Introduction.
Cardiovascular diseases are one of the leading causes of death and disability in the population. Laboratory diagnostics of cardiovascular diseases is an important direction, since it is one of the key methods of diagnosis verification [1, 2, 3].
In recent years, many clinical studies have been conducted on recently discovered biomarkers of cardiovascular diseases [4, 5], among which catestatin, highly sensitive cardiac troponins, and proprotein-convertase subtilisin/Kexin type 9 are particularly noteworthy [1-10].
The diagnostic value of these biomarkers of cardiovascular diseases is discussed in more detail below.
Catestatin
Catestatin is a hydrophobic neuroendocrine peptide of 21 amino acid residues, which is formed as a result of proteolytic cleavage of chromogranin A by endogenous proteases [11]. Catestatin is stored in secretory granules of chromaffin cells of the adrenal medulla and adrenergic neurons and inhibits the secretion of catecholamines in mammals, for which it received its name [12]. Catestatin was first detected in 1997 in chromaffin cells of the adrenal medulla. Subsequently, it was also found in secretory granules of the diffuse neuroendocrine system, cardiomyocytes, neutrophils, and keratinocytes [7]. The catestatin molecule performs several important functions in the human body: antihypertensive by inhibiting the release of catecholamines and vasodilation, hypoglycemic (insulin-like) action by increasing glucose uptake by cardiomyocytes, antiatherosclerotic by reducing the inflammatory response, protection from ischemia/reperfusion in myocardial infarction, antiapoptotic action [7, 11]. A number of researchers have developed methods for determining (enzyme immunoassay and radioimmune assays) catestatin in blood plasma and attempted to use it as a diagnostic marker of some cardiovascular diseases. The level of catestatin decreases in the early stages of hypertension, even in normotensive people with a high risk of developing this disease, which allows us to consider lowered catestatin levels as predictors of the development of hypertension. Increased levels of catestatin in myocardial infarction and in the post-infarction period have a protective effect, reducing the harmful effects of catecholamines on the myocardium. Patients with St-segment elevation myocardial infarction (STEMI) have higher levels of catestatin than patients with unstable angina [12].
Highly sensitive cardiac troponins
Cardiac troponins are released when the myocardium is damaged by several mechanisms [13-15]. With reversible damage, the integrity of the cardiomyocyte membrane is violated, and there is a partial breakdown of the cytosolic troponin pool into smaller fragments and their exit into the bloodstream. With irreversible damage, intracellular acidosis increases and proteolytic enzymes are activated, which destroy the contractile apparatus of cardiomyocytes [16, 17]. The introduction of highly sensitive test systems into clinical practice allowed detecting cardiac troponins in almost all healthy people in low concentrations (below 99-percentile) [17, 18].
Troponins are also found in other biological fluids: serous cavity fluids, liquor, urine, and oral fluid [19]. The study of troponins in pericardial fluid is used in forensic medical examination, and the determination in urine and oral fluid is of significant interest for non-invasive diagnostics and monitoring of cardiovascular diseases [19, 20, 21, 22].
An increase in cardiac troponins (cTn) in biological fluids indicates reversible or irreversible damage to cardiomyocytes, but does not explain the etiology and pathogenesis of this damage [23, 24].
Highly sensitive cardiac troponins are valuable diagnostic biomarkers of cardiovascular diseases and are often used in modern research [13-25].
Proprotein convertase subtilisin Kexin type 9
Currently, it is generally recognized that increased levels of total cholesterol and low-density lipoproteins significantly increase the risk of cardiovascular disease [25-30].
In 2003, the Canadian researcher Seidah N. G. identified the enzyme – proprotein convertase subtilisin Kexin type 9 [25]. The protein proprotein convertase subtilisin Kexin type 9 is a serine protease of the subtilase family (protein convertases), mainly expressed in the liver and to a much lesser extent in the brain, intestines, and kidneys [26]. Proprotein convertase subtilisin Kexin type 9 is synthesized on the ribosomes of the endoplasmic reticulum (ER) as an inactive precursor (zymogen) – Pro-proprotein convertase subtilisin kexin type 9 with a molecular weight of 72 kDa, which after posttranslational modifications in ER tanks and Golgi apparatus turns into a Mature enzyme proprotein convertase subtilisin kexin type 9 [27]. The main function of proprotein convertase subtilisin kexin type 9 is to regulate the number of low-density lipoprotein receptors on the surface of hepatocytes [28].
According to current data, proprotein convertase subtilisin kexin type 9 is considered as a promising biomarker for early diagnosis of atherosclerosis and cardiovascular diseases [29, 30].
References
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