The impairment of endocardial radial strain is related to aortic stenosis severity in patients with aortic stenosis and preserved LV ejection fraction using two-dimensional speckle tracking echocardiography.

BACKGROUND: Myocardial function is heterogeneous in different myocardial layers. Recently, two-dimensional speckle tracking echocardiography has been used to define myocardial deformation parameters of the left ventricular (LV) segment. This study aimed to investigate strain in subendocardial and subepicardial layers in patients with aortic stenosis (AS) and preserved LV ejection fraction (LVEF) using speckle tracking echocardiography. METHODS: Parasternal short-axis and apical long-axis views of the left ventricle were acquired at the mid-papillary level in 35 control subjects and 32 patients with AS and preserved LVEF. Radial, circumferential, and longitudinal strain in subendocardial and subepicardial layers at the posterior and anteroseptal segments were calculated. RESULTS: There was no significant difference in circumferential strain in subendocardial and subepicardial layers between the control subjects and the patients with AS. Similarly, there was no significant difference in epicardial radial strain at the posterior and anteroseptal segments between the control subjects and the patients with AS. Longitudinal strain at both the posterior and anteroseptal segments was significantly decreased in the AS group compared with that in the control group. AS patients had significantly decreased values of endocardial radial strain compared with those in controls (anteroseptal: 18.2 ± 11.2 vs. 34.5 ± 14.8, P < 0.005; posterior: 25.2 ± 14.8 vs. 32.6 ± 12.6, P < 0.05). In the AS group, endocardial radial strain in the posterior and anteroseptal segments was significantly correlated with the aortic valve area (posterior: r = 0.41, P < 0.05; anteroseptal: r = 0.33, P < 0.05). CONCLUSION: Patients with AS and preserved LVEF have impaired longitudinal strain and endocardial radial strain, although circumferential strain and epicardial radial strain are preserved. Despite preserved LVEF, endocardial radial strain was associated with AS severity.

Activation of the VIP/VPAC2 system induces reactive astrocytosis associated with increased expression of glutamate transporters.

Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide that acts as a neuromodulator in the CNS. Recently, secretion of several functional molecules has been identified in VIP-stimulated astrocytes in vitro. However, the relationship between VIP and its specific receptors in neurological disorders remains unknown. To investigate the role of the VIP system under pathological conditions, we performed a cold injury on the right cerebrum of adult C57BL/6 mice and observed expression patterns for VIP and its receptor, VPAC2. Immunohistochemical studies revealed VPAC2 expression in reactive astrocytes around the core lesion by post-injury day 7, which then returned to contralateral levels at post-injury day 14. By contrast, VIP immunoreactivity was detected in activated microglial cells, suggesting that microglia-astrocyte interactions in the VIP/VPAC2 system are important for the tissue repair process. In primary cultured astrocytes stimulated with N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate sodium salt (dbcAMP) to mimic reactive astrocytosis, VPAC2 mRNA expression was highly up-regulated compared to that of the other VIP receptors, PAC1 and VPAC1. VPAC2 activation by the selective VPAC2 agonist, Ro25-1553, induced reactive morphological and biochemical changes from a polygonal shape to a stellate shape in cultured astrocytes. Further, Ro25-1553 increased cell surface expression of the glutamate transporters GLAST and GLT-1, which can limit excitotoxic neuronal cell death. In summary, the transient expression of VPAC2 in reactive astrocytes and the up-regulation of functional glutamate transporters suggest that the VIP/VPAC2 system induces reactive astrocytosis and plays a key role in neuroprotection against excitotoxicity in neurological disorders.

Successful treatment in a case of acute myocardial infarction due to spontaneous coronary artery dissection.

Spontaneous coronary dissection is a rare cause of myocardial ischemia, myocardial infarction, and sudden death. In the present case, we performed stenting only of the severe stenotic lesion of the dissection with a short bare metal stent, and left the remaining long length of dissection vessel untreated. Six months after coronary stenting, follow-up angiography revealed complete healing of the coronary dissection and no significant in-stent restenosis. This case clearly demonstrates the usefulness of intravascular ultrasound (IVUS) imaging in the diagnosis of coronary dissection and IVUS imaging guides to the choice of the best stenting.

Cor triatriatum sinister disclosed after diagnosis of acute myocardial infarction.

