Number of endothelial progenitor cells in peripheral artery disease as a marker of severity and association with pentraxin-3, malondialdehyde-modified low-density lipoprotein and membrane type-1 matrix metalloproteinase.

AIMS: Circulating endothelial progenitor cells (EPCs) were mobilized in cardiac ischemia, heart failure and vascular injuries associated with endothelial damage. Despite the occurrence of endothelial dysfunction in peripheral artery disease (PAD), few data are available on EPC mobilization in this setting. METHODS: We investigated the correlations between EPC and disease severity and also other biomarkers in PAD. EPCs assessed as CD34(+) cells co-expressing CD45(dim), CD133 and vascular endothelial growth factor receptor-2 were studied in PAD (n =48) and non-PAD (n =22) patients. Membrane type-1 matrix metalloproteinase (MT1-MMP) on peripheral blood mononuclear cells, serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) and plasma pentraxin-3 were also measured. RESULTS: The EPC level changed in the Fontaine and Trans-Atlantic Inter-Society Consensus (TASC) II classification. EPC was increased in Fontaine class IIa as compared with class IV and non-PAD patients (p < 0.05). EPCs and pentraxin-3 were increased in TASC II type A/B as compared with type C/D and non-PAD patients (p < 0.05), whereas the expression of MT1-MMP on peripheral blood mononuclear cells was significantly decreased in TASC II type A/B (both p < 0.05 versus type C/D and non-PAD patients). The EPC level showed a positive association with pentraxin-3 (r = 0.31; p < 0.05). There was an inverse association between the EPC level and MT1-MMP (r = -0.54; p < 0.01). The cardiovascular events was associated with reduced EPC and increased MDA-LDL (p < 0.05). CONCLUSION: EPC changed according to the Fontaine and TASC II classification and decreased in the advanced phases, and was associated with novel biomarkers and related to the severity of PAD.

Relationship between microcirculatory dysfunction and resolution of ST-segment elevation in the early phase after primary angioplasty in patients with ST-segment elevation myocardial infarction.

BACKGROUNDS AND OBJECTIVES: The aim of this study was to evaluate relationships between the degree of resolution of the ST-segment elevation (ST segment resolution; STR) and the extent of microcirculatory dysfunction in infarct-related area (IRA) in patients with ST-segment elevation myocardial infarction (STEMI) using (13)N-ammonia positron emission tomography (N-PET). METHODS: The subjects comprised 33 patients with STEMI who underwent successful reperfusion. Serial 12-lead electrocardiography (ECG) was performed at the baseline and at 100 min after reperfusion to calculate STR. The myocardial flow reserve (MFR) was assessed quantitatively using N-PET at 2 weeks after the onset. The summed defect score (SDS) of (99m)Tc-tetrofosmin myocardial perfusion imaging was used as an index of the severity of myocardial infarction. To assess the extent of post-infarct left ventricular remodeling, the changes in the LVEDVI (ΔEDVI) were also calculated. RESULTS: A significant correlation of the STR to the MFR in IRA (r = 0.68, p < 0.0001) was observed. A significant correlation was also identified between the SDS and the baseline sum ST-segment elevation (r = 0.65, p < 0.0001), while no correlation was observed between the SDS and the STR. Furthermore, a significant inverse correlation of the STR with the ΔEDVI was also recognized (r = -0.58, p < 0.01). CONCLUSIONS: These data indicate that STR after successful reperfusion in STEMI is closely related to the extent of microcirculatory disturbance; in other words, incomplete STR may be a marker of persistent microcirculatory dysfunction after reperfusion therapy.

Beneficial effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: Statin treatment has been shown to improve coronary endothelial function, irrespective of lipid-lowering effects. This study's aim was to elucidate the effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in acute myocardial infarction (AMI) patients. METHODS: Thirty-five patients undergoing successful reperfusion following AMI were assigned to a statin-treated (Group S, 16) or a non-statin-treated (Group NS, 19) group, according to fasting serum low-density lipoprotein-cholesterol. (13)N-ammonia positron emission tomography was performed to assess myocardial flow reserve (MFR) in the infarct area. RESULTS: Infarct sizes and lipid profiles during the chronic period were similar between the two groups. At 2 weeks after AMI onset, mean MFR in the infarct area was significantly higher in Group S than in Group NS (2.34 ± 0.63 vs. 1.91 ± 0.43, p=0.0214). At 6 months post-AMI, Group S had a smaller left-ventricular end-diastolic volume index (69.4 ± 11.7 mL/m(2) vs. 88.5 ± 32.5 mL/m(2), p=0.0328) and higher left-ventricular ejection fraction (67.7 ± 9.2% vs. 59.2 ± 13.3%, p=0.0394) than Group NS. Serum asymmetric dimethylarginine was significantly increased in Group NS at 1 month post-AMI (0.43 ± 0.12 µmol/L (baseline) vs. 0.52 ± 0.14 µmol/L, p=0.0186), but unchanged in Group S. CONCLUSIONS: Statin treatment appears to beneficially attenuate left ventricular remodeling after AMI, which may be associated with restoring coronary endothelial function via endogenous nitric oxide.

Acarbose treatments improve arterial stiffness in patients with type 2 diabetes mellitus.

UNLABELLED: Aims/Introduction: Although the improvement of postprandial hyperglycemia by an alpha-glucosidase inhibitor (α-GI) has been associated with a risk reduction of cardiovascular events, the relationship between postprandial hyperglycemia and arterial stiffness has not been well understood. We therefore examined whether ameliorating the postprandial state by α-GI leads to an improvement in arterial stiffness. MATERIALS AND METHODS: A total of 22 patients with type 2 diabetes mellitus were treated with acarbose. Cardio-ankle vascular index (CAVI) as the arterial stiffness was measured by using a VaSera CAVI instrument before and 12 months after acarbose treatment. Serum high-sensitivity C-reactive protein (hs-CRP), pentraxin-3 (PTX3) and matrix metalloproteinase (MMP) -2, -9 were measured at the same time points. Furthermore, circulating peripheral blood mononuclear cells were examined for the frequencies of CD14 positive cells expressing membrane type-1 MMP (MT1-MMP) at the single cell level using flow cytometry. RESULTS: After acarbose treatment, postprandial glucose and glycosylated hemoglobin (HbA1c) were significantly decreased. Serum levels of hs-CRP, PTX3, MMP-2 and MMP-9 were significantly decreased. CAVI showed a significant reduction, although the changes were not significant in blood pressure and heart rate. MT1-MMP expression was significantly decreased by acarbose treatment. In multivariate analysis, improvement of blood glucose, decrease of PTX3 levels and MT1-MMP expression were independent predictors of beneficial change in CAVI. CONCLUSIONS: The present study showed that the beneficial effects of acarbose on arterial stiffness are mediated by an improvement of postprandial hyperglycemia and vascular remodeling markers. In conclusion, acarbose treatment might reduce the risk of cardiovascular diseases by altering the arterial stiffness in postprandial hyperglycemic status. (J Diabetes Invest, doi:10.1111/j.2040-1124.2010.00079.x, 2010).