Fumiyoshi Tsunoda

Elevation of matrix metalloproteinases and interleukin‐6 in the culprit coronary artery of myocardial infarction

Background  Interleukin‐6 (IL‐6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI.

Postprandial changes in LDL phenotypes in patients with myocardial infarction

Background  Low‐density lipoprotein (LDL) particle size is strongly affected by both fasting and postprandial triglyceride levels. We report here that the LDL phenotype shifts toward the smaller phenotype during oral fat tolerance tests (OFTTs) in some patients with myocardial infarction (MI); a condition closely associated with postprandial increases of triglyceride and remnant‐like particles (RLPs).

Beneficial Effects of Exercise-Based Cardiac Rehabilitation on High-Density Lipoprotein-Mediated Cholesterol Efflux Capacity in Patients with Acute Coronary Syndrome

AIM Recent studies reported that low high-density lipoprotein (HDL)-mediated cholesterol efflux capacity rather than low HDL cholesterol (HDL-C) is strongly associated with the increased risk for coronary artery disease. It remains unclear whether exercised-based cardiac rehabilitation (CR) can increase HDL cholesterol efflux capacity. METHOD This study is a retrospective analysis of stored serum from patients with acute coronary syndrome (ACS) who participated in outpatient CR program following successful percutaneous coronary intervention. We employed a cell-based cholesterol efflux system including the incubation of (3)H-cholesterol labeled macrophages with apolipoprotein B-depleted serum at the onset or early phase of ACS and at 6-month follow-up periods in 57 male and 11 female patients with ACS. Cardiopulmonary exercise tests were performed at the beginning and end of CR program. RESULT Fifty-seven patients completed the CR program. Compared with patients who dropped out from CR program (non-CR group), CR participants showed marked amelioration in serum lipid levels, increased efflux capacity, and improved exercise capacity. Spearmans rank correlation coefficient analysis revealed that the percent increases of efflux capacity were significantly associated with the percent increases in HDL-C (ρ=0.598, p＜0.0001) and apolipoprotein A1 (ρ=0.508, p＜0.0001), whereas no association between increases in efflux capacity and increases in cardiopulmonary fitness was observed. Increases in cholesterol efflux capacity were not seen in patients who continued smoking and those who did not achieve all risk factor targets and higher exercise tolerance. CONCLUSION CR can markedly increase both HDL-C and HDL cholesterol efflux capacity. These results suggest that CR is a very useful therapy for reverse cholesterol transport and secondary prevention.

Effects of Cardiac Rehabilitation on High-Density Lipoprotein-mediated Cholesterol Efflux Capacity and Paraoxonase-1 Activity in Patients with Acute Coronary Syndrome

Aims: We evaluated whether exercised-based cardiac rehabilitation (CR) can ameliorate the HDL function, i.e., cholesterol efflux capacity (CEC) and paraoxonase-1 activity in patients with acute coronary syndrome (ACS). Methods: This study is a retrospective analysis of stored serum from patients with ACS following successful percutaneous coronary intervention. The CEC, measured by a cell-based ex vivo assay using apolipoprotein B-depleted serum and 3H-cholesterol labeled macrophages and arylesterase activity (AREA) at the onset or early phase of ACS, and the follow-up periods were compared between 69 patients who completed the five-month outpatient CR program (CR group) and 15 patients who did not participate and/or dropped out from CR program (non-CR group). Results: Apolipoprotein A-I (apoA-I) and CEC significantly increased by 4.0% and 9.4%, respectively, in the CR group, whereas HDL-cholesterol and AREA were not changed during the follow-up periods in both groups. Among CR patients, the CEC significantly increased, irrespective of the different statin treatment, while HDL-cholesterol and apoA-I significantly increased in patients treated with rosuvastatin or pitavastatin. Although CEC and AREA were significantly correlated each other, there is a discordance between CEC and AREA for their correlations with other biomarkers. Both CEC and AREA were significantly correlated with apoA-I rather than HDL-cholesterol. Changes in CEC and those in AREA were significantly correlated with those in apoA-I (rho = 0.328, p = 0.002, and rho = 0.428, p < 0.0001, respectively) greater than those in HDL-cholesterol (rho = 0.312, p = 0.0042, and rho = 0.343, p = 0.003, respectively). Conclusions: CR can improve HDL function, and it is beneficial for secondary prevention.

Therapeutic potential of cycling high-intensity interval training in patients with peripheral artery disease: A pilot study

a Showa University Research Institute for Sport and Exercise Sciences, Yokohama, Japan b Division of Cardiology, Showa University Fujigaoka Rehabilitation Hospital, Yokohama, Japan c Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan d Cardiac Rehabilitation, Showa University Fujigaoka Rehabilitation Hospital, Yokohama, Japan e Department of Physical Therapy, School of Health Sciences, Tokyo University of Technology, Tokyo, Japan

Small dense low-density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease: sdLDL for secondary prevention in men

The study objective was to investigate whether small dense low‐density lipoprotein cholesterol (sdLDL‐C) is superior to low‐density lipoprotein cholesterol (LDL‐C) and other biomarkers to predict future cardiovascular events (CE) in secondary prevention.

