circFAT1(e2) Inhibits Cell Apoptosis and Facilitates Progression in Vascular Smooth Muscle Cells through miR-298/MYB Axis.

Presently, as one of the three types of muscles in the human body, smooth muscle carries out many biological activities. Meanwhile, its abnormal development also leads to many diseases. Circular RNA, belonging to the noncoding RNA family, is demonstrated to function importantly in various diseases including smooth muscle. Here, we assumed circFAT1(e2) probably exhibited a primary role in vascular smooth muscle. Therefore, we conducted cell viability and cell apoptosis assay to validate the effects of circFAT1(e2) on vascular smooth muscle progression. Then, we supposed miR-298 was one target of circFAT1(e2) and executed corresponding experiments to test this hypothesis. Dual-luciferase reporter assay indicated miR-298 could bind to circFAT1(e2) and then modulated MYB level, thus regulating smooth muscle progression. Subsequently, based on the GSE41177 dataset, we identified 1982 differentially expressed genes (DEGs) in atrial fibrillation, and all DEGs were upregulated, including MYB. Finally, enrichment analysis of upregulated genes indicated that they were related to endodermal cell differentiation. The protein-protein interaction network revealed that EGFR, GNG2, and FPR2 were related to atrial fibrillation. In conclusion, our data find that circFAT1(e2) sponges miR-298 and then regulates MYB expression, thus affecting atrial fibrillation progression. Our findings provide a newly produced indicator and target for vascular smooth muscle diagnosis and treatment.

Icariin Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension via the Inhibition of TGF-ß1/Smads Pathway in Rats.

BACKGROUND: Pulmonary artery remodeling is important in the development of pulmonary artery hypertension. The TGF-ß1/Smads signaling pathway is activated in pulmonary arterial hypertension (PAH) in rats. Icariin (ICA) suppresses the TGF-ß1/Smad2 pathway in myocardial fibrosis in rats. Therefore, we investigated the role of icariin in PAH by inhibiting the TGF-ß1/Smads pathway. METHODS: Rats were randomly divided into control, monocrotaline (MCT), MCT + ICA-low, and MCT + ICA-high groups. MCT (60 mg/kg) was subcutaneously injected to induce PAH, and icariin (50 or 100 mg/kg.d) was orally administered for 2 weeks. At the end of the fourth week, right ventricular systolic pressure (RVSP) was obtained and the right ventricular hypertrophy index (RI) was determined as the ratio of the right ventricular weight to the left ventricular plus septal weight (RV/LV + S). Western blots were used to determine the expression of TGF-ß1, Smad2/3, P-Smad2/3, and matrix metalloproteinase-2 (MMP2) in lung tissues. RESULTS: Compared to the control group, RVSP and RI were increased in the MCT group (ρ < 0.05). Additionally, TGF-ß1, Smad2/3, P-Smad2/3, and MMP2 expressions were obviously increased (ρ < 0.01). Compared to the MCT group, RVSP and RI were decreased in the MCT + ICA group (ρ < 0.05). TGF-ß1, Smad2/3, P-Smad2/3, and MMP2 expressions were also inhibited in the icariin treatment groups (ρ < 0.05). Conclusions. Icariin may suppress MCT-induced PAH via the inhibition of the TGFß1-Smad2/3 pathway.

Salvianolic acid a attenuates limb ischemia/reperfusion injury in skeletal muscle of rats.

Ischemia and reperfusion(I/R) injury can cause complications in applying blood flow treatment for atherosclerosis occlusion syndrome. Platelet activation and inflammatory reaction play a role in the procession of I/R injury. This study was designed to investigate the effects of Salvianolic Acid A(SAA) on limb I/R injury via inhibition of platelet activation and inflammatory reaction. Rats were divided into sham, I/R, I/R+SAA-Low (5mg/kg) and I/R+SAA-high (10mg/kg) groups with a procession of 6h for ischemia and 24h for reperfusion in the femoral artery of the right hind limb, with the exception of the sham group. SAA was injected into the right jugular vein before reperfusion. Reperfusion recovery was monitored by Laser Doppler. HE staining, electron microscopy examination and MDA were used to evaluate the I/R injury. ELISA, Western Blot and RT-PCR were used to measure the levels of P-selectin, IL-8(KC), ICAM-1, TNF-α, IL-1ß, CK and NF-κB in plasma or tissues. Pretreatment with SAA attenuated skeletal muscle edema and mitochondria changes, and decreased the levels of MDA and CK. Meanwhile, there was significant reduction of P-selectin, KC, ICAM-1, TNF-α, IL-1ß and NF-κB with treatment of SAA. Pretreatment with SAA may attenuate the I/R injury in the skeletal muscle tissues of rats via inhibition of platelet activation and inflammatory reaction.

