Serum autoantibodies against human oxidized low-density lipoproteins are inversely associated with severity of coronary stenotic lesions calculated by Gensini score

Background: The relationship between autoantibodies against human oxidized low-density lipoprotein (anti-oxLDL) and the progression of atherosclerotic diseases is unclear. This study aimed to investigate the association between serum anti-oxLDL titers and the severity and extent of coronary stenotic lesions. Methods: We measured the titers of IgG anti-oxLDL by enzyme-linked immunosorbent assay (ELISA) in 154 consecutive patients undergoing coronary angiography for suspected coronary heart disease (CHD). The severity and extent of coronary stenotic lesions were evaluated on coronary angiography findings by Gensini score. Results: The anti-oxLDL titers were significantly lower in 117 patients with CHD than those in 37 controls (p < 0.01). The serum anti-oxLDL titers were significantly correlated to serum levels of globulin (r = 0.405), conjugated bilirubin (r = 0.280), high-density lipoprotein (HDL) cholesterol (r = 0.238), homeostatic model assessment for insulin resistance (HOMA-IR) (r = &#8211;0.267), high sensitivity C-reactive protein (hs-CRP) (r = &#8211;0.230), triglyceride (r = &#8211;0.207), advanced glycation end products (AGEs) (r = &#8211;0.200), and malondialdehyde (r = &#8211;0.165). However, only HDL cholesterol and AGEs remained independent predictors of the anti-oxLDL titers after adjusting for confounders. Multivariate regression analysis showed that the anti-oxLDL titers, as well as serum levels of hs-CRP, fasting glucose, and albumin, were significantly associated with Gensini scores. Conclusions: Titers of anti-oxLDL are inversely associated with complicated proatherogenic metabolic risk factors, and the severity of coronary stenotic lesions calculated by Gensini scores, supporting a protective role for anti-oxLDL against the progression of atherosclerosis. (Cardiol J 2011; 18, 4: 364&#8211;370

A novel three-dimensional and tissue Doppler echocardiographic index for diagnosing and prognosticating heart failure with preserved ejection fraction

Introduction: The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. In this study, a novel echocardiography index based on three-dimensional and tissue Doppler echocardiography for diagnosing and estimating prognosis in HFpEF. Materials and Methods: Patients with symptoms and/or signs of heart failure and normal left ventricular ejection fraction (LVEF ≥50%) who underwent right heart catheterization were screened. Patients were divided based on pulmonary capillary wedge pressure (PCWP) of ≥15 mmHg and PCWP <15 mmHg. A diagnosis of HFpEF was confirmed by PCWP of ≥15 mmHg according to ESC guidelines. A novel index was calculated by the ratio between stroke volume standardized to body surface area (SVI) and tissue Doppler mitral annulus systolic peak velocity S' (SVI/S'). Its diagnostic and prognostic values were determined. Results: A total of 104 patients (mean age 64 ± 12 years) were included. Of these, 63 had PCWP ≥15 mmHg and 41 patients had PCWP <15 mmHg. Compared to the PCWP <15 mmHg group, the ≥15 mmHg group had a significantly lower SVI/S' (P < 0.001). Logistic regression showed that SVI/S' was associated with high PCWP measured invasively. The SVI/S' had an area under the curve of 0.761 for diagnosing classifying between PCWP ≥15 mmHg and <15 mmHg. Kaplan–Meier analysis showed that the lower SVI/S' group showed a poorer prognosis. Conclusions: SVI/S' is a non-invasive index calculated by three-dimensional and tissue Doppler echocardiography. It is a surrogate measure of PCWP and can be used to diagnose and determine prognosis in HFpEF

Dietary Enterococcus faecium NCIMB 10415 and Zinc Oxide Stimulate Immune Reactions to Trivalent Influenza Vaccination in Pigs but Do Not Affect Virological Response upon Challenge Infection

Swine influenza viruses (SIV) regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy- two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high); 50 ppm, Zn(low)). Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high) and E. faecium groups gained weight after infection while those in the control group (Zn(low)) lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI) titers were also observed in the Zn(high)+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high) and E. faecium groups at single time points after infection compared to the Zn(low) control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology

A Novel Three-Dimensional and Tissue Doppler Echocardiographic Index for Diagnosing and Prognosticating Heart Failure With Preserved Ejection Fraction

