Relationship between the Plasma Fibulin-1 Levels,Pulse Wave Velocity,and Vascular Age in Asymptomatic Hyperuricemia

Fibulin-1(FBLN-1),an elastin-associated extracellular matrix protein,has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease(CVD).We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity(baPWV)in patients with asymptomatic hyperuricemia(AHU).In total,66 patients with AHU and 66 gender-and age-matched healthy individuals were enrolled.The plasma fibulin-1 levels were measured by immunochemistry.Patients with AHU presented significantly higher vascular age[median(interquartile range):54(22)vs.48(14)years,P=0.01]and baPWV[mean±SD:1373±223 vs.1291±177 cm/s,P=0.02]than the healthy subjects;however,no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects[median(interquartile range):4018(3838)vs.3099(3405)ng/mL,P=0.31].A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU(r=0.29,P=0.02);and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age(r=0.22,P=0.08).However,these associations were rendered insignificant after adjustments for potential confounders.In healthy subjects,no correlation was observed between fibulin-1 levels and CVD risk.This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU,but the relationship is not robust.

Function of the CaMKII-ryanodine receptor signaling pathway in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia

BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.