RESUMEN
Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin-1, an actin-binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin-1 in ADMA-induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty-two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin-1 small hairpin RNA to interrupt the expression of profilin-1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin-1 was tested using real-time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin-1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p < 0.05). In vitro, studies showed ADMA-induced profilin-1 expression in a concentration- and time-dependent manner in RASMCs (p < 0.05), concomitantly with promoting the proliferation of RASMCs. Furthermore, ADMA-mediated proliferation of RASMCs and upregulation expression of profilin-1 were inhibited by blockade of the JAK2/STAT3 pathway or knockdown of profilin-1. Profilin-1 implicated in the ADMA-mediated vascular lesions in hypertension.
Asunto(s)
Arginina/análogos & derivados , Endotelio Vascular/efectos de los fármacos , Hipertensión/etiología , Miocitos del Músculo Liso/efectos de los fármacos , Profilinas/fisiología , Animales , Arginina/farmacología , Arginina/fisiología , Proliferación Celular , Endotelio Vascular/patología , Humanos , Miocitos del Músculo Liso/patología , RatasRESUMEN
BACKGROUND: Brugada syndrome (BrS) is an inherited disease characterized by an electrocardiogram (ECG) with a coved-type ST-segment elevation in the right precordial leads (V1-V3), which predisposes to sudden cardiac death (SCD) due to polymorphic ventricular tachycardia or ventricular fibrillation in the absence of structural heart disease. We report the case of a 29-year-old man with out-of-hospital cardiac arrest. BrS is associated with a high incidence of SCD in adults, and increasing the awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving. CASE SUMMARY: A 29-year-old man suffered from out-of-hospital cardiac arrest, and after defibrillation, his ECG demonstrated a coved-type elevated ST segment in V1 and V2. These findings were compatible with type 1 Brugada pattern, and ECG of his brother showed a type 2 Brugada pattern. The diagnosis was BrS, NYHF IV, multiple organ dysfunction syndrome, sepsis, and hypoxic ischemic encephalopathy. The patient had no arrhythmia episodes after discharge throughout a follow-up period of 36 mo. CONCLUSION: Increasing awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving.
RESUMEN
Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP450) products of arachidonic acid and EETs are endogenous lipid mediators synthesized by the vascular endothelium which perform important biological functions, including vasodilation, anti-inflammation, antimigratory, and cellular signaling regulations. However, EETs are rapidly degraded by soluble epoxide hydrolase (sEH) to the corresponding diols: dihydroxyeicosatrienoic acids (DHETs), which have little active in causing vasorelaxation. A number of studies have supported that the inhibition of sEH (sEHIs) had cardiovascular protective effects in hypertension, cardiac hypertrophy, atherosclerosis, ischemia-reperfusion injury, and ischemic stroke. Moreover, sEHIs could slow the progression of inflammation, protect end-organ damage and prevent ischemic events, also, attenuate endothelial dysfunction, suggesting that the pharmacological blockade of sEH might provide a broad and novel avenue for the treatment of many cardiovascular diseases.
Asunto(s)
Fármacos Cardiovasculares/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/fisiopatología , Inhibidores Enzimáticos/farmacología , Epóxido Hidrolasas/efectos de los fármacos , Epóxido Hidrolasas/fisiología , Animales , Isquemia Encefálica/enzimología , Isquemia Encefálica/genética , Cardiomegalia/enzimología , Cardiomegalia/genética , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/genética , Humanos , Hipertensión/enzimología , Polimorfismo Genético , Daño por Reperfusión/enzimología , Daño por Reperfusión/genética , Riesgo , Accidente Cerebrovascular/enzimología , Accidente Cerebrovascular/genéticaRESUMEN
Profilin-1, a regulator of actin polymerization, has recently been linked to vascular hypertrophy and remodeling. Whether profilin-1 is involved in angiotensin (Ang) II-induced proliferation of vascular smooth muscle cells leading to vascular remodeling in hypertension remains unclear. The present study was designed to analyze the correlation of profilin-1 and vascular remodeling during hypertension and to evaluate the role of profilin-1 in proliferation of vascular smooth muscle cells and the underlying mechanisms. The vascular morphology and the expression of profilin-1 in arterial tissues of spontaneously hypertensive rats and Wistar-Kyoto rats were assessed. The profilin-1 expression was significantly increased concomitantly with definite vascular remodeling by evaluating the media thickness, lumen diameter, media thickness-to-lumen diameter ratio and mean nuclear area in artery media in spontaneously hypertensive rats, which was inhibited by treatment with losartan. In cultured rat aortic smooth muscle cells (RASMCs), Ang II induced profilin-1 expression in a dose- and time-dependent manner. Knockdown of profilin-1 using small hairpin RNA inhibited Ang II-induced proliferation of RASMCs. Moreover, blockade of JAK2/STAT3 signaling pathway also inhibited Ang II-induced proliferation of RASMCs and profilin-1 expression. These results suggest that profilin-1 mediates the proliferation of RASMCs induced by Ang II via activation of Ang II type 1 receptor/JAK2/STAT3 signaling pathway, which may contribute to vascular remodeling in hypertension.
Asunto(s)
Angiotensina II/farmacología , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Profilinas/metabolismo , Angiotensina II/metabolismo , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Presión Sanguínea/efectos de los fármacos , Procesos de Crecimiento Celular/efectos de los fármacos , Procesos de Crecimiento Celular/fisiología , Células Cultivadas , Técnicas de Silenciamiento del Gen/métodos , Hipertensión/metabolismo , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/metabolismo , Losartán/farmacología , Masculino , Arterias Mesentéricas/citología , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Profilinas/antagonistas & inhibidores , Profilinas/genética , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
PURPOSE: To determine the indications and benefits of ectopic implantation in the salvage of amputated thumb. BASIC PROCEDURES: Two cases of avulsed amputated thumbs were temporarily ectopically implanted onto the forearm and foot, with microvascular anastomoses. When the stump condition allowed, and the soft-tissue defects were repaired, the ectopic implanted thumbs were replanted to their anatomic positions. RESULTS: Both thumbs survived the temporary ectopic implantation and second-stage replantation. The length of the thumbs was maintained, and the thumbs regained their function in 16- and 10-week follow-ups. CONCLUSIONS: Temporary ectopic implantation of amputated parts provides an innovative procedure for the salvage of amputated thumbs under special circumstances. Although this procedure is very demanding, it does deserve special consideration in reconstructive microsurgery, since it offers the possibility to salvage amputated thumbs with extensive soft tissue loss of the hand, by preserving the anatomy and restoring the function of severely injured hands.