The Impact of L Arginine's Anti-Apoptotic, Anti-Inflammatory, and Anti-Fibrotic Effects in Modulating Diabetic Cardiomyopathy: The Role of microRNA-155b in the Diagnosis of Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DC) is a serious health issue. MicroRNA-155b expression dysregulation might be involved in the fibrotic cycle in DC. L-Arginine (l-arg) is reported to have a preferable impact on the cardiovascular system. We aimed to understand the pathogenesis of DC and to detect the potential protective effect of l-arg through modulation of apoptosis, inflammation, fibrosis, and miR-155b expression. This study comprised four groups of forty adult male rats (10 rats in each group): diabetics, l-arg diabetics, l-arg, and controls. Blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), body weight, and cardiac hypertrophy index (HW/BW ratio) were assessed. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) was done. Expressions of toll-like receptor-4 (TLR4), pro-inflammatory interleukin 1 beta (IL-1β), interleukin 6 (IL-6), anti-inflammatory interleukins (IL-4, IL-13), apoptotic markers (bcl-2, bax) and microRNA-155b were measured by real-time PCR. Myocardial light, electron microscopic and morphometric studies were performed. Results showed a significant decrease in cardiac hypertrophy (HW/BW = 0.0030 ± 0.0002 mg/g), echocardiographic parameters (LVEF = 54.12 ± 1.628% and LVFS = 20.40 ± 0.541%), hemodynamic parameters (HR = 411.0 ± 9.684 bpm, SBP/DBP = 84 ± 4.998/60 ± 3.062 mmHg) and downregulation of the expression of IL-4, IL-13, IL- 1β, IL-6 and TLR4 in the l-arg diabetic group compared to diabetic rats. Additionally, restoration of normal appearance of most cardiac myofibrils, intact blood vessels, decreased cardiac fibrosis and upregulation of bax expression were observed. Expression of microRNA-155b increased by 0.007 for each gram increase in blood glucose (>1.45, it showed 100% specificity and 96.7% sensitivity). In conclusion, microRNA-155b upregulation is associated with enhancement of the transcription of inflammatory cytokines and apoptotic genes. L-arginine may be a useful protective strategy for DC through modulation of apoptosis, inflammation, and fibrosis, in addition to regulating the expression of miR-155b.