[Show abstract][Hide abstract] ABSTRACT: YKL-40, a proposed marker of inflammation and endothelial dysfunction, is associated with atherosclerosis and an increased cardiovascular mortality in the general population. However, the relationship between YKL-40 and arterial stiffness in hypertensive patients has not been adequately assessed.
The relationship between serum levels of YKL-40 and arterial stiffness was evaluated in 93 essential hypertensive subjects and 80 normal subjects. Essential hypertensive subjects were divided into two groups based upon urinary albumin-to-creatinine ratio (ACR): nonmicroalbuminuric group, (ACR <30 mg/g, n = 50) and microalbuminuric group (ACR ≥30 mg/g, n = 43). Large artery wall stiffness was assessed by measuring femoral arterial stiffness and carotid-femoral pulse wave velocity (cf-PWV). Serum levels of YKL-40 were determined by enzyme-linked immunosorbent assay (ELISA).
The study demonstrated that YKL-40,cf-PWV and femoral arterial stiffness were increased significantly (P<0.05) in the hypertensive group compared with normal controls. These measurements were also increased significantly ( P<0.05) in the microalbuminuric group compared with the nonmicroalbuminuric group. YKL-40 was positively correlated with cf-PWV( r = 0.44, P = 0.000) and femoral arterial stiffness ( r = 0.42, P =0.001). Multiple linear stepwise regression analysis showed that YKL-40 was the impact factor of arterial stiffness ( P<0.05).
YKL-40 levels are elevated in essential hypertension subjects with an independent association between increasing YKL-40 levels and increasing arterial stiffness. The study suggests it played a positive role of YKL-40 in the progressing vascular complications in patients with essential hypertension.
[Show abstract][Hide abstract] ABSTRACT: Molecular pathways involved in adventitial fibroblasts (AFs) and myofibroblasts (MFs) proliferation and apoptosis contribute to vascular remodeling. MicroRNA-21 (miR-21) plays an important role in regulating cellular proliferation and apoptosis of many cell types; however, the effect of miR-21 on AFs and MFs is still unknown. In this study, we found that miR-21 was expressed in AFs and overexpressed in MFs. Inhibition of miR-21 decreased proliferation and increased apoptosis of AFs and MFs, and overexpression of miR-21 with pre-miR-21 had the reverse effect. Programmed cell death 4 (PDCD4), related to cell proliferation and apoptosis, was validated as a direct target of miR-21 by dual-luciferase reporter assay and gain and loss of function of miR-21 in AFs and MFs. PDCD4 knockdown with siRNA partly rescued the reduced proliferation with miR-21 inhibition and alleviated the increased apoptosis induced by miR-21 inhibition in AFs and MFs. Moreover, increasing PDCD4 expression by miR-21 inhibition significantly decreased JNK/c-Jun activity. In contrast, decreasing PDCD4 expression by pre-miR-21 treatment increased JNK/c-Jun activity, while the effect of miR-21 inhibition on JNK/c-Jun activity could be rescued by PDCD4 siRNA. Moreover, miR-21 inhibition could regulate proliferation and apoptosis of vascular AFs and MFs in vivo. Furthermore, miR-21 inhibition reversed vascular remodeling induced by balloon injury. In summary, our findings demonstrate that miR-21 may have a critical role in regulating proliferation and apoptosis of AFs and MFs, and PDCD4 is a functional target gene involved in the miR-21-mediated cellular effects in vascular remodeling by a miR-21/PDCD4/JNK/c-Jun pathway.
Journal of Cellular Biochemistry 05/2012; 113(9):2989-3001. · 3.06 Impact Factor