Yasuto Hoshino

Serum tenascin-C level is associated with coronary plaque rupture in patients with acute coronary syndrome

Tenascin-C, a large oligometric glycoprotein of the extracellular matrix, increases the expression of matrix metalloproteinases that lead to plaque instability and rupture, resulting in acute coronary syndrome (ACS). We hypothesized that a high serum tenascin-C level is associated with plaque rupture in patients with ACS. Fifty-two consecutive ACS patients who underwent emergency percutaneous coronary intervention (PCI) and, as a control, 66 consecutive patients with stable angina pectoris (SAP) were enrolled in this study. Blood samples were obtained from the ascending aorta just prior to the PCI procedures. After coronary guide-wire crossing, intravascular ultrasonography (IVUS) was performed for assessment of plaque characterization. Based on the IVUS findings, ACS patients were assigned to two groups according to whether there was ruptured plaque (ruptured ACS group) or not (nonruptured ACS group). There were 23 patients in the ruptured group and 29 patients in the nonruptured group. Clinical characteristics and IVUS measurements did not differ between the two groups. Tenascin-C levels were significantly higher in the ruptured ACS group than in the SAP group, whereas there was no significant difference between the nonruptured ACS and SAP groups. Importantly, in the ruptured ACS group, tenascin-C levels were significantly higher than in the nonruptured ACS group (71.9 ± 34.9 vs 50.5 ± 20.5 ng/ml, P < 0.005). Our data demonstrate that tenascin-C level is associated with pathologic conditions in ACS, especially the presence of ruptured plaque.

Peripheral blood progenitor cell collection by two programs for autologous and allogeneic transplantation

In the Spectra apheresis instrument (Terumo BCT), both manual (Spectra‐MNC) and automated (Spectra‐Auto) programs have been widely used to collect peripheral blood progenitor cells (PBPCs). However, direct comparison of these programs remains extremely limited.

Intravascular ultrasound predictors of acute side branch occlusion in coronary artery bifurcation lesions just after single stent crossover.

We aimed to assess the intravascular ultrasound (IVUS) predictors of acute side branch (SB) occlusions just after single stent crossover in percutaneous coronary intervention (PCI) for coronary bifurcation lesions.

Coronary Artery Spasm Related to Thiol Oxidation and Senescence Marker Protein-30 in Aging

BACKGROUND Senescence marker protein-30 (SMP30) decreases with aging, and SMP30 knockout (KO) mice show a short life with increased oxidant stress. AIMS We assessed the effect of oxidant stress with SMP30 deficiency in coronary artery spasm and clarify its underlying mechanisms. RESULTS We measured vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) of isolated coronary arteries from SMP30 KO and wild-type (WT) mice. In SMP30 KO mice, ACh-induced vasoconstriction occurred, which was changed to vasodilation by dithiothreitol (DTT), a thiol-reducing agent. However, Nω-nitro-L-arginine-methyl ester, nitric oxide (NO) synthase inhibitor, or tetrahydrobiopterin did not change the ACh response. In isolated coronary arteries of WT mice, ACh-induced vasodilation occurred. Inhibition of glutathione reductase by 1, 3-bis(2-chloroethyl)-1-nitrosourea decreased ACh-induced vasodilation (n=10, p<0.01), which was restored by DTT. To evaluate the thiol oxidation, we measured the fluorescence of monochlorobimane (MCB) in coronary arteries, which covalently labels the total. The fluorescence level to MCB decreased in SMP30 KO mice, but with DTT treatment restored to a level comparable to that of WT mice. The reduced glutathione and total thiol levels were also low in the aorta of SMP30 KO mice compared with those of WT mice. Administration of ACh into the aortic sinus in vivo of SMP30 KO mice induced coronary artery spasm. INNOVATION The thiol redox state is a key regulator of endothelial NO synthase activity, and thiol oxidation was associated with endothelial dysfunction in the SMP30 deficiency model. CONCLUSION These results suggest that chronic thiol oxidation by oxidant stress is a trigger of coronary artery spasm, resulting in impaired endothelium-dependent vasodilation.

Age-related oxidant stress with senescence marker protein-30 deficiency plays a pivotal role in coronary artery spasm.

ObjectivesWe examined the mechanism of coronary artery spasm related to oxidant stress with aging in senescence marker protein-30 (SMP30)-deficient mice because SMP30 decreases with aging and SMP30 knockout (KO) mice show a short life with increased oxidant stress. MethodsTo examine the effect of SMP30 on coronary artery vasomotor tone, we measured the endothelium-dependent [5-hydroxytryptamine (5-HT)] response of isolated, pressurized coronary arteries from SMP30 KO and wild-type (WT) mice (n=10 each). ResultsIn SMP30 KO mice, 5-HT-induced vasoconstriction occurred, which altered vasodilation with dithiothreitol, a thiol-reducing agent. In WT mice, 5-HT-induced vasodilation occurred. Administration of 5-HT from the aortic sinus induced a coronary artery spasm in SMP30 KO mice, which was prevented by the intravenous administration of Y-27632, rho-kinase inhibitor. The fluorescence level of monochlorobimane in coronary arteries, which covalently labels the reduced total thiols, decreased in SMP30 KO mice, but reverted to a level comparable with that of WT mice on treatment with Y-27632. From these results, SMP30 provides protection against coronary artery spasm. ConclusionChronic oxidant stress associated with aging plays an important role in coronary artery spasm related to thiol oxidation and rho-kinase signaling.

ELEVATED SOLUBLE LECTIN-LIKE OXIDIZED LDL RECEPTOR-1 (LOX-1) IN CORONARY CIRCULATION OF PATIENTS WITH ACUTE CORONARY SYNDROME

Results: Soluble LOX-1 levels in Ao and CS were signiicantly higher in ACS than in EAP (P<0.0001, each). We found the positive correlation between Ao and CS LOX-1 values in ACS (R=0.676, P<0.0001), but not in EAP, suggesting that elevated LOX-1 was derived from coronary cir culation. The LOX1 values increased earlier after the onset compared to other markers for ACS such as CK-MB and troponin I. Correlations between LOX-1 and CK-MB, troponin I or CRP were not observed in ACS. Conclusions: This study showed that soluble LOX-1 levels in coronary circulation were elevated in ACS, suggesting that soluble LOX-1 is a speciic biomarker of vulnerable plaque in ACS.