Proteome landscape and interactome of voltage-gated potassium channel 1.6 (Kv1.6) of the murine ophthalmic artery and neuroretina.

The voltage-gated potassium channel 1.6 (Kv1.6) plays a vital role in ocular neurovascular beds and exerts its modulatory functions via interaction with other proteins. However, the interactome and their potential roles remain unknown. Here, the global proteome landscape of the ophthalmic artery (OA) and neuroretina was mapped, followed by the determination of Kv1.6 interactome and validation of its functionality and cellular localization. Microfluorimetric analysis of intracellular [K+] and Western blot validated the native functionality and cellular expression of the recombinant Kv1.6 channel protein. A total of 54, 9 and 28 Kv1.6-interacting proteins were identified in the mouse OA and, retina of mouse and rat, respectively. The Kv1.6-protein partners in the OA, namely actin cytoplasmic 2, alpha-2-macroglobulin and apolipoprotein A-I, were implicated in the maintenance of blood vessel integrity by regulating integrin-mediated adhesion to extracellular matrix and Ca2+ flux. Many retinal protein interactors, particularly the ADP/ATP translocase 2 and cytoskeleton protein tubulin, were involved in endoplasmic reticulum stress response and cell viability. Three common interactors were found in all samples comprising heat shock cognate 71 kDa protein, Ig heavy constant gamma 1 and Kv1.6 channel. This foremost in-depth investigation enriched and identified the elusive Kv1.6 channel and, elucidated its complex interactome.

Ophthalmic artery Doppler for pre-eclampsia prediction at the first trimester: a Bayesian survival-time model.

OBJECTIVE: To develop a Bayesian survival-time model for the prediction of pre-eclampsia (PE) at the first trimester using a combination of established biomarkers including maternal characteristics and history, mean arterial pressure (MAP), uterine artery Doppler pulsatility index (UtA-PI), and Placental Growth Factor (PlGF)) with an ophthalmic artery Doppler peak ratio (PR) analysis. METHODS: The receiving operator curve (ROC) analysis was used to determine the area under the curve (AUC), detection rate (DR), and positive screening cut-off value of the model in predicting the occurrence of early-onset PE (< 34 weeks' gestation) and preterm PE (< 37 weeks' gestation). RESULTS: Of the 946 eligible participants, 71 (7.49%) subjects were affected by PE. The incidences of early-onset and preterm PE were 1% and 2.2%, respectively. At a 10% false-positive rate, using the high-risk cut-off 1:49, with AUC 0.981 and 95%CI 0.965-0.998, this model had an 100% of DR in predicting early-onset PE. The DR of this model in predicting preterm PE is 71% when using 1:13 as the cut-off, with AUC 0.919 and 95%CI 0.875-0.963. CONCLUSION: Combination ophthalmic artery Doppler PR with the previously established biomarkers could improve the accuracy of early and preterm PE prediction at the first trimester screening.

Spironolactone reduces cerebral infarct size and EGF-receptor mRNA in stroke-prone rats.

Remodeling of the cerebral vasculature contributes to the pathogenesis of cerebral ischemia. Remodeling is caused by increased smooth muscle proliferation and may be due to an increase in the responsiveness of vascular cells to epidermal growth factor (EGF). Aldosterone is a risk factor for stroke, and the literature suggests it may play a role in increasing the expression of the receptor for EGF (EGFR). We hypothesized that mRNA for the EGF-stimulated pathway would be elevated in the vasculature of stroke-prone spontaneously hypertensive rats (SHRSP) and that this and experimental ischemic cerebral infract size would be reduced by aldosterone inhibition with spironolactone. We found that spironolactone treatment reduced the size of cerebral infarcts after middle cerebral artery occlusion in SHRSP (51.69 +/- 3.60 vs. 22.00 +/- 6.69% of hemisphere-infarcted SHRSP vs. SHRSP + spironolactone P < 0.05). Expression of EGF and EGFR mRNA was higher in cerebral vessels and aorta from adult SHRSP compared with Wistar-Kyoto rats. Only the expression of EGFR mRNA was elevated in the young SHRSP. Spironolactone reduced the EGFR mRNA expression in the aorta (1.09 +/- 0.25 vs. 0.56 +/- 0.11 phosphorimage units SHRSP vs. SHRSP + spironolactone P < 0.05) but had no effect on EGF mRNA. In vitro incubation of aorta with aldosterone +/- spironolactone produced similar results, suggesting a direct effect of aldosterone. Thus spironolactone may reduce the size of cerebral infarcts via a reduction in the expression of the EGFR mRNA, leading to reduced remodeling.