Remodeling of rat cardiomyocytes after neonatal cryptosporidiosis. I. Change of ratio of isoforms of myosin heavy chains

Abstract

Diseases of the human cardiovascular system are the main cause of death in developed countries. Therefore, searching for new risk factors thereof is of particular interest. Upon comparing epidemiological data with data of transcriptome of cardiomyocytes and comparative physiology of vertebrate ontogenesis, we have come to the conclusion that one such factor may be gastroenteritis. This disease includes at once several stimuli able to cause functional and metabolic alterations in the heart: tachycardia, hormonal and ionic misbalance, and outflow of resources from the cardiovascular system. Using the model of rat neonatal gastroenteritis caused by the widespread human and animal enteropathogen Cryptosporidium parvum (Apicomplexa, Sporozoa), we studied the change of expression of α- and β-myosin heavy chains after the developed cryptosporidiosis. Online data obtained by methods of immunocytochemistry, quantitative morphometry, and polymerase chain reaction not only have confirmed our suggestion, but also have shown that moderate 4-day-long cryptosporidiosis is sufficient for producing a significant (1.7- to 4.5-fold) shift in the ratio of myosin isoforms toward the β-isoform beta at the level of mRNA and at the level of protein (2.5–6 times). The reciprocity of the changes, as well as their clear similarity at the level of mRNA and of protein, indicates that the cryptosporidial gastroenteritis involves all the main chains of a complex network of regulation of expression of the myosin heavy chains. A shift of the ratio of myosin isoforms toward the β-isoform that has an ATPase activity several times lower than the α-isoform is the commonly accepted indicator of human heart failure; therefore, the cryptosporidial gastroenteritis can be considered a novel risk factor for decrease of the heart’s contractile ability. Our data may be of interest for clinical and preventive medicine.