Upregulation of Cartilage Oligomeric Matrix Protein and Bone Morphogenetic Protein-2 May Associate with Calcific Aortic Valve Disease

Objective:Calcific aortic valve disease(CAVD)affects millions of elderly people,and there is currently no effective way to stop or slow down its progression.Therefore,exploring the pathogenesis of CAVD is very important for prevention and treatment.Cartilage oligomeric matrix protein(COMP)have important role in cell phenotype change.This study is aimed to confirm whether COMP participate in CAVD and try to find the possible mechanisms.Methods:Human aortic valve tissues from Nanjing First Hospital(CAVD group,n=20;control group,n=11)were harvested.The expression level of COMP was tested by western blot and immunohistochemistry.Dual immunofluorescence staining was used for locating COMP.Bone morphogenetic protein-2(BMP2)signalling were tested by western blot.The animal model was also used to detect COMP level by immunohistochemistry.Results:The results showed that the expression level of COMP was significantly increased in the calcific valve samples when compared with that of the control valve(P<0.05);COMP was expressed near the calcific nodules and co-localized with a-smooth muscle actin(a-SMA).The protein levels of BMP2 and p-Smads 1/5/9 were markedly more highly expressed in the CAVD group than the control group(P<0.05).Furthermore,immunofluorescence detection showed that COMP and BMP2 were co-located in calcific valves.Conclusions:The above results suggested that upregulation of COMP and BMP2 may be associated with aortic valve calcification and that COMP may become a potential therapeutic target in human CAVD.

The Characterization of Aortic Valve Calcification at Different Stage of Disease

Cardiac valve calcification is a common disease,especially among the elderly.Calcification can affect valve function and cause heart failure and sudden death(Adler et al.,2002).Aortic valve calcification is alsorelated to arteriosclerosis and coronary heart disease(Rashedi et al.,2015).However,the origin of valve calcification is still unclear.This study characterized the

Oxidized phospholipids and lipoprotein-associated phospholipase A_2 as important determinants of Lp(a) functionality and pathophysiological role

Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.