Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels mediate pacemaker currents in the atrium. The microRNA (miR) families miR-1 and miR-133 regulate the expression of multiple genes involved in myocardial function, including HCN channels. It was hypothesized that age-dependent changes in HCN2, HCN4, miR-1 and miR-133 expression may contribute to age-associated atrial fibrillation, and therefore the correlation between expression levels, among adult (≤65 years) and aged patients (≥65 years), and sinus rhythm was determined. Right atrial appendage samples were collected from 60 patients undergoing coronary artery bypass grafting. Reverse transcription-quantitative polymerase chain reaction (PCR) and western blot analyses were performed in order to determine target RNA and protein expression levels. Compared with aged patients with sinus rhythm, aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel mRNA and protein expression levels (P<0.05), but significantly lower expression levels of miR-1 and miR-133 (P<0.05). In addition, aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR-1 and -133 (P<0.05), compared with those of adult patients with sinus rhythm. Expression levels of HCN2 and HCN4 increased with age, and a greater increase was identified in patients with age-associated atrial fibrillation compared with that in those with aged sinus rhythm. These electrophysiological changes may contribute to the induction of ectopic premature beats that trigger atrial fibrillation.

Salidroside induces apoptosis in human ovarian cancer SKOV3 and A2780 cells through the p53 signaling pathway

“…Furthermore, p53 can influence apoptosis by regulating Bcl-2 (33). Previous studies have revealed that >50% of tumors are associated with p53 gene mutation; wild-type p53 gene therapy has been suggested to strengthen sensitivity to cisplatin in SKOV3 cells (34)(35)(36). In the present study, it was demonstrated that salidroside has the ability to induce OC apoptosis.…”

MicroRNA in cardiovascular biology and disease

“…Age-associated low levels of miR-1 and miR-133 contribute to the overexpression of HCN2 and HCN4, and this results in abnormal cardiac electrical activity. 42 …”

Heart Rate Control in Non-Paroxysmal Atrial Fibrillation. A New Indication for Ivabradine?

“…AF is a pathological condition in which ionic current remodeling has been demonstrated [14] . Regarding If current, an association between HCN overexpression in atrial and pulmonary vein cardiomyocytes and presence of AF has been reported in animal models and human [15][16][17][18] . In a canine model, He et al [17] demonstrated that mRNA and protein expression levels of HCN2 and HCN4 in the AF group were significantly increased when compared with the control group.…”

“…In a canine model, He et al [17] demonstrated that mRNA and protein expression levels of HCN2 and HCN4 in the AF group were significantly increased when compared with the control group. Li et al [18] analyzed right atrial appendage samples collected from 60 patients undergoing coronary artery bypass grafting; they observed that mRNA and protein expression levels of HCN2 and HCN4 channels in the right atrial appendage increased with age. Interestingly they also found that these age-associated expression modifications were even more pronounced in aged AF patients compared with aged sinus rhythm patients.…”