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Page 2 of 7 Sazonova et al. Vessel Plus 2019;3:8 I http://dx.doi.org/10.20517/2574-1209.2019.01

Conclusion: MtDNA mutations m.14459G>A and m.5178C>A can be used for evaluation the predisposition of individuals
to atherosclerotic lesions. At the same time, mitochondrial genome mutation m.15059G>A may be used for gene therapy
of atherosclerosis.

Keywords: Cardiac angina, gene, mutation, heteroplasmy level, mitochondrial genome, molecular cellular models

INTRODUCTION
Cardiac angina is a disease in which discomfort or retrosternal pain may occur. Discomfort is felt by
patients as pressure or retrosternal burning. Pain often occurs during physical exertion, excessive food
[1-5]
ingestion, stress, being in cold air or with a sharp increase in blood pressure . Cardiac angina is supposed
to be caused by narrowing of the arterial lumen up to 50%-75%. As a result, there is a discrepancy between
the blood flow to the heart and its need for blood. In this case, acute insufficiency of blood supply to the
[2-6]
heart happens. The redox processes in the heart muscle become disrupted . An excessive accumulation
of insufficiently oxidized metabolic products (lactic, pyruvic, carbonic and phosphoric acids) and other
metabolites occurs. Cardiac angina occurs most often in men over 40, and in women over 50 years. The
prevalence of cardiac angina increases with age. For example, in patients who were older than 65 years, the
frequency of occurrence of cardiac angina reached 10%-20%. One of the main risk factors for cardiac angina
is a atherosclerosis of coronary arteries [2-6] . Other risk factors for cardiac angina include hypertension,
diabetes mellitus, obesity, smoking; stress, hypodynamia, infectious diseases, allergic lesions and genetic
mutations [7-12] .

Molecular genetic markers for cardiac angina could help identification of predisposition to the disease much
earlier than clinical methods for examining patients. At the present time, such studies are mainly devoted to
polymorphisms of the genes in nuclear genome.

Our research group found a number of mitochondrial genome mutations associated with cardiac angina.
It should be noted that in the study we investigated those mitochondrial mutations for which, in our
preliminary studies, we detected an association with atherosclerosis [13-17] . Since atherosclerosis is a risk factor
for cardiac angina, we decided to investigate whether these mutations are linked with cardiac angina.

It should be noted that during the investigation of the mitochondrial genome mutations, the level of
heteroplasmy is determined. The ratio of the number of mutant mitochondrial DNA (mtDNA) copies in a
sample to the total number of mtDNA copies is estimated [13-17] . This is the difference between quantitative
analysis of mutations in the mitochondrial genome and the analysis of nuclear mutations. In the quantitative
analysis of nuclear genome mutations, the number of homozygotes in which both alleles are either mutant or
normal. The number of heterozygotes is detected too. Afterwards the mutation frequency in the investigated
sample is estimated [18,19] .

The level of heteroplasmy in mitochondrial genome mutations was measured using a quantitative method
developed in our laboratory [14,17,20] . This method is based on the pyrosequencing technology [21,22] . Short DNA
fragments (6-10 bp), containing the area of mutation were investigated. Such a small length of the studied
DNA fragments significantly reduces the number of errors during sequencing.

METHODS
We used samples of white blood cells collected from 192 patients with cardiac angina and 201 conventionally
healthy study participants. These individuals were examined in Moscow State University clinic. In order to