Elena V. Galitsyna

Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis

Mutations of mtDNA, due to their higher frequency of occurrence compared to nuclear DNA mutations, are the most promising biomarkers for assessing predisposition of the occurrence and development of atherogenesis. The aim of the present article was an analysis of correlation of several mitochondrial genome mutations with carotid atherosclerosis. Leukocytes from blood of study participants from Moscow polyclinics were used as research material. The sample size was 700 people. The sample members were diagnosed with “atherosclerosis” on the basis of ultrasonographic examination and biochemical and molecular cell tests. DNA was isolated from blood leukocyte samples of the study participants. PCR fragments of DNA, containing the region of 11 investigated mutations, were pyrosequenced. The heteroplasmy level of these mutations was detected. Statistical analysis of the obtained results was performed using the software package SPSS 22.0. According to the obtained results, an association of mutations m.652delG, m.3336C>T, m.12315G>A, m.14459G>A m.15059G>A with carotid atherosclerosis was found. These mutations can be biomarkers for assessing predisposition to this disease. Additionally, two single nucleotide substitutions (m.13513G>A and m.14846G>A), negatively correlating with atherosclerotic lesions, were detected. These mutations may be potential candidates for gene therapy of atherosclerosis and its risk factors.

Potential use of buccal epithelium for genetic diagnosis of atherosclerosis using mtDNA mutations

1Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow 121552, Russia. 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia. 3Department of Genetics, Southern Federal University, Rostov-on-Don 344006, Russia. 4Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow 121609, Russia. 5Federal Scientific Clinical Center for Resuscitation and Rehabilitation, Moscow 109240, Russia.

New markers of atherosclerosis: a threshold level of heteroplasmy in mtDNA mutations

1Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, 121552 Moscow, Russia. 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. 3Institute for Atherosclerosis Research, Skolkovo Innovative Centre, 121609 Moscow, Russia. 4Unit for the Study of Morphology and Arterial Function, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy.

Small dense and desialylated low density lipoprotein in diabetic patients

1Department of Cardiovascular Pathology, Russian Cardiology Research and Production Complex, 121552 Moscow, Russia. 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. 3Department of Genetics, Southern Federal University, 344090 Rostov-on-Don, Russia. 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia. 5Federal Scientific Clinical Center for Resuscitation and Rehabilitation, 109240 Moscow, Russia.

Mitochondrial diseases caused by mtDNA mutations: a mini-review

There are several types of mitochondrial cytopathies, which cause a set of disorders, arise as a result of mitochondria’s failure. Mitochondria’s functional disruption leads to development of physical, growing and cognitive disabilities and includes multiple organ pathologies, essentially disturbing the nervous and muscular systems. The origins of mitochondrial cytopathies are mutations in genes of nuclear DNA encoding mitochondrial proteins or in mitochondrial DNA. Nowadays, numerous mtDNA mutations significant to the appearance and progress of pathologies in humans are detected. In this mini-review, we accent on the mitochondrial cytopathies related to mutations of mtDNA. As well known, there are definite set of symptoms of mitochondrial cytopathies distinguishing or similar for different syndromes. The present article contains data about mutations linked with cytopathies that facilitate diagnosis of different syndromes by using genetic analysis methods. In addition, for every individual, more effective therapeutic approach could be developed after wide-range mutant background analysis of mitochondrial genome.

Cybrid Models of Pathological Cell Processes in Different Diseases

Modelling of pathological processes in cells is one of the most sought-after technologies of the 21st century. Using models of such processes may help to study the pathogenetic mechanisms of various diseases. The aim of the present study was to analyse the literature, dedicated to obtaining and investigating cybrid models. Besides, the possibility of modeling pathological processes in cells and treatment of different diseases using the models was evaluated. Methods of obtaining Rho0 cell cultures showed that, during their creation, mainly a standard technique, based on the use of mtDNA replication inhibitors (ethidium bromide), was applied. Cybrid lines were usually obtained by PEG fusion. Most frequently, platelets acted as donors of mitochondria. According to the analysis of the literature data, cybrid cell cultures can be modeled to study the dysfunction of the mitochondrial genome and molecular cellular pathological processes. Such models can be very promising for the development of therapeutic approaches to the treatment of various human diseases.

Response to: Comment on “Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis”

15a 3rd Cherepkovskaya Str, National Medical Research Center of Cardiology, Moscow 121552, Russia 8 Baltiyskaya Str, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology-MVA, Moscow 109472, Russia Department of Genetics, 105/42 B. Sadovaya Str, Southern Federal University, Rostov-on-Don 344006, Russia Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow 121609, Russia

Mitochondrial Genome Mutations Associated with Myocardial Infarction

Myocardial infarction is one of the clinical manifestations of coronary heart disease. In some cases, the cause of myocardial infarction may be atherosclerotic plaques which occurred in the human aorta. The association of mtDNA mutations with atherosclerotic lesions in human arteries was previously detected by our research group. In this study, we used samples of white blood cells collected from 225 patients with myocardial infarction and 239 control persons with no health complaints. DNA was isolated from the blood leukocyte samples. Then, PCR fragments of DNA were obtained. They contained the investigated regions of 11 mitochondrial genome mutations (m.5178C>A, m.3336T>C, m.652delG, m.12315G>A, m.14459G>A, m.652insG, m.14846G>A, m.13513G>A, m.1555A>G, m.15059G>A, m.3256C>T). According to the obtained results, three mutations of the human mitochondrial genome correlated with myocardial infarction. A positive correlation was observed for mutation m.5178C>A. At the same time, a highly significant negative correlation with myocardial infarction was observed for mutation m.14846G>A. One single-nucleotide substitution of m.12315G>A had a trend towards negative correlation. These mutations can potentially be useful for creating molecular/cellular models for studying the mechanisms of myocardial infarction and designing novel therapies. Moreover, these mutations can possibly be used for diagnostic purposes.