Relationship between sKL, BSP and HD abdominal aortic calcification and prognosis

Objective: To investigate the relationship between the expression levels of sKL and BSP and the calcification and prognosis of abdominal aorta in patients with HD. Methods: 130 patients with HD admitted to our hospital between January 2015 and June 2017 were selected as the research subjects;all patients were treated with Fresenius hemodialysis machine for intervention treatment;the expression levels of sKL and BSP in the patients' blood were monitored, and 30 mmonths were followed up The extent of calcification of the abdominal aorta and the quality of the prognosis of the patients were evaluated and the relationship between the expression levels of sKL and BSP and the calcification and prognosis of the abdominal aorta were analyzed. Results: The levels of sKL and BSP in the blood of patients with different degrees of abdominal aortic calcification were significantly different, and the differences were statistically significant (P <0.05). Among the patients with mild or no calcification, the levels of sKL and BSP were the highest in the blood and those in the death group were the lowest. The sKL level was significantly lower than the survival group, and the BSP level was significantly higher than the survival group, and the differences were statistically significant (P <0.05);the survival rate of patients with high sKL expression was significantly better than that of patients with low sKL expression, and the survival rate of low BSP expression was significantly better High expression in BSP;high sKL and low BSP are independent protective factors affecting abdominal aortic calcification and prognostic quality in HD patients (P <0.05);combined use of sKL and BSP in predicting the prognostic quality of HD patients is sensitive and specific Both are greater than 90%, and AUC> 0.90. Conclusions:High sKL and low BSP in the blood of HD patients are independent protective factors affecting abdominal aortic calcification and prognostic quality. The combined application of sKL and BSP can effectively predict the prognostic quality value of patients.

A novel mouse model of calcific aortic valve stenosis

Background:Calcific aortic valve stenosis(CAVS)is one of the most challenging heart diseases in clinical with rapidly increasing prevalence.However,study of the mecha-nism and treatment of CAVS is hampered by the lack of suitable,robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposi-tion.Here,we aim to establish a mouse model to mimic the development and features of CAVS.Methods:The model was established via aortic valve wire injury(AVWI)combined with vitamin D subcutaneous injected in wild type C57/BL6 mice.Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradi-ent.Histopathological specimens were collected and examined in respect of valve thickening,calcium deposition,collagen accumulation,osteogenic differentiation and inflammation.Results:Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time depend-ent manner and tended to be stable at 28 days.Compared with the sham group,sim-ple AVWI or the vitamin D group,the hybrid model group showed typical pathological features of CAVS,including hemodynamic alterations,increased aortic valve thicken-ing,calcium deposition,collagen accumulation at 28 days.In addition,osteogenic dif-ferentiation,fibrosis and inflammation,which play critical roles in the development of CAVS,were observed in the hybrid model.Conclusions:We established a novel mouse model of CAVS that could be induced efficiently,robustly and economically,and without genetic intervention.It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effec-tive pharmacological targets.

Effects of Atorvastatin on Warfarin-induced Aortic Medial Calcification and Systolic Blood Pressure in Rats

The effect of atorvastatin on warfarin-induced aortic medial calcification and systolic blood pressure （SBP） of rats induced by warfarin was studied. Thirty healthy and adult rats were randomly divided into Warfarin group （n=10）, Atorvastatin group （n=10） and normal control group （n=10）. Caudal arterial pressure of rats was measured once a week, and 4 weeks later, aorta was obtained. Elastic fiber, collagen fiber and calcium accumulation in tunica media of cells were measured by Von Kossa staining. The results showed that warfarin treatment led to elevation of systolic blood pressure and aortic medial calcification. The chronic treatment also increased collagen, but decreased elastin in the aorta. However, the atorvastatin treatment had adverse effects. It was concluded that treatment with atorvastatin presented evidence of blood pressure lowing and calcification reducing. These data demonstrate that atorvastatin protected aortic media from warfarin-induced calcification and elevation of systolic blood pressure.