AMELIORATION OF CHOLESTEROL EFFLUX CAPACITY BY CARDIAC REHABILITATION IN PATIENTS WITH ACUTE CORONARY SYNDROME

It has been reported that exercised-based cardiac rehabilitation (CR) can increase HDL-C in patients with coronary artery disease (CAD). However it remains unclear how CR ameliorate HDL function. We measured cholesterol efflux capacity (CEC) in 30 patients with acute coronary syndrome (ACS) and 17

Comparison Between Small Dense LDL-Cholesterol and LDL-Cholesterol to Predict Coronary Events in Stable Coronary Heart Disease

Recent evidence suggests that small dense low-density lipoprotein (sd-LDL) particles are more atherogenic than large-LDLs in spite of their lower cholesterol contents. This study aimed to determine whether sd-LDL-cholesterol (sd-LDL-C) is superior to LDL-C as a biomarker of the severe coronary heart disease (CHD). We compared the LDL particle size by gradient gel electrophoresis and sd-LDL-C concentrations quantified by heparin-magnesium precipitation in two groups: 482 consecutive patients with stable CHD who had undergone coronary arteriography and 389 non-diabetic subjects without CHD who were not receiving any lipid-lowering drugs. The LDL size, large-LDL-C (estimated by subtracting the sd-LDL-C concentration from the LDL-C concentration), and HDL-C were significantly lower in the CHD subjects than in the healthy subjects, and the sd-LDL-C was significantly higher, in both men and women. The LDL-C was modestly higher and the sd-LDL-C was significantly higher in 258 patients with coronary events (defined as coronary revascularization therapy) than in the patients without events, irrespective of treatment by LDL-lowering drugs. Large-LDL-C, in contrast, was similar between the two groups. Multivariate logistic regression analysis revealed that sd-LDL-C levels were significantly associated with coronary events independently of LDL-C, HDL-C, and high-sensitivity CRP. The sd-LDL-C levels are more powerful than LDL-C levels as disease markers for the determination of high-risk patients among patients with stable CHD.

Significance of Small Dense Low-Density Lipoproteins in Coronary Heart Disease

Low-density lipoprotein (LDL) particles are heterogeneous with respect to their size, density, and lipid composition, and the size of LDL particles is chiefly determined by their lipid contents. Small dense LDL particles have been suggested to be highly atherogenic compared to large buoyant LDL. Our case-control studies have shown that the LDL particle size determined by gradient gel electrophoresis was remarkably smaller in patients with coronary heart disease (CHD), irrespective of the presence of diabetes and the differences in clinical situation and severity of CHD. In addition, small dense LDL-cholesterol concentration evaluated by heparin magnesium precipitation was significantly higher in severe stable CHD and acute coronary syndrome compared with non-CHD subjects and patients with mild CHD, while large LDL-cholesterol estimated by subtracting the small dense LDL-cholesterol concentration from the LDLcholesterol concentration, were somewhat lower in stable CHD compared with healthy subjects. Furthermore, reduced LDL particle size and elevated small dense LDL-cholesterol levels were significantly associated with metabolic dyslipidemia in Metabolic syndrome. These suggest that the predominance of small dense LDL and high levels of small dense LDLcholesterol are very promising risk marker for CHD.

Cardioprotective effect of G-CSF administration after coronary reperfusion in swine AMI model

[Purpose] Recent studies have suggested that granulocyte colony-stimulating factor (G-CSF) may accelerate angiogenesis or cardio-myogenesis. No previous studies, however, have used large animal models to investigete how clinical doses of G-CSF affect cardiac function after acute myocardial infarction (AMI). [Methods] Diagonal branch of the left anterior descending coronary artery of domestic swine was balloon-occluded for 1-hour and then reperfused. The G-CSF group received a subcutaneous injection of G-CSF at a dose of 5.0/µg/kg/day for 6 days after MI. Left ventriculography was performed 4 weeks after Ml. The number of vessels in the infarcted area were calculated using sections stained by anti-α-smooth muscle actin (SMA) and anti-von Willebrand factor (vWF). Reverse transcription polymerase chain reactions for collagen I, collagen III, and transforming growth factor (TGF)-β were also examined. [Results] The G-CSF group showed a significantly higher ejection fraction and lower end-diastolic volume in left ventriculography. The numbers of α-SMA- and vWF-positive vessels in the G-CSF group were significantly larger. The expression of collagen III mRNA was significantly lower in the G-CSF group in the infarct and border areas. The expression of TGF-β mRNA was significantly lower in the G-CSF group in the border area. [Conclusions] The administration of clinical doses of G-CSF improved cardiac function after reperfusion in AMI. G-CSF confers its effects by accelerating angio-genesis and modifying the wound-healing process.