ABSTRACT
The proliferation and migration of vascular smooth muscle cells (VSMCs) are major cellular events in hypertensioninduced vascular remodeling, which is closely involved in the progression of atherosclerosis (AS). Although long noncoding RNAs (lncRNAs) are gaining recognition as novel regulators of VSMCs, their functioning and role in AS remain to be elucidated. In the present study, the role of lncRNA ENST00000430945 (lncRNA 430945) in AS was investigated. VSMCs transfected with a small interfering RNA (siRNA; si430945) and a negative control (siNC) were used. Cell Counting Kit8, woundhealing and Transwell migration arrays were performed to determine whether lncRNA 430945 influenced VSMC proliferation and migration. Furthermore, the study examined whether a correlation exists between lncRNA 430945 and the receptor tyrosine kinaselike orphan receptor 2 (ROR2) signaling pathway. It was found that the expression of lncRNA 430945 was high in human AS tissues, which in turn promoted angiotensin II (AngII)induced VSMC proliferation. Reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and western blot analyses showed that lncRNA 430945 mediated the AngIIinduced upregulation of ROR2. In addition, the microarray and RTqPCR results showed that the expression of lncRNA 430945 was increased considerably in AS tissues. The downregulation of lncRNA 430945 significantly suppressed AngIIinduced VSMC proliferation and migration. In addition, ROR2 levels in VSMCs transfected with si430945 were markedly lower than those cells transfected with siNC. Additionally, western blotting showed that lncRNA 430945 activated the signaling pathways associated with ROR2 and Ras homolog gene family member A (RhoA). The upregulation of lncRNA 430945 in AS promoted the proliferation and migration of VSMCs via activation of the ROR2/RhoA signaling pathway. Therefore, targeting ROR2 or RhoA may be a promising technique in developing therapeutic strategies for treating AS.
Subject(s)
Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , RNA, Long Noncoding/genetics , Receptor Tyrosine Kinase-like Orphan Receptors/genetics , rhoA GTP-Binding Protein/genetics , Animals , Atherosclerosis/genetics , Atherosclerosis/therapy , Cell Movement , Cell Proliferation , Gene Expression Regulation , Gene Targeting , Humans , Male , Mice , Middle Aged , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/cytology , RNA, Long Noncoding/metabolism , RNA, Small Interfering/metabolism , Receptor Tyrosine Kinase-like Orphan Receptors/metabolism , Signal Transduction , Transfection , Vascular Remodeling , rhoA GTP-Binding Protein/metabolismABSTRACT
Overwhelming clinical and epidemiological studies have identified elevated plasma total homocysteine (Hcy) as new important risk factor for atherosclerotic vascular disease. But the relationship between outcome and hyperhomocysteinemia in patients with acute myocardial infarction (AMI) has been rarely reported. This study aimed to evaluate the association between hyperhomocysteinemia and short-term outcomes of patients with AMI. Eight hundred five patients were divided into high Hcy level group (group H: N = 457) and low Hcy level group (group L: N = 348) according to the plasma Hcy levels of 15 mmol/L. The comparisons were made between 2 groups in the following aspects: sex, hypertension, diabetes, hyperlipidemia, the time for symptom from onset to percutaneous coronary intervention, homoccyteine, creatine phosphokinase isoenzyme (creatine kinase myocardial band), and the incidence of 30-day adverse events. The incidences of heart failure, cardiac rupture, death, and the total adverse cardiovascular events were statistically significantly higher in group H than in group L. But the incidence of postoperative angina pectoris and reinfarction was similar between groups. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to the age and the level of Hcy. An elevated plasma total Hcy level in patients with AMI experienced pemutaneous coronary intervention may be related to the short-term outcomes. An elevated high plasma Hcy level also seems to be an independent predictor of 30-day cardiovascular events in patients with AMI.
Subject(s)
Cardiovascular Diseases/epidemiology , Hyperhomocysteinemia/epidemiology , Myocardial Infarction/physiopathology , Percutaneous Coronary Intervention/methods , Aged , Cardiovascular Diseases/physiopathology , Female , Follow-Up Studies , Humans , Incidence , Logistic Models , Male , Middle Aged , Myocardial Infarction/surgery , Prospective Studies , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Although statins are generally well-tolerated drugs, recent cases of drug-induced liver injury associated with their use have been reported. A 52-year-old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.