Role of Wnt/β-catenin Signaling Pathway in the Mechanism of Calcification of Aortic Valve

Aortic valve calcification is a common disease in the elderly, but its cellular and molecular mechanisms are not clear. In order to verify the hypothesis that Wnt/β-catenin signaling pathway is involved in the process of calcification of aortic valve, porcine aortic valve interstitial cells（VICs） were isolated, cultured and stimulated with oxidized low density lipoprotein（ox-LDL） for 48 h to induce the differentiation of VICs into osteoblast-like cells. The key proteins and genes of Wnt/β-catenin signaling pathway, such as glycogen synthase kinase 3β（GSK-3β） and β-catenin, were detected by using Western blotting and real-time polymerase chain reaction（PCR）. The results showed that the VICs managed to differentiate into osteoblast-like cells after the stimulation with ox-LDL and the levels of proteins and genes of GSK-3β and β-catenin were increased significantly in VICs after stimulation for 48 h（P0.05）. It is suggested that Wnt/β-catenin signaling pathway may play a key role in the differentiation of VICs into osteoblast-like cells and make great contribution to aortic valve calcification.

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

Effects of Lanthanum Carbonate on Vascular Calcification in Elderly Maintenance Hemodialysis Patients

Summary： The effect of lanthanum carbonate on abdominal aortic calcification （AAC） in the elderly maintenance hemodialysis （MHD） patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group （n=28） and control group （n=26）. The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone （iPTH） levels and AAC scores at third month after treatments were compared be- tween the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen （BUN）, serum creatinine （Scr）, uric acid, albumin, hemoglobin, C reactive protein （CRP）, low density lipoprotein （LDL）, high density lipoprotein （HDL）, triglyceride, total cholesterol between case group and control group （P〉0.05 for all）. There was also no significant difference in the baseline itching scores between the case group and the control group （P〉0.05）. At 1st and 3rd month after treatment, the itching scores in the case group were 14.2±3.2 and 10.5±2.3, respectively, which were significantly lower than the baseline and those in the control group （P〈0.05 for all）. At 1 st and 3rd month after treatment, the itching scores in the control group were 23.6v5.9 and 24.8±6.3, respectively, which were significantly higher than the baseline （P〈0.05）. There was no significant difference in the baseline of serum calcium, phos- phorus, calcium-phosphorus products, iPTH levels between the case group and control group （P〉0.05）. At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline （P〈0.05）, and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group （P〈0.05）. The AAC scores showed statistically significant difference between the case group and the control group （P〈0.05）. The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbon- ate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phos- phorus and iPTH levels, resulting in the attenuation of vascular calcification.

Role of different imaging modalities of vascular calcification in predicting outcomes in chronic kidney disease

Vascular calcification(VC) is common among patientswith chronic kidney disease(CKD).The severity of VC is associated with increased risk of cardiovascular events and mortality.Risk factors for VC include traditional cardiovascular risk factors as well as CKD-related risk factors such as increased calcium and phosphate load.VC is observed in arteries of all sizes from small arterioles to aorta,both in the intima and the media of arterial wall.Several imaging techniques have been utilized in the evaluation of the extent and the severity of VC.Plain radiographs are simple and readily available but with the limitation of decreased sensitivity and subjective and semi-quantitative quantification methods.Mammography,especially useful among women,offers a unique way to study breast arterial calcification,which is largely a medial-type calcification.Ultrasonography is suitable for calcification in superficial arteries.Analyses of wall thickness and lumen size are also possible.Computed tomography(CT) scan,the gold standard,is the most sensitive technique for evaluation of VC.CT scan of coronary artery calcification is not only useful for cardiovascular risk stratification but also offers an accurate and an objective analysis of the severity and progression.

Aβ40 Promotes the Osteoblastic Differentiation of Aortic Valve Interstitial Cells through the RAGE Pathway

Amyloid beta(AB)peptide 40 enhances the activation of receptor for advanced glycation end products(RAGE)in immune-inflammatory diseases.RAGE exhibits several ffects in the setting of numerous cardiovascular events.We bypothesized that the Aβ40/RAGE pathway is involved in the osteoblastic differentiation of the valvular interstitial cell(VIC)phenotype,and RAGE knockout intervention could reduce the calcification of aortic valve interstitial cells(AVICs)by inhibiting the extracellular-regulated kinase1/2(ERK 1/2)/nuclear factor kappa-B(NF-kB)signaling pathway.To test this hypothesis,the activation of AB40/RAGE pathway in human calcific AVs was evaluated with immunohistochemical staining.Cultured calcific VIC models were used in vitro.The VICs were stimulated using Aβ40,with or without RAGE small interfering ribonucleic acid(siRNA),and ERK1/2 and NF-κB inhibitors for analysis.Our data revealed that AB40 induced the ERK 1/2/NF-κB signaling pathway and osteoblastic differentiation of AVICs via the RAGE pathway in vitro.

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）.

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.