INTRODUCTION: The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. In this study, a novel echocardiography index based on three-dimensional and tissue Doppler echocardiography for diagnosing and estimating prognosis in HFpEF. MATERIALS AND METHODS: Patients with symptoms and/or signs of heart failure and normal left ventricular ejection fraction (LVEF ≥50%) who underwent right heart catheterization were screened. Patients were divided based on pulmonary capillary wedge pressure (PCWP) of ≥15 mmHg and PCWP <15 mmHg. A diagnosis of HFpEF was confirmed by PCWP of ≥15 mmHg according to ESC guidelines. A novel index was calculated by the ratio between stroke volume standardized to body surface area (SVI) and tissue Doppler mitral annulus systolic peak velocity S' (SVI/S'). Its diagnostic and prognostic values were determined. RESULTS: A total of 104 patients (mean age 64 ± 12 years) were included. Of these, 63 had PCWP ≥15 mmHg and 41 patients had PCWP <15 mmHg. Compared to the PCWP <15 mmHg group, the ≥15 mmHg group had a significantly lower SVI/S' (P < 0.001). Logistic regression showed that SVI/S' was associated with high PCWP measured invasively. The SVI/S' had an area under the curve of 0.761 for diagnosing classifying between PCWP ≥15 mmHg and <15 mmHg. Kaplan–Meier analysis showed that the lower SVI/S' group showed a poorer prognosis. CONCLUSIONS: SVI/S' is a non-invasive index calculated by three-dimensional and tissue Doppler echocardiography. It is a surrogate measure of PCWP and can be used to diagnose and determine prognosis in HFpEF

Cardiopulmonary Bypass in Surgery for Interrupted Aortic Arch

Interrupted aortic arch is a complicated congenital heart defect. Because of its anatomic features, the conventional cardiopulmonary bypass (CPB) procedure is not suitable for the surgery of this type of lesion. Thus, we conducted a retrospective study of CPB in surgery for the disease. Ten patients with interrupted aortic arch underwent surgery by one of three different CPB methods, including profound hypothermia with circulatory arrest in four cases, profound hypothermia with low flow rate in five cases, and normothermia in one case. In profound hypothermic CPB, both ascending aorta and main pulmonary artery were cannulated. Through these two cannulas, the flow was pumped to the upper and lower body separately to cool down the body temperature. After cooling, the main pulmonary artery cannula was removed and interrupted aortic arch was corrected either under low flow rate perfusion or under circulatory arrest. After this, the other intracardiac lesions were repaired under conventional CPB. At the end of CPB, one patient demonstrated third-degree atria-ventricular block and required reinstituting CPB and a second procedure to repair the ventricular septal defect (VSD). In the intensive care unit, one patient developed lung infection and dyspnea after extubation that required intubation and mechanical ventilation for another several days. Another patient required 3 days of peritoneal dialysis caused by low cardiac output, hyperkalemia, and oliguria. All patients survived. The mechanical ventilation times were from 8 hours to 8 days and stays in the intensive care unit were from 4 to 12 days. Profound hypothermic cardiopulmonary bypass either with low flow rate or with circulatory arrest is equally the preferable choice for the surgery of interrupted aortic arch

Globular Adiponectin Attenuated H2O2-Induced Apoptosis in Rat Chondrocytes by Inducing Autophagy Through the AMPK/ mTOR Pathway

Background/Aims: Chondrocyte apoptosis is closely related to the development and progression of osteoarthritis. Global adiponectin (gAPN), secreted from adipose tissue, possesses potent anti-inflammatory and antiapoptotic properties in various cell types. This study aimed to investigate the role of autophagy induced by gAPN in the suppression of H2O2-induced apoptosis and the potential mechanism of gAPN-induced autophagy in chondrocytes. Methods: H2O2 was used to induce apoptotic injury in rat chondrocytes. CCK-8 assay was performed to determine the viability of cells treated with different concentrations of gAPN with or without H2O2. Cell apoptosis was detected by flow cytometry and TUNEL staining. Mitochondrial membrane potential was examined using JC-1 fluorescence staining assay. The autophagy inhibitors 3-MA and Bafilomycin A1 were used to treat cells and then evaluate the effect of gAPN-induced autophagy. To determine the downstream pathway, chondrocytes were preincubated with the AMPK inhibitor Compound C. Beclin-1, LC3B, P62 and apoptosis-related proteins were identified by Western blot analysis. Results: H2O2 (400 µM)-induced chondrocytes apoptosis and caspase-3 activation were attenuated by gAPN (0.5 µg/mL). gAPN increased Bcl-2 expression and decreased Bax expression. The loss of mitochondrial membrane potential induced by H2O2 was also abolished by gAPN. Furthermore, the antiapoptotic effect of gAPN was related to gAPN-induced autophagy by increased formation of Beclin-1 and LC3B and P62 degradation. In particular, the inhibition of gAPN-induced autophagy by 3-MA prevented the protective effect of gAPN on apoptosis induced by H2O2. Moreover, gAPN increased p-AMPK expression and decreased p-mTOR expression. Compound C partly suppressed the expression of autophagy-related proteins and restored the expression of p-mTOR suppressed by gAPN. Thus, the AMPK/mTOR pathway played an important role in the induction of autophagy and protection of H2O2-induced chondrocytes apoptosis by gAPN. Conclusions: gAPN protected chondrocytes from H2O2-induced apoptosis by inducing autophagy possibly associated with AMPK/mTOR signal-pathway activation

