Mitochondria and the heart
"Myocardial infarction mutations" found in mitochondrial DNA
Researchers from the Institute of General Pathology and Pathophysiology, the National Medical Research Center of Cardiology, the Southern Federal University and the Skolkovo Innovation Center have studied how the composition of mitochondrial DNA affects the likelihood of developing a number of cardiovascular diseases. They found 11 variants of mutations associated with an increased risk of atherosclerosis, and three variants associated with an increased or, conversely, a reduced probability of myocardial infarction. The authors hope that the data they have obtained will facilitate the early diagnosis of a heart attack or help create new experimental models of this disease. The scientific article was published in the journal Disease Markers (Sazonova et al., Mitochondrial Genome Mutations Associated with Myocardial Infarction). The study was supported by a grant from the Russian National Science Foundation.
The study involved 225 patients with myocardial infarction and 239 people without cardiovascular diseases. All of them were patients of the MSU University Clinic or the Cardiology Research Complex of the Ministry of Health of the Russian Federation. Although the composition of the subjects was chosen by chance, the first group was dominated by men, the second by women. In addition, the average age of study participants without cardiovascular diseases was 13 years less.
DNA samples of mitochondria (these organoids have their own ring DNA molecule, which differs from the nucleus chromosomes by a set of genes) were extracted from the leukocytes of the subjects' blood. Further, small fragments of this DNA were "multiplied" using a polymerase chain reaction and the sequence of nucleotides in them was determined by pyrosequencing.
First of all, scientists were interested in genes whose mutations were linked to the formation of atherosclerotic plaques, they had already shown in previous studies. These genes were read using pyrosequencing. They previously found 11 variants of substitutions, inserts and drops of individual nucleotides. The occurrence of such changes in the composition of genes (they are called single nucleotide polymorphisms) of mitochondria was compared in patients with myocardial infarction and atherosclerosis and in members of the control group.
Of all the single-nucleotide polymorphisms studied, two were associated with a reduced risk of myocardial infarction and one with an increased risk (they are two or more times more common in the control group and the group of patients with heart attack, respectively). It is important to note that single-nucleotide polymorphisms are usually called variants of the structure of genes that occur with a frequency of more than one percent and are not always associated with diseases. Mutations are a rarer phenomenon – they appear in less than one percent of cases. However, since scientists in this case were looking for polymorphisms associated with pathologies, in their article they call them mutations, despite the frequency of their occurrence.
Interestingly, the DNA region in which the genetic risk factor for heart attack was found encodes one of the proteins necessary for mitochondria to produce energy. Apparently, a mutation in it reduces the energy efficiency of the fibers of the heart muscle, which is why they are more sensitive to nutritional disorders due to ischemic disease than normal. And single-nucleotide polymorphisms, presumably protecting the heart from a heart attack, in previous works of other authors were associated with a mass of pathological conditions: muscle weakness, the presence of the protein myoglobin in urine, etc. So far there is no explanation for this fact.
Myocardial infarction is one of the clinical manifestations of coronary heart disease. With it, the nutrition of the fibers in the heart muscle is disrupted, since the lumen of the vessels carrying blood to this organ narrows due to their filling with atherosclerotic plaques. Due to lack of nutrition, part of the muscle fibers of the heart dies and is partially replaced by connective tissue cells. In fact, a scar forms on the heart – an area that is not capable of contraction. As a result, it disrupts the work of the entire organ. However, vascular atherosclerosis does not always lead to the development of a heart attack, and according to the condition of the patient with atherosclerosis, it is impossible to determine unequivocally whether he will have a heart attack or not. At the moment, there are no reliable methods of early diagnosis of myocardial infarction and genetic predisposition to it. The authors of the study express the hope that the data they have obtained will help in the development of such methods.
Previously, only lifestyle-related risk factors for myocardial infarction were known: overweight, sedentary lifestyle and smoking. The described work shows that in addition to external factors, there are also internal ones – genetic, moreover, related not to the DNA of the nucleus, but to the genome of mitochondria. The next interesting question is how these two types of risk factors affect each other.
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