The relationship between serum miR-21 levels and left atrium dilation in elderly patients with essential hypertension.

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.

Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction.

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.

Protective effect of miRNA-containing extracellular vesicles derived from mesenchymal stromal cells of old rats on renal function in chronic kidney disease.

INTRODUCTION: Mesenchymal stromal cells (MSCs) play an important role in the prevention of cell and tissue fibrosis. Senescence may decrease the function of MSCs during recovery from tissue and organ damage. Extracellular vesicles (EVs) released from MSCs contribute to the repair of kidney injury. We explored the influence of senescence on EVs derived from MSCs (MSC-EVs) and detected the protective effects of MSC-EVs expressing low levels of miR-294/miR-133 derived from old rats against chronic kidney disease (CKD). METHODS: The effects of MSC-EVs derived from 3-month-old and 18-month-old male Fisher 344 rats on renal fibrosis were explored in a unilateral ureteral obstruction (UUO) model. pLV-miR-294/pLV-miR-133 mimic/inhibitor were injected into young and old rats before UUO to detect the effects of miR-294/miR-133, which were decreased in MSC-EVs and sera from old rats, on renal function in CKD. Transforming growth factor-ß1 (TGF-ß1)-induced human renal proximal tubular epithelial (HK2) cells were used to imitate the pathological process of renal fibrosis in vitro. Western blotting was used to assess the expression of epithelial/mesenchymal markers and phosphorylation of proteins in HK2 cells. RESULTS: The inhibition of UUO-induced CKD by MSC-EVs was weaker in old rats than in young rats. Downregulation of miRNAs (miR-294 and miR-133) in both MSC-EVs and sera from old rats obviously attenuated UUO-induced renal injury in old rats. miR-294 and miR-133 overexpression mitigated TGF-ß1-mediated epithelial-mesenchymal transition (EMT) in HK2 cells, and the obvious increase in the phosphorylation of both SMAD2/3 and ERK1/2 induced by TGF-ß1 was prevented in miR-294- and miR-133-overexpressing HK2 cells. CONCLUSIONS: The ability of MSC-EVs to inhibit renal fibrosis decreased with age. miR-294/miR-133 in MSC-EVs and sera had an important effect on renal fibrosis in old rats and on EMT in HK2 cells. Furthermore, miR-294/miR-133 overexpression prevented SMAD2/3 and ERK1/2 phosphorylation in HK2 cells during TGF-ß1-mediated EMT. These findings show that miR-294/miR-133 may be therapeutic in renal fibrosis and related renal dysfunction in elderly individuals.

No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study.

BACKGROUND: Reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient. METHODS: In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of "compound reserpine and triamterene tablets (CRTTs)" for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected. RESULTS: From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users (P = 0.7). The majority of study subject had a depression score < 53 (87.6% in reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users. CONCLUSIONS: There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered; and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

Serotype distribution and antimicrobial resistance patterns in Streptococcus pneumoniae isolates from hospitalized pediatric patients with respiratory infections in Shanghai, China.

BACKGROUND: Surveillance for pneumococcal respiratory illness was conducted in children hospitalized at Affiliated Pediatric Hospital of Fudan University in Shanghai from August 2000 to August 2001. METHODS: Sputum cultures were obtained from pediatric patients admitted with pneumonia or respiratory distress by tracheal aspirate. Blood cultures were also performed on a subset of patients. All pneumococcal isolates were serotyped and tested for antibiotic susceptibility. In addition clinical information on the patients including prior antibiotic history was abstracted. Streptococcus pneumoniae tracheal isolations were attempted in a total of 1013 pediatric patients hospitalized during this period. Among these samples 112 specimens were S. pneumoniae-positive. These positive isolates underwent serotyping and antibiotic susceptibility testing. RESULTS: Five serotypes (19F, 23F, 6A, 14, 6B) of S. pneumonia accounted for 81% (91 of 112 cases). Other serotypes accounted only for 12% (13 of 112 cases), and 7% (8 of 112 cases) of isolates could not be typed by quelling test. Only one blood culture isolate was positive, probably reflecting the frequent use of antibiotic treatment before hospitalization. Fifty-one and 8.0% of isolates had intermediate and high level penicillin resistance, respectively. Fifty-eight percent were resistant to ampicillin, 6.6% to cefazolin, 25.0% to cefaclor, 6.6% to ceftriaxone, 85.7% to erythromycin, 66.7% to clindamycin and 28.2% to chloramphenicol. Among 66 isolates that were not susceptible to penicillin, serotype 19F was the most common, followed by 23F and 14. CONCLUSION: S. pneumoniae is a common cause of respiratory illness requiring hospitalization in young children in Shanghai, with antibiotic resistance increasingly common. Five serotypes account for most disease.

Circadian rhythm in the cardiovascular system: chronocardiology.

BACKGROUND: We reviewed recent progress in the study of the chronobiological aspects of the cardiovascular system. METHODS: Medline was used as the main search tool, and the full texts of selected papers were obtained. RESULTS: More than 300 references were found, and 52 of them, representing the major findings in this field, were included in the reference list. Results of these studies confirm that most cardiovascular physiological parameters (such as heart rate, blood pressure, electrocardiogram indices) and pathophysiological events (myocardial ischemia/infarction, sudden cardiac death) show circadian rhythms. Results also suggest that consideration of these rhythms is important for the diagnosis and treatment of cardiovascular disorders and that restoration of normal circadian rhythms may be associated with clinical improvement. CONCLUSION: The study of circadian rhythms in the cardiovascular system is emerging as an important area of investigation because of its potential implications for patient management.

Circadian rhythm in the cardiovascular system: considerations in non-invasive electrophysiology.

Most cardiovascular activities show a circadian rhythm, as do electrophysiological phenomenon. Under the influence of both external stimuli and endogenous homoeostatic mechanisms, cardiac electrophysiological properties change diurnally and enable the cardiovascular system adapt to rest-exercise cycles. According to recent reports, almost all non-invasive electrophysiological phenomena, such as electrocardiographic indices, cardiac refractoriness and conduction, pacing and defibrillation threshold, heart rate variability indices, and even Q-T dispersion and T-wave alternans, show diurnal variability. Furthermore, many of these changes are clinically significant and may affect results of some diagnostic studies. These characteristics of the cardiovascular system require us keep in mind the "time" factor any time we analyze electrophysiological results and make clinical decisions.