M3 subtype of muscarinic acetylcholine receptor inhibits cardiac fibrosis via targeting microRNA-29b/beta-site app cleaving enzyme 1 axis.

Background: Previous studies have confirmed that choline exerts anti-fibrotic effect in the heart by activating the M3 subtype of muscarinic acetylcholine receptor (M3 receptor), but the mechanism remains to be clarified. MicroRNA-29b (miR-29b) plays an important role in the fibrotic process and can directly target collagen to resist myocardial fibrosis. This study investigated whether miR-29b is involved in the anti-fibrotic effect of activating M3 receptor. Methods: Proliferation of cardiac fibroblasts was induced by transforming growth factor (TGF)-ß1 in vitro. The expression of miR-29b in cardiac fibroblasts was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Protein levels of collagens I, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA) and beta-site app cleaving enzyme 1 (BACE1) were determined by Western blot analysis. Fibroblast-myofibroblast transition was identified by immunofluorescence staining. Proliferation and migration of cardiac fibroblasts as indicated by transwell and scratch assays. Results: The expression of miR-29b decreased when treated with TGF-ß1 (P=0.0389) and increased after choline stimulated (P=0.0001). Overexpression of miR-29b could reverse the high expression of collagen I (P<0.0001), α-SMA (P=0.0007), and CTGF (P=0.0038) induced by TGF-ß1, whereas inhibition of miR-29b had a tendency to even further increase the expression of fibrosis markers. Meanwhile, inhibition of miR-29b could reverse the anti-fibrotic effect of choline, increasing the expression of collagen I (P=0.0040), α-SMA (P=0.0001), and CTGF (P=0.0185), and promoting the fibroblast proliferation and migration. Moreover, BACE1 protein level, increased after TGF-ß1 treatment (P=0.0037) and reversed by overexpression of miR-29b (P=0.0493). Choline could reduce the increase of BACE1 induced by TGF-ß1 (P=0.0264), and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) increased the expression of BACE1 (P=0.0060). Furthermore, overexpression of BACE1 could reverse the protective effect of miR-29b in cardiac fibrosis, increasing the protein level of collagen I (P=0.0404). Conclusions: The results suggested that M3 receptor activation could exert cardioprotective effects in cardiac fibrosis by mediating miR-29b/BACE1 axis.

CDR1as promotes arrhythmias in myocardial infarction via targeting the NAMPT-NAD+ pathway.

Cardiac ventricular arrhythmia triggered by acute myocardial infarction (AMI) is a major cause of sudden cardiac death. We have reported previously that an increased serum level of circular RNA CDR1as is a potential biomarker of AMI. However, the possible role of CDR1as in post-infarct arrhythmia remains unclear. This study in MI mice investigated the effects and underlying mechanism of CDR1as in ventricular arrhythmias associated with MI. We showed that knockdown of CDR1as abbreviated the duration of the abnormally prolonged QRS complex and QTc intervals and decreased susceptibility to ventricular arrhythmias. Optical mapping demonstrated knockdown of CDR1as also reduced post-infarct arrhythmia by increasing the conduction velocity and decreasing dispersion of repolarization. Mechanistically, CDR1as led to the depletion of NAD+ and caused mitochondrial dysfunction by directly targeting the NAMPT protein and repressing its expression. Moreover, CDR1as aggravated dysregulation of the NaV1.5 and Kir6.2 channels in cardiomyocytes, a change which was alleviated by the replenishment of NAD+. These findings suggest that anti-CDR1as is a potential therapeutic approach for ischemic arrhythmias.

Aloe-emodin ameliorated MI-induced cardiac remodeling in mice via inhibiting TGF-ß/SMAD signaling via up-regulating SMAD7.

