Regulation of the ratio of neurotransmitters and matrix metalloproteinases is a new strategy for secondary prevention of patients with multifocal atherosclerosis

Abstract

Multifocal atherosclerosis (MAS) remains one of the key problems of modern medicine, despite advances in primary and secondary prevention of myocardial infarction (MI) and ischemic stroke (IS). MAS worsens the prognosis and increases the risk of atherosclerotic plaque (AP) destabilization, especially under the influence of matrix metalloproteinases (MMPs). Activation of the sympatho-adrenal and serotonergic systems with the release of dopamine and serotonin also plays a significant role in the pathogenesis of this process, influencing the regulation of vascular tone and blood flow in various organs.

The aim of this study was to study the possibilities of normalizing the balance of serotonin and dopamine in patients with MAS to stabilize the atherosclerotic process and improve the regional hemodynamics of the heart, brain, and lower extremities.

Materials and methods. The study involved 54 men aged 60 to 90 years, including the first group (n = 26) patients with MAS with intermittent claudication, atherosclerotic encephalopathy and post-infarction cardiosclerosis; the second group (n = 28) patients with MAS who had IS, with concomitant atherosclerosis of the coronary and femoral arteries, and the control group – 18 people of comparable age. Examination: ankle-brachial index, Holter ECG monitoring, walking distance, dopplerography with determination of volumetric blood flow indicators. Blood levels of serotonin, dopamine, MMP-2 and MMP-9 were determined. Cognitive function was assessed using the Montreal scale. In addition, patients of both groups were prescribed cilostazol (50 mg twice a day), GABA – aminalon (250 mg twice a day) and atenolol (25 mg once a day).

Results. The results of the study showed significant disorders of hemodynamics and neurotransmitter balance in patients with MAS. We found a significant (p < 0.001) excess of serotonin in the blood serum, an increase of dopamine (p < 0.01) by 60–70 % more than in control group persons. The morning peak of a 5–7-fold increase in plasma serotonin levels is noteworthy. Levels of MMP-2 and MMP-9 were almost twice as high (p < 0.01) in patients who experienced IS or MI compared with the control group. After the addition of cilostazol, aminalon and atenolol to the basic therapy, we found a significant decrease in the ultra-high levels of serotonin in blood plasma (p < 0.001) and serum (p < 0.05). The levels of MMP-2 (p < 0.01) decreased, volumetric blood flow indicators improved in all three studied arteries (p < 0.05), the painless walking distance and maximum walking distance increased, and cognitive functions improved significantly (p < 0.05).

Conclusions. The proposed new strategy for secondary prevention of cardiovascular events in patients with MAS with a history of ischemic stroke or myocardial infarction is based on the correction of the imbalance of neurotransmitters serotonin and dopamine by adding to the basic therapy, according to the latest guidelines 2024, a complex of drugs – cilostazol, aminalon and atenolol.