Periodic Mechanical Stress Stimulates the FAK Mitogenic Signal in Rat Chondrocytes Through ERK1/2 Activity

Background/Aims: The biological effects of periodic mechanical stress on chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying chondrocyte mechanosensing and signaling in response to periodic mechanical stress remain to be determined. In the current study, we examined the effects of focal adhesion kinase (FAK) signaling on periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. Methods and Results: Periodic mechanical stress significantly induced sustained phosphorylation of FAK at Tyr397 and Tyr576/577. Reduction of FAK with targeted shRNA via transfection of NH2-terminal tyrosine phosphorylation-deficient FAK mutant Y397F or Y576F-Y577F abolished periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis, accompanied by attenuated ERK1/2 phosphorylation. However, activation of Src, PLC&#947;1 and Rac1 was not prevented upon FAK suppression. Furthermore, pretreatment with the Src-selective inhibitor, PP2, and shRNA targeted to Src or suppression of Rac1 with its selective inhibitor, NSC23766, blocked FAK phosphorylation at Tyr,576/577 but not Tyr,397 under periodic mechanical stress. Interestingly, FAK phosphorylation neither at Tyr397 nor at Tyr576/577 was affected by PLC&#947;1 depletion when periodic mechanical stress was applied. In addition, Tyr397 and Tyr576/577 phosphorylation levels were reduced upon pretreatment with a blocking antibody against integrin β1 under conditions of periodic mechanical stress. Conclusion: Our findings collectively suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis through at least two pathways, integrin β1-Src-Rac1-FAK(Tyr576/577)-ERK1/2 and integrin β1-FAK (Tyr397)-ERK1/2

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

The mitogenic effects of periodic mechanical stress on chondrocytes have been studied extensively but the mechanisms whereby chondrocytes sense and respond to periodic mechanical stress remain a matter of debate. We explored the signal transduction pathways of chondrocyte proliferation and matrix synthesis under periodic mechanical stress. In particular, we sought to identify the role of the MEK1/2-ERK1/2 signaling pathway in chondrocyte proliferation and matrix synthesis following cyclic physiologic mechanical compression. Under periodic mechanical stress, both rat chondrocyte proliferation and matrix synthesis were significantly increased (P < 0.05) and were associated with increases in the phosphorylation of Src, PLCγ1, MEK1/2, and ERK1/2 (P < 0.05). Pretreatment with the MEK1/2-ERK1/2 selective inhibitor, PD98059, and shRNA targeted to ERK1/2 reduced periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis (P < 0.05), while the phosphorylation levels of Src-Tyr418 and PLCγ1-Tyr783 were not inhibited. Proliferation, matrix synthesis and phosphorylation of MEK1/2-Ser217/221 and ERK1/2-Thr202/Tyr204 were inhibited after pretreatment with the PLCγ1 inhibitor U73122 in chondrocytes in response to periodic mechanical stress (P < 0.05), while the phosphorylation site of Src-Tyr418 was not affected. Inhibition of Src activity with PP2 and shRNA targeted to Src abrogated chondrocyte proliferation and matrix synthesis (P < 0.05) and attenuated PLCγ1, MEK1/2 and ERK1/2 activation in chondrocytes subjected to periodic mechanical stress (P < 0.05). These findings suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis in part through the Src-PLCγ1-MEK1/2-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade