ABSTRACT
BACKGROUND: MicroRNA-21 (miR-21) is related to hypertension and cardiac remodelling. Left atrium (LA) dilation is highly sensitive to small haemodynamic changes in the left ventricle (LV) that are induced by hypertension. This study aimed to elucidate the relationship between miR-21 expression and LA dilation in elderly patients with essential hypertension (EH). METHODS: In this cross-sectional study, one hundred elderly patients with EH were recruited for the study. According to their left atrium diameters (LADs), the patients were divided into the LA dilation group [42 patients (42%)] and the no-LA dilation group [58 patients (58%)]. The serum levels of miR-21 and chemical biomarkers used in the clinic, such as creatinine, blood urea nitrogen, uric acid, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol, Lp(a), apolipoprotein A1 (apoA1), and apolipoprotein B, were measured. All the patients underwent echocardiographic examination, and the LAD, interventricular septum (IVS), right atrium diameter (RAD), right ventricle diameter (RVD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were measured. RESULTS: The levels of miR-21 [8.02 (5.21, 14.39) vs. 6.05 (3.81, 8.95), P = 0.011] and LVEF (67.02 ± 3.82 vs. 64.14 ± 4.43, P = 0.001) were higher in the LA dilation group. The levels of creatinine [70.40 (64.45, 80.15) vs. 63.9(60.1, 73.43)], P = 0.020] were higher in the no-LA dilation group. The levels of HDLC (r = - 0.209, P = 0.037), apoA1 (r = -0.269, P = 0.007) and RAD (r = 0.203, P = 0.043) were significantly correlated with miR-21 expression. The LAD was significantly correlated with the RAD (r = 0.287, P = 0.004), RVD (r = 0.450, P < 0.001), LVEDD (r = 0.248, P = 0.013) and LVEF (r = 0.232, P = 0.020). Multivariate logistic regression revealed that miR-21 significantly influenced LA dilation in elderly patients with EH (P < 0.05). CONCLUSIONS: Circulating serum levels of miR-21 are increased in elderly patients with EH with LA dilation. miR-21 levels are significantly correlated with LA dilation in elderly patients with EH, and miR-21 may be a factor related to the clinical pathophysiological occurrence of and treatment for the progression of hypertension-related early heart damage in EH patients.
ABSTRACT
Recently, hypoglycemic drugs belonging to sodium-glucose cotransporter 2 inhibitors (SGLT2i) have generated significant interest due to their clear cardiovascular benefits for heart failure with preserved ejection fraction (HFpEF) since there are no effective drugs that may improve clinical outcomes for these patients over a prolonged period. But, the underlying mechanisms remain unclear, particularly its effects on ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death during heart failure (HF). Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin. Data are available via ProteomeXchange with identifier PXD029031. The ferroptosis was evaluated with the levels of acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, ferritin heavy chain 1, transferrin receptor, Ferroportin 1, iron, glutathione, malondialdehyde, and 4-hydroxy-trans-2-nonenal. These findings highlight the fact that targeting ferroptosis may serve as a cardioprotective strategy for HFpEF prevention and suggest that canagliflozin may exert its cardiovascular benefits partly via its mitigation of ferroptosis.
