Type 1 Diabetes Impairs Cardiomyocyte Contractility in the Left and Right Ventricular Free Walls but Preserves It in the Interventricular Septum

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1719
• Main Authors: Khokhlova, Anastasia, Myachina, Tatiana, Volzhaninov, Denis, Butova, Xenia, Kochurova, Anastasia, Berg, Valentina, Gette, Irina, Moroz, Gleb, Klinova, Svetlana, Minigalieva, Ilzira, Solovyova, Olga, Danilova, Irina, Sokolova, Ksenia, Kopylova, Galina, Shchepkin, Daniil
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.02.2022; MDPI
• Subjects: Actin; actin-myosin interaction; Alloxan; Animals; Antibodies; Blood pressure; Calcium - metabolism; Calcium ions; calcium transients; Cardiomyocytes; Cardiomyopathy; Cardiovascular disease; Collagen; Coronary artery disease; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - pathology; diabetic cardiomyopathy; Euthanasia; Filaments; Flow velocity; Glucose; Heart; Heart diseases; High density lipoprotein; Hyperglycemia; Insulin; interventricular differences; Ischemia; Male; Mechanical properties; Muscle contraction; Myocardial Contraction; Myocytes; Myocytes, Cardiac - pathology; Myosin; Oxidative stress; Phosphorylation; Plasma; Proteins; Rats; Rats, Wistar; Rodents; Septum; single cardiomyocyte mechanics; tension-length relationship; Velocity; Ventricle; Ventricular Function; France; United States > US; Germany; Paris France; Russia; tension-length relationship; interventricular differences; diabetic cardiomyopathy; single cardiomyocyte mechanics; actin-myosin interaction; calcium transients
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031719

Type 1 diabetes (T1D) leads to ischemic heart disease and diabetic cardiomyopathy. We tested the hypothesis that T1D differently affects the contractile function of the left and right ventricular free walls (LV, RV) and the interventricular septum (IS) using a rat model of alloxan-induced T1D. Single-myocyte mechanics and cytosolic Ca concentration transients were studied on cardiomyocytes (CM) from LV, RV, and IS in the absence and presence of mechanical load. In addition, we analyzed the phosphorylation level of sarcomeric proteins and the characteristics of the actin-myosin interaction. T1D similarly affected the characteristics of actin-myosin interaction in all studied regions, decreasing the sliding velocity of native thin filaments over myosin in an in vitro motility assay and its Ca sensitivity. A decrease in the thin-filament velocity was associated with increased expression of β-myosin heavy-chain isoform. However, changes in the mechanical function of single ventricular CM induced by T1D were different. T1D depressed the contractility of CM from LV and RV; it decreased the auxotonic tension amplitude and the slope of the active tension-length relationship. Nevertheless, the contractile function of CM from IS was principally preserved.