Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats.

BACKGROUND/AIMS: Myocardial infarction (MI) increases myocardial fibrosis (MF) and subsequent cardiac remodeling. Cholecystokinin octapeptide (CCK-8) is expressed in cardiomyocytes and plays an important role in cardiovascular regulation. In this study, we intend to use a rat model of myocardial infarction to evaluate the effects of CCK-8 on myocardial fibrosis and cardiac remodeling. METHODS: Male Sprague-Dawley rats were separated into 3 groups: sham operation, MI + NaCl, and MI + CCK-8. All rats were subjected to left coronary artery ligation to induce MI or sham operation and then treated with CCK-8 or saline for 28 days. After 4 weeks, echocardiography was performed to assess cardiac function and myocardial fibrosis was evaluated using H&E and Masson's Trichrome-stained sections. The levels of BNP, CCK-8 in the plasma of all rats were detected by ELISA; RNA sequencing (RNA-seq) analysis was also adapted to detect differentially expressed genes in myocardial tissues of each group. Myocardial expression of fibrosis markers was analyzed by western blotting, immunohistochemistry and qRT-PCR. RESULTS: CCK-8 was demonstrated to improve left ventricular function and results of H&E staining, Masson's trichrome staining, immunohistochemistry and western blotting showed that CCK-8 attenuated MF. Gene expression profiles of the left ventricles were analysed by RNA-seq and validated by qRT-PCR. Cardiac fibrosis genes were downregulated by CCK-8 in the left ventricle. SIGNIFICANCE: CCK-8 can alleviate fibrosis in the noninfarcted regions and delay the left ventricular remodeling and the progress of heart failure in a MI rat model.

Inhibition of vascular calcification by microRNA-155-5p is accompanied by the inactivation of TGF-ß1/Smad2/3 signaling pathway.

Vascular calcification (VC) is a vital factor for cardiovascular morbidity and mortality. Accumulating data suggest that microRNA (miR) is implicated in the VC. The main purpose of this study is to study the influence of miR-155-5p overexpression on VC development in vitro and in vivo. Immunofluorescence staining, real-time PCR, alizarin red staining, alkaline phosphatase (ALP) activity assay, western blot, luciferase assay, hematoxylin-eosin (HE), Masson's trichrome staining, and calcium content assay were used in this research. The results showed that miR-155-5p was decreased in the rat vascular smooth muscle cells (rVSMCs) undergoing calcification in vitro. MiR-155-5p overexpression reversed the increase of calcification and ALP activity in calcified cells. Further, overexpression of miR-155-5p inhibited the transforming growth factor-ß1 (TGF-ß1)/Smad2/3 signaling pathway, as evidenced by decreased protein expression of TGF-ß1, pSmad-2 and pSmad-3 in rVSMCs. MiR-155-5p was showed to target Smad2 directly. Moreover, miR-155-5p upregulation reduced vascular thickening, fibrosis and calcium content of aorta abdominalis in CaCl2-mediated VC model. Collectively, our results suggest that miR-155-5p overexpression may inhibit VC development through suppressing TGF-ß1/Smad2/3 signaling pathway in vivo and in vitro, indicating that miR-155-5p may act as a potential therapeutic target for VC-related disease.

The Relationship of Appetite-Regulating Hormones in the Development of Cardiac Cachexia.

The physiological control of appetite regulation involves circulating hormones with orexigenic (ghrelin) and anorexigenic (cholecystokinin) properties that induce alterations in energy intake via perceptions of hunger and satiety. We sought to investigate the relationship between appetite-regulating hormones and the cachexia associated with chronic heart failure.We randomized male Sprague-Dawley rats into myocardial infarction (MI) or sham operation (SO) groups. The levels of brain natriuretic peptide (BNP), cholecystokinin (CCK) and ghrelin in the plasma of all rats were detected by enzyme-linked immunosorbent assay (ELISA); the expression of BNP, CCK, and ghrelin in the myocardial tissue of all rats were detected by western blotting, immunohistochemistry, real-time polymerase chain reaction (PCR); myocardial morphology was assessed by microscopy.Plasma BNP and CCK levels in the cardiac cachexia (CC) groups and the heart failure non-cachexia (HF-nc) groups were significantly higher than those in the control groups (P < 0.01), and the expression of BNP and CCK in the myocardial tissue of rats: in CC groups and HF-nc groups were increased compared with the corresponding control groups (P < 0.01). In contrast, Plasma and cardiac expression of ghrelin decreased compared with the sham group (P < 0.01). Furthermore, plasma CCK levels were positively correlated with BNP concentrations (P < 0.001) and significantly negatively correlated with the ejection fraction (P < 0.001) in model animals; plasma ghrelin levels were negatively associated with BNP levels (P = 0.0023) and positively associated with ejection fraction (P = 0.0042).The appetite-regulating hormones (ghrelin and CCK) may present as a potential significant biomarker for cachexia associated with chronic heart failure.

Cardioprotective effects of baicalein on heart failure via modulation of Ca(2+) handling proteins in vivo and in vitro.

AIMS: Baicalein is a widely used Chinese herbal medicine extracted from Labiatae plants Scutellaria baicalensis Georgi's dry root, which has multiple pharmacological activities. However, the precise mechanism of baicalein against myocardial remodeling remains poorly understood. The aim of our study was to investigate the underlying mechanism of baicalein treatment in rats model of heart failure (HF) and rat myocardial cells (H9C2). MAIN METHODS: HF model was established by abdominal aorta constriction in rats and incubation with 50µM isoproterenol for 48h in H9C2 cells. Various molecular biological experiments were performed to assess the effects of baicalein on cardiac function, myocardial remodeling, apoptosis and Ca(2+) handling proteins. KEY FINDINGS: In the present study, first we found that baicalein alleviated HF in vivo. Additionally, treatment with baicalein inhibited the myocardial fibrosis, restrained the expression and activity of MMP2 and MMP9, and suppressed apoptosis in heart tissue. Moreover, baicalein could inhibit the cardiac myocyte hypertrophy and apoptosis induced by isoproterenol in vitro. Finally we found that baicalein could modulate the expressions and activities of Ca(2+) handling proteins, including downregulation of phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and expression of Na(+)/Ca(2+)-exchangers (NCX1), upregulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) and ryanodine receptor 2 (RYR2). Baicalein also restrained the decreased SERCA activity induced by aortic banding. SIGNIFICANCE: Our studies suggested that baicalein alleviated myocardial remodeling and improved cardiac function via modulation of Ca(2+) handling proteins, which may be a potential phytochemical flavonoid for therapeutics of HF.

Extraction of Iron from the Rabbit Anterior Chamber with Reverse Iontophoresis.

Ocular siderosis is a common eye disease caused by retention of an iron-containing intraocular foreign body in the eye. Iron-containing intraocular foreign bodies may cause severe inflammatory reaction and affect visual function. Currently the optimal treatment method of ocular siderosis is a moot point. This study used the reverse iontophoresis technique to noninvasively extract iron from the rabbit anterior chamber. By slit lamp observation and histological examination, reverse iontophoresis treatment has a good effect on ocular siderosis. Reverse iontophoresis seems to be a noninvasive and promising approach to extract iron from the anterior chamber to treat ocular siderosis.

Serum parathyroid hormone as a potential novel biomarker of coronary heart disease.

OBJECTIVE: This study aimed to evaluate the relationships between serum parathyroid hormone (PTH) and coronary heart disease (CHD). METHODS: From July 2011 to February 2013, a total of 79 CHD patients and 94 normal control patients with ages ranging from 25 to 79 years were included in this study. Serum PTH level and common risk factors of CHD (age, gender, cholesterol, glycosylated hemoglobin [HbA1c], blood pressure [BP], history of diabetes, smoking, and body mass index) were investigated. Pearson's correlation and multiple regression analyses were used to evaluate the relationships between serum PTH level and CHD risk factors. All statistical analyses were performed using the SPSS 18.0 software. RESULTS: RESULTS from Pearson's correlation analysis indicated that age, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), HbA1c, history of smoking, and serum PTH level were risk factors for CHD (all p<0.05). Serum PTH levels were positively correlated with DBP (r=0.256, p=0.010) and HbA1c (r=0.223, p=0.003), while not being related to other risk factors of CHD (all p>0.05). Multiple linear regression analysis showed that SBP, DBP, LDL-c, and HDL-c may be important determinants of CHD (all p<0.05). Further, serum PTH level is also an independent risk factor for CHD (p<0.001). CONCLUSION: Our results provide evidence that serum PTH level may be involved in the pathogenesis of CHD. Thus, PTH could be used as an important biomarker in the diagnosis of CHD.