BACKGROUND: Aloe-emodin (AE), a natural anthraquinone extract from traditional Chinese medicinal plants, has been certified to protect against acute myocardial ischemia. However, its effect on cardiac remodeling after chronic myocardial infarction (MI) and the possible mechanism remain unclear. PURPOSE: This study investigated the effect of AE on cardiac remodeling and oxidative damage induced by myocardial infarction (MI) in vitro and explored the underlying mechanisms. METHODS: Echocardiography and Masson staining were used to demonstrate myocardial dysfunction and fibrosis. Cell apoptosis was detected by TUNEL staining. The expressions of fibrosis-related factors such as type I collagen, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) were detected by Western blot. RESULTS: Our data demonstrated that AE treatment significantly improved cardiac function, reduced structural remodeling, and reduced cardiac apoptosis and oxidative stress in mice with myocardial infarction. In vitro, AE could protect neonatal mouse cardiomyocytes (NMCM) from angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and apoptosis, and significantly inhibited (p < 0.05) Ang II-induced reactive oxygen species (ROS) increase. Furthermore, AE treatment significantly reversed the Ang ii-induced upregulation. CONCLUSION: In summary, our work reveals for the first time that AE activates the TGF-ß signaling pathway by up-regulating Smad7 expression, which in turn regulates the expression of fibrosis-related genes, ultimately improving cardiac function, inhibiting the development of cardiac fibrosis and hypertrophy in rats with chronic MI.

Particle removal by vegetation: comparison in a forest and a wetland.

Vegetation collection is one of the most effective scavenging methods but relevant studies are limited. It can be described by some abstract parameters such as collection rates and deposition fluxes within the canopy. In order to estimate the dry deposition within the canopy of particular matters (PMs) in Beijing, a highly particle-polluted city, and reveal the PM pollution-removal abilities of plants in wetlands and forests, concentration and meteorological data were collected during the daytime in an artificial forest and a wetland in the Olympic Park in Beijing. The dry depositions within the canopy and vegetation collection rates were calculated by a well-developed model and validated by measured deposition fluxes in 11 random experiment days. The experiment year was divided into three plant growth stages based on canopy density, and the day was divided into four different times. Two heights, 10 and 1.5 m, were defined in the forest while in the wetland, 0.5 and 1.5 m were defined. The results showed that in Beijing, the most severe pollution by PMs occurs in the non-leaf stage (NS), and the full-leaf stage (FS) is the cleanest stage. In NS, namely winter, more fossil fuel was used for worms in Beijing and peripheral areas and this might be the reason for the serious pollution condition. Within the canopy, PM deposition fluxes in the wetland are more than those in the forest, but the vegetation collection rates of the forest are higher. The lower temperature conditions led to more dry deposition, and the larger canopy contributed to the higher collection rates. During the daytime, over the year, the deposition of PM10 in three plant growth stages is NS ≥ half-leaf stages (HS) ≥ FS, whereas the deposition of PM2.5 is NS ≥ FS ≥ HS, and during the daytime, the maximum deposition fluxes occur in 6:00-9:00 in the wetland while the minimum deposition values occur in 15:00-18:00. This phenomenon was related to the temporal variation of particle concentration.

Removal efficiency of particulate matters at different underlying surfaces in Beijing.

Particulate matter (PM) pollution has been increasingly becoming serious in Beijing and has drawn the attention of the local government and general public. This study was conducted during early spring of 2013 and 2014 to monitor the concentration of PM at three different land surfaces (bare land, urban forest, and lake) in the Olympic Park in Beijing and to analyze its effect on the concentration of meteorological factors and the dry deposition onto different land cover types. The results showed that diurnal variation of PM concentrations at the three different land surfaces had no significant regulations, and sharp short-term increases in PM10 (particulate matter having an aerodynamic diameter <10 µm) occurred occasionally. The concentrations also differed from one land cover type to another at the same time, but the regulation was insignificant. The most important meteorological factor influencing the PM concentration is relative humidity; it is positively correlated with the PM concentration. While in the forests, the wind speed and irradiance also influenced the PM concentration by affecting the capture capacity of trees and dry deposition velocity. Other factors were not correlated with or influenced by the PM concentration. In addition, the hourly dry deposition in unit area (µg/m(2)) onto the three types of land surfaces and the removal efficiency based on the ratio of dry deposition and PM concentration were calculated. The results showed that the forest has the best removal capacity for both PM2.5 (particulate matter having an aerodynamic diameter <2.5 µm) and PM10 because of the faster deposition velocity and relatively low resuspension rate. The lake's PM10 removal efficiency is higher than that of the bare land because of the relatively higher PM resuspension rates on the bare land. However, the PM2.5 removal efficiency is lower than that of the bare land because of the significantly lower dry deposition velocity.