Acute kidney injury induces the loss of renal microvessels, but the fate of endothelial cells and the mechanism of potential vascular endothelial growth factor (VEGF)-mediated protection is unknown. Cumulative cell proliferation was analyzed in the kidney of Sprague-Dawley rats following ischemia-reperfusion (I/R) injury by repetitive administration of BrdU (twice daily) and colocalization in endothelial cells with CD31 or cablin. Proliferating endothelial cells were undetectable for up to 2 days following I/R and accounted for only ∼1% of BrdU-positive cells after 7 days. VEGF-121 preserved vascular loss following I/R but did not affect proliferation of endothelial, perivascular cells or tubular cells. Endothelial mesenchymal transition states were identified by localizing endothelial markers (CD31, cablin, or infused tomato lectin) with the fibroblast marker S100A4. Such structures were prominent within 6 h and sustained for at least 7 days following I/R. A Tie-2-cre transgenic crossed with a yellow fluorescent protein (YFP) reporter mouse was used to trace the fate of endothelial cells and demonstrated interstititial expansion of YFP-positive cells colocalizing with S100A4 and smooth muscle actin following I/R. The interstitial expansion of YFP cells was attenuated by VEGF-121. Multiphoton imaging of transgenic mice revealed the alteration of YFP-positive vascular cells associated with blood vessels characterized by limited perfusion in vivo. Taken together, these data indicate that vascular dropout post-AKI results from endothelial phenotypic transition combined with an impaired regenerative capacity, which may contribute to progressive chronic kidney disease.

ObjectiveTo explore the clinical and neuroendocrine characteristics of syndromes of orthostatic intolerance and syncope in young adults.MethodsTwo hundred and thirty-six patients aged 18–40 years with orthostatic intolerance and/or syncope were examined by head-up tilt test (HUT). Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1 and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were analysed. Patients’ history, haemodynamic parameters and plasma biomarkers were related to main diagnoses such as vasovagal syncope (VVS), postural tachycardia syndrome (POTS), orthostatic hypotension (OH) and negative HUT.ResultsNo self-reported symptom of orthostatic intolerance was highly specific for any diagnosis. Patients with VVS (n=103) were more likely to be men (p=0.011) and had lower resting heart rate (HR; 66±11) compared with POTS (73±11; n=72; p=0.001) and negative HUT (74±11; n=39; p=0.001). Patients with POTS demonstrated greater rise in norepinephrine (p=0.008) and CT-proAVP (p=0.033) on standing compared with negative HUT, and lower resting MR-proANP compared with VVS (p=0.04) and OH (p=0.03). Patients with OH had lower resting renin (p=0.03). Subjects with a resting HR <70 and MR-proANP >45 pm/L had an OR of 3.99 (95 % CI 1.68 to 9.52; p=0.002) for VVS compared with subjects without any of these criteria; if male sex was added the OR was 21.8 (95% CI 3.99 to 119; p<0.001).ConclusionsSyndromes of orthostatic intolerance and syncope share many characteristics in younger persons. However, patients with VVS are more likely to be men, have lower HR and higher MR-proANP at rest compared with POTS, which might be taken into account at an early stage of evaluation.

Background. Postural orthostatic tachycardia syndrome (POTS) is a common cardiovascular autonomic disorder characterized by excessive heart rate (HR) increase on standing and symptoms of orthostatic intolerance, posing significant limitations on functional capacity. No objective tool exists to classify symptom burden in POTS.Methods. We conducted a case-control study in 62 POTS patients and 50 healthy controls to compare symptom burden between groups using the newly developed, self-rating, 12-item, Malmö POTS Score (MAPS; 0-10 per item, total range 0-120) based on patients own perception of symptoms through visual analogue scale assessment. We have also explored correlations between symptom severity assessed by MAPS, basic clinical parameters and postural haemodynamic changes.Results. POTS patients showed significantly higher total MAPS score (78 ± 20 vs. 14 ± 12, p < 0.001), higher baseline systolic blood pressure (BP), diastolic BP and HR (p < 0.001) compared with healthy controls. The most prominent symptoms in POTS were palpitations, fatigue and concentration difficulties. Haemodynamic parameters on standing were significantly correlated with palpitations in POTS after adjustment for age and sex (lower systolic and diastolic BP, and higher HR) (p < 0.001 for all). Orthostatic HR was significantly associated with concentration difficulties and total MAPS score. The optimal cut-point value of MAPS to differentiate POTS and healthy controls was ≥42 (sensitivity, 97%; specificity, 98%).Conclusions. Symptom severity, as assessed by MAPS score, is fivefold higher in POTS compared with healthy individuals. The new MAPS score can be useful as a semiquantitative system to assess symptom burden, monitor disease progression and evaluate pre-test likelihood of disease.