A study determines whether CKIP-1 was also involved in the regulation of cardiac remodeling induced by microgravity. The human cardiovascular system has adapted to Earth's gravity of 1G. The microgravity during space flight can induce cardiac remodeling and decline of cardiac function. At present, the mechanism of cardiac remodeling induced by microgravity remains to be disclosed.

Casein kinase-2 interacting protein-1 (CKIP-1) is an important inhibitor of pressure-overload-induced cardiac remodeling by decreasing the phosphorylation level of HDAC4. However, the role of CKIP-1 in the cardiac remodeling induced by microgravity is unknown. They first detected the expression of CKIP-1 in the heart from mice and monkey after simulated microgravity using Q-PCR and western blotting.

Then, myocardial specific CKIP-1 transgenic (TG) and wild-type mice were hindlimb-suspended (HU) to simulate microgravity effect. The human cardiovascular system has adapted to Earth's gravity of 1G, and cardiac muscle is well regulated in response to changes in loading conditions. When exposed to microgravity during space flight, there are various changes in cardiac mass and cardiac systolic volume.

Microgravity can induce the chronic reduction in metabolic demand and oxygen uptake which reduces the demand for cardiac output, resulting in cardiac atrophy and the decline of cardiac function. Our previous study demonstrated that pathological cardiac remodeling signals, such as HDAC4 and ERK1/2, were activated, and physiological cardiac remodeling signals, such as AMPK, were inactivated in the heart of mice after hindlimb unloading, which might lead to cardiac remodeling and decline of heart function.

Beyond that, we know little about the mechanisms regulating cardiac atrophy induced by microgravity. Also, the prevention of cardiac remodeling induced by simulated microgravity via inhibiting the changes of these signals activity needs to be elucidated.

Myocardial CKIP-1 Overexpression Protects from Simulated Microgravity Induced-Cardiac Atrophy

In this study, we found CKIP-1 mRNA and protein levels in hearts of mice and rhesus monkeys after simulated microgravity were significantly decreased. The results showed myocardial CKIP-1 overexpression protected from the decline of cardiac function, the atrophy of cardiomyocyte and changes in phosphorylation levels of signal factors induced by simulated microgravity. They demonstrated myocardial CKIP-1 overexpression protected from cardiac remodeling induced by simulated microgravity.

Here, they identified CKIP-1 as a novel regulator of simulated microgravity-induced cardiac remodeling. CKIP-1 mRNA and protein levels were significantly downregulated in the hearts of mice after 28 days of hindlimb unloading and rhesus monkeys after 42 days of head-down bed rest. Myocardial CKIP-1 overexpression protected from simulated microgravity induced-decline of cardiac function and loss of left ventricular mass.

Histological analysis demonstrated CKIP-1 TG inhibited the decrease in the size of individual cardiomyocytes of mice after hindlimb unloading. Moreover, the pathological cardiac remodeling signals, such as ERK1/2 and HDAC4, were activated, and physiological cardiac remodeling signals, such as AMPK, were inactivated in the heart of WT mice after hindlimb unloading, however, CKIP-1 TG mice displayed a different trend. 

Myocardial CKIP-1 overexpression inhibited the changes of phosphorylation levels of signal factors in mice heart induced by simulated microgravity. So, CKIP-1 manifests important functional significance during cardiac stress response resulting from space flight.