Abstract
Investigation of myocardial tissue concentration of ATP, glucose transporters 1 and 4, pyruvate dehydrogenase, hexokinase 2, insulin receptor and adropin proteins, determining metabolic changes and possible insulin resistance in feline myocardium with hypertrophic phenotype. This is the pilot study for metabolic markers determination. Eighteen cats were studied, divided into 3 groups: Without cardiac disease (n = 5), cats with hypertrophic cardiomyopathy (n = 8), cats with chronic kidney disease and secondary myocardial hypertrophy (n = 5). Animals in the study were diagnosed for the primary disease by standard methods and algorithms. Cats were euthanized due to the end-stage chronic kidney disease, refractory heart failure or by owners’ will. The myocardium samples were obtained immediately after death. Samples for the metabolic study were taken from the apical part of the left ventricular free wall and fixed in liquid nitrogen at once and were stored in -80°C refrigerator. Studied proteins concentrations were analyzed in a specialized research laboratory, using ELISA kits, provided by Cloud-Clone Corp. (USA), included: Total ATP, pyruvate dehydrogenase, hexokinase II, Adropin, insulin receptor, GLUT1 and GLUT4. In the group with HCM, we discovered that levels of ATP, pyruvate dehydrogenase and adropin were severely suppressed in comparison to healthy cats, while GLUT1 and GLUT4 did not change. The concentration of hexokinase 2 and insulin receptor proteins significantly increased. In the group of secondary myocardial hypertrophy, suppression of most studied proteins was admitted, except insulin receptor. In conclusion, we discovered metabolic remodeling and development of insulin resistance in observed diseases with hypertrophy phenotype. We observed depression of pivotal enzymes proteins, limiting energy restoration potency for cardio myocytes.
Highlights
Heart failure syndrome is an aspect of primary or secondary heart disease and it is associated with decompensation, formation and activation of pathological interactions between components of neurohumoral regulation systems
Echocardiography showed mild left ventricular walls hypertrophy, associated with systemic hypertension. This manifestation is a part of Target-Organs Damage (TOD: Vessels, kidneys, heart, eyes, central nervous system) of systemic hypertension, which associated with Chronic Kidney Disease (CKD) (Leclerc et al, 2017; Vickery et al, 2005)
The obtained data from apparently healthy cats shows that myocardium has low insulin-depended source of glucose transporter and, possibly, normal CMC has alternative paths for carbohydrates
Summary
Heart failure syndrome is an aspect of primary or secondary heart disease and it is associated with decompensation, formation and activation of pathological interactions between components of neurohumoral regulation systems. Systolic dysfunction is associated with sympathetic nervous system activation, leading to heart rate acceleration This catecholamine-induced action provokes increased oxygen demand in the myocardium, increased Free Fatty Acids (FFA) consumption as an energy resource, ADP accumulation and negative inotropic effect. These conditions are well observed in chronic sympathetic hyperactivity in heart failure (Fukushima and Lopaschuk, 2016; Liu et al, 2001; Neubauer, 2007; Opie et al, 1979; Stanley et al, 1997a-b). During the utilization of these substrates, a proton generated, forming electrical potential between mitochondrial membranes and by the respiratory chain, ADP to ATP is phosphorylated (Ingwall, 2002; 2009; Taegtmeyer et al, 2016; Ventura‐Clapier et al, 2004)
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