used for western blotting. Antibodies against catalytic subunits (and their major regulatory proteins) of all presently known cardiac serine/threonine phosphatases were used for antigen detection. In detail, we studied the expression of the catalytic subunit of PP1 (PP1c); I1PP1 and I2PP1, proteins that can inhibit the activity of PP1c; the catalytic subunit of PP2A (PP2Ac); regulatory A-subunit of PP2A (PP2AA); regulatory B56α-subunit of PP2A (PP2AB); I1PP2A and I2PP2A, inhibitory subunits of PP2A; catalytic and regulatory subunits of calcineurin: PP2BA and PP2BB; PP2C; PP5; and PP6. All data were obtained within the linear range of the assay. There was a significant decline in PP2Ac and I2PP2A expression in older patients, whereas all other parameters remained unchanged with age. It remains to be elucidated whether the decrease in the protein expression of I2PP2A might elevate cardiac PP2A activity in a detrimental way or is overcome by a reduced protein expression and thus a reduced activity of PP2Ac.