Angiotensin II (Ang II) is a main pathophysiological culprit peptide for hypertension and atherosclerosis by causing vascular smooth muscle cell (VSMC) proliferation and migration. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, is currently used for the treatment of type-2 diabetes, and is believed to have beneficial effects for cardiovascular diseases. However, the vascular protective mechanisms of GLP-1 receptor agonists remain largely unexplained. In the present study, we examined the effect of exendin-4 on Ang II-induced proliferation and migration of cultured rat aortic smooth muscle cells (RASMC). The major findings of the present study are as follows: (1) Ang II caused a phenotypic switch of RASMC from contractile type to synthetic proliferative type cells; (2) Ang II caused concentration-dependent RASMC proliferation, which was significantly inhibited by the pretreatment with exendin-4; (3) Ang II caused concentration-dependent RASMC migration, which was effectively inhibited by the pretreatment with exendin-4; (4) exendin-4 inhibited Ang II-induced phosphorylation of ERK1/2 and JNK in a pre-incubation time-dependent manner; and (5) U0126 (an ERK1/2 kinase inhibitor) and SP600125 (a JNK inhibitor) also inhibited both RASMC proliferation and migration induced by Ang II stimulation. These results suggest that exendin-4 prevented Ang II-induced VSMC proliferation and migration through the inhibition of ERK1/2 and JNK phosphorylation caused by Ang II stimulation. This indicates that GLP-1 receptor agonists should be considered for use in the treatment of cardiovascular diseases in addition to their current use in the treatment of diabetes mellitus.
Purpose: To evaluate the effect of vessel calcification on in-stent restenosis (ISR) after drug-coated stent (DCS) placement in the femoropopliteal segment. Materials and Methods: A retrospective multicenter study was undertaken involving 220 consecutive symptomatic patients (mean age 73.1±8.3 years; 175 men) with femoropopliteal lesions in 230 limbs treated with the Zilver PTX DCS and having duplex surveillance after the endovascular procedures. Mean lesion length was 16.4±9.8 cm (range 2–40); there were 104 (45.2%) total occlusions and 68 (29.6%) in-stent restenoses (ISR). Twenty (8.7%) vessels had no runoff. The majority of lesions (148, 64.3%) were calcified according to the peripheral arterial calcium scoring system (PACSS). Primary patency was evaluated by duplex. Lesions were classified as either PACSS 0–2 (none or unilateral wall calcification) or PACSS 3 and 4 (bilateral wall calcification). Multivariate analysis was performed to identify variables associated with ISR; the results are given as the hazard ratio (HR) and 95% confidence interval (CI). Results: The 1-, 2-, and 5-year primary patency and freedom from clinically-driven target lesion revascularization estimates were 75.9%, 63.6%, and 45.0%, and 84.7%, 73.7%, and 54.2%, respectively. Major amputations were performed on 4 limbs during follow-up. In multivariate analysis, vessel calcification (adjusted HR 1.718, 95% CI 1.035 to 2.851, p=0.036) was significantly correlated with the occurrence of ISR, along with lesion length (adjusted HR 1.041, 95% CI 1.013 to 1.070, p=0.003), and cilostazol administration (adjusted HR 0.476, 95% CI 0.259 to 0.876, p=0.017). Conclusion: This study suggested that bilateral vessel wall calcification was an independent risk factor for ISR in complex femoropopliteal lesions after Zilver PTX DCS placement, along with lesion length; cilostazol administration had a protective effect.
With each successive update of the cardiopulmonary resuscitation (CPR) guidelines, the role of dispatchers in sudden cardiac arrest (CA) has grown. Dispatchers instruct callers in how to perform CPR until the arrival of emergency medical service (EMS) professionals. This is widely known as telephone CPR (TCPR) or dispatch-assisted CPR (DACPR). Studies have shown the efficacy of TCPR in increasing the survival rate of sudden CA. The TCPR process, however, is challenging and needs to be constantly evaluated and refined in order to improve the survival rate of sudden CA victims throughout the world. In this review article, the current status, challenges, and future perspectives of TCPR are discussed with a view to providing a research foundation from which to launch further studies into the effective role of dispatchers in sudden CA.
AimBystander cardiopulmonary resuscitation (CPR) is essential for improving the outcomes of sudden cardiac arrest patients. It has been reported that dispatch‐assisted CPR (DACPR) accounts for more than half of the incidence of CPR undertaken by bystanders. Its quality, however, can be suboptimal. We aimed to measure the quality of DACPR using a simulation study.MethodsWe recruited laypersons at a shopping mall and measured the quality of CPR carried out in our simulation. Dispatchers provided instruction in accordance with the standard DACPR protocol in Japan.ResultsTwenty‐three laypersons (13 with CPR training experience within the past 2 years and 10 with no training experience) participated in this study. The median chest compression rate and depth were 106/min and 33 mm, respectively. The median time interval from placing the 119 call to the start of chest compressions was 119 s. No significant difference was found between the groups with and without training experience. However, subjects with training experience more frequently placed their hands correctly on the manikin (84.6% versus 40.0%; P = 0.026). Twelve participants (52.2%, seven in trained and five in untrained group) interrupted chest compressions for 3–18 s, because dispatchers asked if the patient started breathing or moving.ConclusionThis current simulation study showed that the quality of DACPR carried out by lay rescuers can be less than optimal in terms of depth, hand placement, and minimization of pauses. Further studies are required to explore better DACPR instruction methods to help lay rescuers perform CPR with optimal quality.
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