"This suggests a new strategy for treating hypertrophic heart disease through inhibition of CIB1 or its interaction with calcineurin.”
Molkentin also is a professor of pediatrics at the UC College of Medicine. Pre-existing cardiac hypertrophy from chronic health conditions like hypertension (high blood pressure) or a history of heart attacks is a major risk factor for heart failure.
After these conditions damage the heart, heart muscle cells called cardiomyocytes enlarge as the body tries to respond and compensate, increasing the organ’s size. The researchers first set out to identify previously unknown regulators of cardiomyocyte growth during hypertrophy. This was done through genetic analysis of neonatal rat heart cells cultured in the laboratory and programmed to become hypertrophic.
Genetic screens detected elevated levels of CIB1 – which helps mediate biochemical processes in the plasma membranes of various mouse and human tissues, especially the heart – and identified the protein as a prime candidate.
Additional analysis of hypertrophied mouse and human heart tissue also detected elevated levels of CIB1 in the sarcolemma, the thin plasma membrane surrounding heart muscle fiber that is important to receiving and serving as a conductor of stimuli. In experiments designed to monitor the levels, function and molecular interactions of CIB1 during heart injury in living organisms, the scientists conducted hypertension simulation tests on mice. Mice were generated that either lack the CIB1 gene or that over express CIB1 in the heart. Mice with over-expressed cardiac-specific CIB1 exhibited pronounced cardiac hypertrophy and dysfunction with hypertension stimulation, but mice lacking the CIB1 gene showed protection from hypertrophy and dysfunction.
Although the study points to CIB1 and its interaction with calcineurin as possible therapeutic targets, Molkentin cautioned that extensive additional research is needed before the data becomes clinically applicable to patients.