We present a case of cor triatriatum sinister diagnosed occasionally after acute anterior myocardial infarction. For management of the acute myocardial infarction (AMI), urgent reperfusion therapy was successfully performed through the left anterior descending coronary artery. Thereafter, no complication associated with AMI occurred. Cor triatriatum sinister was diagnosed and assessed later by means of several modalities. Finally, medical observation was indicated for this patient. This case illustrates the importance of awareness of this congenital disease in an adult when echocardiography shows an abnormal linear echo in the mid portion of the left atrium.

Alpha 1-adrenoceptor agonists protect against stress-induced death of neural progenitor cells.

Here, we show that alpha(1)-adrenoceptor agonists suppress stress-induced death of mouse embryonic brain-derived neural progenitor cells (NPCs). NPCs highly expressed both alpha(1A)- and alpha(1B)-adrenoceptor genes, whereas the gene encoding alpha(1D)-adrenoceptor was expressed at low levels. Application of the alpha(1)-adrenoceptor agonists phenylephrine and cirazoline significantly promoted cell survival of embryonic NPCs that had been exposed to stress, as measured by a lactate dehydrogenase release assay, but had no remarkable effect on differentiation of the NPCs. Both phenylephrine and cirazoline protected NPCs from death induced by growth factor deprivation, N2 nutrient deprivation, tunicamycin treatment or staurosporine treatment. Phenylephrine and cirazoline treatments both maximally reduced stress-induced cell death by approximately 60% but did not change the percentage of undifferentiated cells as measured by nestin staining. Moreover, phenylephrine and cirazoline treatments did not affect the cellular activities of caspase-3 and caspase-7 but markedly reduced propidium iodide penetration into the cytoplasm, suggesting that alpha(1)-adrenoceptor agonists inhibit caspase-3/7-independent death of the embryonic NPCs.

PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells.

The Pituitary adenylate cyclase-activating peptide (PACAP) ligand/type 1 receptor (PAC1) system regulates neurogenesis and gliogenesis. It has been well established that the PACAP/PAC1 system induces differentiation of neural progenitor cells (NPCs) through the Gs-mediated cAMP-dependent signaling pathway. However, it is unknown whether this ligand/receptor system has a function in proliferation of NPCs. In this study, we identified that PACAP and PAC1 were highly expressed and co-localized in NPCs of mouse cortex at embryonic day 14.5 (E14.5) and found that the PACAP/PAC1 system potentiated growth factor-induced proliferation of mouse cortical NPCs at E14.5 via Gq-, but not Gs-, mediated PLC/IP3-dependent signaling pathway in an autocrine manner. Moreover, PAC1 activation induced elongation of cellular processes and a stellate morphology in astrocytes that had the bromodeoxyuridine (BrdU)-incorporating ability of NPCs. Consistent with this notion, we determined that the most BrdU positive NPCs differentiated to astrocytes through PAC1 signaling. These results suggest that the PACAP/PAC1 system may play a dual role in neural/glial progenitor cells not only differentiation but also proliferation in the cortical astrocyte lineage via Ca2+-dependent signaling pathways through PAC1.

Ubiquitin C-terminal hydrolase L1 regulates the morphology of neural progenitor cells and modulates their differentiation.

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a component of the ubiquitin system, which has a fundamental role in regulating various biological activities. However, the functional role of the ubiquitin system in neurogenesis is not known. Here we show that UCH-L1 regulates the morphology of neural progenitor cells (NPCs) and mediates neurogenesis. UCH-L1 was expressed in cultured NPCs as well as in embryonic brain. Its expression pattern in the ventricular zone (VZ) changed between embryonic day (E) 14 and E16, which corresponds to the transition from neurogenesis to gliogenesis. At E14, UCH-L1 was highly expressed in the ventricular zone, where neurogenesis actively occurs; whereas its expression was prominent in the cortical plate at E16. UCH-L1 was very weakly detected in the VZ at E16, which corresponds to the start of gliogenesis. In cultured proliferating NPCs, UCH-L1 was co-expressed with nestin, a marker of undifferentiated cells. In differentiating cells, UCH-L1 was highly co-expressed with the early neuronal marker TuJ1. Furthermore, when UCH-L1 was induced in nestin-positive progenitor cells, the number and length of cellular processes of the progenitors decreased, suggesting that the progenitor cells were differentiating. In addition, NPCs derived from gad (UCH-L1-deficient) mice had longer processes compared with controls. The ability of UCH-L1 to regulate the morphology of nestin-positive progenitors was dependent on its binding affinity for ubiquitin but not on hydrolase activity; this result was also confirmed using gad-mouse-derived NPCs. These results suggest that UCH-L1 spatially mediates and enhances neurogenesis in the embryonic brain by regulating progenitor cell morphology.