Salvianolic acid A protects against myocardial ischemia/reperfusion injury by reducing platelet activation and inflammation.

The aim of the present study was to investigate the protective effect of salvianolic acid A (SAA) on myocardial ischemia/reperfusion injury in rats. SAA (10 mg/kg) or Tirofiban (60 µg/kg) was administered to rats by jugular vein injection 10 min before the initiation of reperfusion. After 3 h of reperfusion, platelet aggregation was measured using an aggregometer and levels of nitric oxide (NO) were detected using an ultraviolet spectrophotometer. Serum levels of cardiac troponin T (cTnT), creatine kinase isoenzyme MB (CK-MB), p-selectin, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were also measured 3 and 24 h after reperfusion. Furthermore, morphology of the ischemic myocardium was histopathologically analyzed by hematoxylin and eosin staining, and the infarct area was evaluated by Evans blue and triphenyltetrazolium chloride staining. In rats subjected to reperfusion, it was observed that pretreatment with SAA significantly increased the survival rate (P<0.05), and that increased survival rate was due to a significant decrease in infarct size, as evidenced by significantly reduced serum levels of cTnT and CK-MB (P<0.05). In addition, decreases in infarct size occurred through the inhibition of platelet aggregation and inflammation associated with reperfusion-induced myocardial cell damage, as indicated by reduced serum levels of p-selectin, TNF-α, IL-1ß and NO. In conclusion, SAA was protective against myocardial ischemia/reperfusion injury in rats by serving antiplatelet and anti-inflammation roles.

Thymoquinone attenuates monocrotaline-induced pulmonary artery hypertension via inhibiting pulmonary arterial remodeling in rats.

BACKGROUND: Pulmonary artery remodeling induced by excess proliferation, migration and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs) is a key component in pulmonary artery hypertension (PAH). Thymoquinone (TQ) triggers cancer cells apoptosis through multiple mechanisms. In addition, TQ inhibits migration of human nonsmall-cell lung cancer cells and human glioblastoma cells. OBJECTIVES: In the current study, we investigated effects of TQ on MCT-induced PAH in rats and its underlying mechanisms. METHODS: After 2weeks of monocrotaline injection (MCT, 60mg/kg), Male Sprague-Dawley rats received TQ (8mg/kg, 12mg/kg, 16mg/kg) or olive oil per day for 2weeks. Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were examined 4weeks later. In addition, TUNEL, PCNA, α-SMA, Bax and Bcl-2 were detected by immunohistochemistry staining. Bax, Bcl-2, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) MMP2, MMP9 and activation of p38MAPK and NF-κB were assessed by Western blot. RESULTS: MCT-induced an increase in pulmonary blood pressure and right ventricular hypertrophy, which were attenuated by TQ treatment. TQ also blocked MCT-induced pulmonary arterial remodeling, proliferation of PASMCs, elevation of MMP2 and downregulation of ratio of Bax/Bcl-2, cleaved caspase-3 and cleaved PARP. Furthermore, TQ inhibited MCT-induced activation of p38MAPK and NF-κB. CONCLUSIONS: TQ ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via p38MAPK/NF-κB signaling pathway in rats.

Right coronary artery dissection and aneurysm presented as acute inferior myocardial infarction from an automobile airbag trauma.

Coronary artery dissection and aneurysm culminating in acute myocardial infarction are rare after blunt chest trauma. We are reporting a case of a previously healthy 52-year-old man who presented with right inferior lobe contusion, pleural effusion, right interlobar fissure effusion, bone fracture of right fourth rib, and acute inferior wall myocardial infarction and who experienced blunt trauma in his right chest wall by an airbag deployment in a car accident. Coronary angiography showed an aneurysm in the middle of right coronary artery with 70% afferent narrowing just distal to the aneurysm with no visible atherosclerotic lesion. A 4.0×20 mm TEXUS Liberté stent in the lesion was deployed, and a good coronary flow was obtained without residual stenosis and the aneurysm vanished.