ABSTRACT
Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide.Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression.Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases.Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs.Thus,we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9,Tregs and CHF.Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients.Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA),we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ-Ⅲ group were lower than that in NYHA grade Ⅳ group.More importantly,the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF),whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF.The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF.Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.
ABSTRACT
Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide.Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression.Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases.Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs.Thus,we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9,Tregs and CHF.Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients.Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA),we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ-Ⅲ group were lower than that in NYHA grade Ⅳ group.More importantly,the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF),whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF.The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF.Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.
ABSTRACT
Osteoclast-like cells are known to inhibit arterial calcification. Receptor activator of NF-κB ligand (RANKL) is likely to act as an inducer of osteoclast-like cell differentiation. However, several studies have shown that RANKL promotes arterial calcification rather than inhibiting arterial calcification. The present study was conducted in order to investigate and elucidate this paradox. Firstly, RANKL was added into the media, and the monocyte precursor cells were cultured. Morphological observation and Tartrate resistant acid phosphatase (TRAP) staining were used to assess whether RANKL could induce the monocyte precursor cells to differentiate into osteoclast-like cells. During arterial calcification, in vivo and in vitro expression of RANKL and its inhibitor, osteoprotegerin (OPG), was detected by real-time PCR. The extent of osteoclast-like cell differentiation was also assessed. It was found RANKL could induce osteoclast-like cell differentiation. There was no in vivo or in vitro expression of osteoclast-like cells in the early stage of calcification. At that time, the ratio of RANKL to OPG was very low. In the late stage of calcification, a small amount of osteoclast-like cell expression coincided with a relatively high ratio of RANKL to OPG. According to the results, the ratio of RANKL to OPG was very low during most of the arterial calcification period. This made it possible for OPG to completely inhibit RANKL-induced osteoclast-like cell differentiation. This likely explains why RANKL had the ability to induce osteoclast-like cell differentiation but acted as a promoter of calcification instead.