Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) expressing monocytes in individuals with type 2 diabetes mellitus.

BACKGROUND: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16-, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD. METHODS: Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers. RESULTS: Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM. CONCLUSIONS: Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.

The relationship between terminal QRS distortion on initial ECG and final infarct size at 4months in conventional ST- segment elevation myocardial infarct patients.

BACKGROUND: In the Sclarovsky-Birnbaum Ischemia Severity Grading System for patients with ST-segment elevation myocardial infarction (STEMI), "Terminal QRS distortion" is considered as "Grade III". This evidence for most severe ischemia is associated with cardiovascular magnetic resonance imaging (CMR) markers of myocardial damage in the subacute phase. Our aim was to assess whether terminal QRS distortions on the initial electrocardiogram (ECG) is predictive for infarct size (IS) and left ventricular ejection fraction (LVEF) at 4months in anterior versus infarct locations. METHODS: Patient data of the HEBE, GIPS III and MAST, were pooled. ECGs of 411 STEMI patients were classified as absence (Grade II) or presence (Grade III) of terminal QRS distortion according to Sclarovsky-Birnbaum grading. CMR was performed at approximately 4months and included IS and LVEF. RESULTS: Grade III ischemia was present in 142 of 411 (35%) patients and was more frequently observed with inferior STEMI (P=0.01). In the total cohort and in anterior STEMI, no difference in LVEF or IS was observed between the two Grades. Whereas, in inferior STEMI Grade III was associated with a larger IS (P<0.01) and also, a trend towards a lower LVEF was observed (P=0.09). CONCLUSION: In inferior STEMI, terminal QRS distortion on the initial ECG is associated with a larger IS at approximately 4months, and can be used to identify a high-risk population in the acute phase. Also, a Grade III was associated with a trend towards a lower LVEF.

Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers.

AIMS/HYPOTHESIS: Individuals with type 2 diabetes mellitus have increased rates of macrovascular disease (MVD). Endothelial progenitor cells (EPCs), circulating angiogenic cells (CACs) and smooth muscle progenitor cells (SMPCs) are suggested to play a role in the pathogenesis of MVD. The relationship between vasoregenerative EPCs or CACs and damaging SMPCs and the development of accelerated MVD in diabetes is still unknown. We tried to elucidate whether EPC, CAC and SMPC numbers and differentiation capacities in vitro differ in patients with and without diabetes or MVD. METHODS: Peripheral blood was obtained from individuals with and without diabetes and MVD (coronary or peripheral artery disease). EPC and SMPC numbers were determined with flow cytometry. Furthermore, CAC and SMPC numbers were quantified after in vitro culture. Their in vitro differentiation capacity was investigated with real-time RT-PCR and quantitative immunofluorescence. RESULTS: In diabetic patients both EPC and CAC levels were reduced (1.3-fold [p < 0.05] and 1.5-fold [p < 0.05], respectively). CAC outgrowth from diabetic patients with MVD was reduced 1.5-fold compared with diabetic patients without MVD (p < 0.05). SMPC levels were similar between diabetic patients and healthy controls. The CAC/SMPC ratio of in vitro cultured progenitor cells was reduced 2.3-fold in samples from diabetic patients (p < 0.001). The differentiation capacity of CACs and SMPCs in vitro remained similar independently of diabetes or MVD. CONCLUSIONS/INTERPRETATION: The ratio between EPCs or CACs and SMPCs is disturbed in type 2 diabetes in favour of SMPCs. This may translate into reduced vascular repair capacity, thereby promoting MVD in type 2 diabetes.

Cardiac magnetic resonance imaging in daily practice in a peripheral medical centre: description of the first 383 patients.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging has evolved over the last decade into an indispensable diagnostic instrument. CMR imaging noninvasively provides structural, functional and morphological information with high spatial resolution and an unlimited field of view. Since October 2006 the VieCuri Medical Centre in Venlo has a CMR scanner at its disposal. OBJECTIVES: The goal of this study was to analyse the impact of CMR imaging on diagnosis and treatment in daily practice in the setting of a medium-volume peripheral hospital. METHODS: All patients who underwent CMR imaging between October 2006 and November 2008 were included in this analysis. The medical history before and after the CMR scan, the application form for CMR imaging and the outcome of the scans were reviewed. CMR images, obtained using a 1.5-T magnetic resonance imaging system, were reviewed by a multidisciplinary team. RESULTS: In 235 patients CMR imaging demonstrated one or more abnormalities, whereas CMR imaging did not identify any abnormalities in 148 patients. CMR imaging confirmed an expected finding in 166 cases, identified an unexpected condition in 69 cases, ruled out an expected finding in 59 cases and ruled out a suspected condition in 89 cases. Due to better insight into diagnosis, CMR imaging resulted in a change of treatment in 166 of the total of 383 CMR scans (43%). CONCLUSION: In a relevant number of cases CMR imaging leads to a change in the treatment of a patient, proving the value of CMR imaging as a diagnostic modality. Therefore, CMR imaging is an excellent opportunity for peripheral medical centres to improve efficiency and the standard of patient care. (Neth Heart J 2010;18:524-30.).