Doença cardiovascular continua a ser o maior assassino dos americanos adultos e um problema crescente em todo o mundo. Infelizmente, os diabéticos são significativamente mais propensos a sofrer de problemas cardiovasculares, em comparação aos pacientes sem diabetes. Chocante, mais de 50% de mortes entre pacientes diabéticos resultado de doenças cardiovasculares e um dos efeitos mais frequentes que a diabetes tem sobre o coração é causar cardiomiopatia ou um enfraquecimento do músculo do coração. Às vezes, a cardiomiopatia pode desenvolver mesmo na ausência de doença arterial coronariana, hipertensão ou doença cardíaca congênita. Nesses casos, pacientes com diabetes que desenvolvem cardiomiopatia são descritos como portadores de cardiomiopatia diabética; Esta condição apresenta-se muitas vezes com um alargada do ventrículo esquerdo e fibrose, mas nenhuma evidência de danos de artéria coronária.
An interesting detail about diabetic heart disease that many patients may not know is that several research studies have shown that intracellular pathways can activate 'transcription factors' and influence the disease process. These changes in transcription then go on to trigger gene expression, which in turn causes structural changes in the heart. The process is known as cardiac remodeling. Surprisingly then, diabetic cardiomyopathy is accompanied by altered gene expression within the body. Scientists are learning more and more about how the process works in an attempt to better diagnose and treat conditions like diabetic cardiomyopathy and other heart disorders. Epigenetics and microRNAs are recent parts of the puzzle; scientists continue to work on understanding their relationship and their role in gene expression.
Epigenetics, for their part, are generally described as heritable changes in gene expression that cannot be explained by changes to the sequence of the DNA. That is, they don't involve a change in the nucleotide sequence but rather changes to other processes like DNA methylation or histone modification. These changes cause the individual's genes to behave differently. Normally, epigenetic changes are preserved when a cell divides, so they tend to only occur within the duration of the organism's lifetime. If the process occurs during fertilization of an egg, then it is possible for some epigenetic changes to be passed to the next generation. Scientists know that some epigenetic changes are involved with diseases like diabetic cardiomyopathy, but more work still needs to be done in this area.
MicroRNAs (also known as miRNAs) help regulate gene expression. They are single-strand noncoding RNAs and bind to one protein to then generate mature miRNA. The mature miRNA then represses either fully or partially the expression of complementary target mRNAs. MiRNAs regulate gene expression by either promoting degradation or repressing translation of target mRNAs. This area of research does remain somewhat controversial - studies have shown that several forms of miRNA-mediated gene modulation exist, and furthermore that these are linked to several different types of cardiovascular disease. One theory is that epigenetics and miRNA influence each other. It may be the case that epigenetic changes cause miRNA to change in unexpected ways, or that alterations in miRNA influence how genes are expressed.
Diabetes also causes inflammation in the body as a response to high glucose in the blood. This inflammation can be another contributor to heart disease. While the relationship between inflammation and heart disease is intuitively appealing, the exact mechanisms are not fully understood. Some theories hold that high glucose levels increase the expression of inflammatory cytokines via decreased histone, but as yet there are no definitive conclusions about how the inflammatory process works. Another possibility is that methylation of nuclear DNA is involved in the cardiovascular disease process. Altered DNA methylation has been linked to impaired gene expression in recent studies on diabetic heart failure patients; three genes in particular were identified with DNA methylation pattern and a different expression between healthy subjects and those with cardiomyopathy.
Unfortunately for diabetics, their unique form of heart disease remains poorly understood in comparison with more common varieties of the disease. However, the mounting evidence that epigenetics and miRNA play a role in the process is useful because it allows researchers to direct their attention and time to finding solutions for the condition. Future treatments may even include therapies targeted at epigenetic changes.