Objective-All 3 isoforms of the nitric oxide synthase (NOS) are expressed in atherosclerotic lesions. To test whether neuronal NOS (nNOS) deficiency affects atherosclerosis, we studied apoE/nNOS␣ double knockout (DKO) and apolipoprotein E (apoE) knockout (KO) control mice. Methods and Results-Lesion area was significantly increased in male DKO (66%) mice after 14 weeks and in female DKO animals (31%) after 24 weeks of "western" diet. Moreover, mean arterial blood pressure was significantly reduced in female DKO animals. Immunohistochemistry revealed nNOS expression in the neointima of KO mice. In DKO animals, residual nNOS staining was caused by the presence of nNOS splice variants. Whereas nNOS␣ was present in vessels of KO and absent in DKO animals, nNOS␥ was expressed in KO and DKO mice. Conclusion-nNOS␣ protects against atherosclerosis as nNOS␣ deletion leads to an increase in plaque formation in apoE/nNOS␣ DKO mice. Female DKO mice showed a significant reduction in mean arterial blood pressure. Additionally, we found expression of nNOS splice variants in vessels of apoE KO mice. Our data highlights nNOS␣ overexpression as a potential therapeutic strategy and naturally occurring splice variants that lack exon 2 of the nNOS gene as a potential risk factor for vascular disease. Key Words: nitric oxide Ⅲ nitric oxide synthase Ⅲ arteriosclerosis Ⅲ blood pressure Ⅲ gene expression N euronal nitric oxide synthase (nNOS) is expressed in early and advanced human atherosclerotic lesions. 1 Immunolocalization and in situ hybridization revealed nNOS expression in endothelial cells, macrophages, and smooth muscle cells. In addition, nNOS expression is found in perivascular nitrinergic neurons. [2][3][4] Although nNOS and endothelial nitric oxide synthase (eNOS) are termed constitutive NOS isoforms, nNOS is only detectable in intact human vessels using supersensitive methods, suggesting that expression may be induced in atherosclerosis. 1,5 The nNOS gene produces multiple mRNA splice variants through various mechanisms, namely alternate promotor usage, alternative See page 1417splicing, cassette insertion and deletions, and varied sites of 3Ј-UTR cleavage and polyadenylation. 6 These mechanisms lead to 4 different peptides, of which 2 have a PDZ domain that anchors them to the sarcoplasmic reticulum, whereas 2 lack the PDZ-domain, localizing them to the cytosol. 6 Schwarz et al reported the presence of small amounts of brain-type nNOS␣ and muscle-type nNOS in the media and adventitia of rat aorta and showed that nNOS may exert an inhibitory effect against a vasoconstrictive response. 7 Recent studies in a mouse carotid artery ligation model, as well as a rat model of balloon induced vascular injury, demonstrated that nNOS is expressed after vascular injury and inhibits intima proliferation, pointing toward a vasculoprotective role of nNOS. 8 So far, the relevance of nNOS expression in spontaneous plaque formation has not been addressed. To study the relative contribution of nNOS to lesion formation, we combined a genetic...

Objective-Hypercholesterolemia is associated with decreased vascular nitric oxide bioavailability and deletion of endothelial nitric oxide synthase (eNOS) markedly accelerates atherosclerosis development in apolipoprotein E knockout (apoE ko) mice. The current study tests whether atheroprotection provided by a lipid lowering therapy with Ezetimibe depends on eNOS.Methods/Results-ApoE ko and apoE/eNOS double ko (dko) mice received a high fat diet with or without 0.05% Ezetimibe. Ezetimibe significantly reduced plasma cholesterol concentrations and atherogenic lipoproteins in both genotypes to a similar extent. Moreover, the drug reduced vascular inflammation, as it significantly reduced Vascular Cell Adhesion Molecule-1 (VCAM-1) expression and vascular CD14 expression, a marker for mononuclear cell infiltration, in both genotypes. Neither NOS protein expression nor vascular reactivity of aortic rings were changed in apoE ko mice following Ezetimibe treatment. Significant lesion reduction was seen in Ezetimibe treated male and female apoE ko and apoE/eNOS dko animals (p≤0.05). Interestingly, the drug mediated additional atheroprotection in male apoE ko, compared to male eNOS dko mice, suggesting that lipid lowering does provide additional eNOS dependent atheroprotection in this experimental group.Conclusion-Lipid lowering with Ezetimibe potently reduces atherosclerosis and vascular inflammation independent of eNOS. Moreover, Ezetimibe did not exert any effects on eNOS protein expression or enzyme activity. However, additional atheroprotection by Ezetimibe was observed in eNOS competent apoE ko mice, suggesting that some of the drug's antiatherosclerotic effects are mediated by the eNOS pathway.

Introduction: Telemedicine gained an increasing use throughout the last years. Lifestyle tools like the Apple watch seem to have an increasing spread even in remote areas and underdeveloped regions. The increasing availability of these tools offers the chance to use the health care functions of these devices to improve provision of professional medical care. First data on the use of the Apple Watch as a remote monitoring device in children have been reported, showing good acceptability and usability of the Apple Watch for symptom monitoring in children. This study aimed to evaluate the accuracy of the Apple Watch iECG in comparison to a standard 12-lead ECG in pre-term babies. Methods: In this prospective, single-arm study, consecutive preterm neonates hospitalised in Leipzig University Hospital neonatal ICU were eligible. A 12-lead ECG and an iECG using Apple Watch 4 were performed. iECG and 12-lead ECG measurements were performed by a paediatric cardiologist. Cardiac rhythm was classified and amplitudes and timing intervals were analysed for comparability. Results: Fifty preterm neonates, gestational week (23–36 weeks), and body weight (0.65–3.09 kg) were enrolled. Overall good quality and excellent correlation of the Apple Watch generated iECG in comparison to the standard 12-lead ECG could be demonstrated (p < 0.001). When interpreted by a paediatric cardiologist, a correct rhythm classification could be done in 100% of cases. Conclusion: The Apple Watch iECG seems to be a valuable tool to record an ECG comparable to lead I of the standard 12-lead ECG even in pre-term neonates. With a widespread availability and excellent connectivity, the Apple Watch iECG function may provide practitioners with a tool to send an iECG for interpretation to a paediatric cardiac specialist.

We generalize the joint time-frequency von Neumann representation of femtosecond laser pulses for usage with time-dependent polarization states. The electric field is expanded in terms of Gaussian-shaped transform-limited subpulses located on a discrete time-frequency lattice, each with a specific polarization state. This formalism provides an intuitive picture for the time-and frequency-dependent polarization state. It can also serve as a basis for polarization pulse shaping. As an illustration, we define pulses for which polarization parameters (ellipticity and orientation) are given directly in time-frequency phase space. This approach has applications in quantum control and other areas for which time-and frequency-dependent light polarization is relevant.