Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps.

T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.

Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps-A Systematic Review.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nose and paranasal sinuses characterized by the presence of nasal polyps. The symptoms produced by the presence of nasal polyps such as nasal obstruction, nasal discharge, facial pain, headache, and loss of smell cause a worsening in the quality of life of patients. The source of the nasal polyps remains unclear, although it seems to be due to a chronic inflammation process in the sinonasal mucosa.

Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

Background: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed.

Usefulness of bilateral mucoplasty plus reboot surgery in severe type-2 chronic rhinosinusitis with nasal polyps.

Background: Although extended endoscopic sinus surgery (ESS) constitutes an alternative approach in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), the surgical techniques proposed so far do not allow for an optimal control of the disease. This study introduces bilateral mucoplasty as a complementary technique to extended ESS such as reboot surgery, analyzing its benefits in healing and quality of life (QoL).

Methods: Patients diagnosed with severe Type-2 CRSwNP were selected for a prospective cohort study in two surgery groups: reboot surgery plus bilateral mucoplasty versus reboot surgery only.

PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition.

Background/aims: Protein kinase C (PKC)- and RhoA/Rho-associated kinase (ROCK) play important roles in arterial sustained contraction. Although depolarization-elicited RhoA/ROCK activation is accepted, the role of PKC in depolarized vascular smooth muscle cells (VSMCs) is a subject of controversy. Our aim was to study the role of PKC in arterial contraction and its interaction with RhoA/ROCK.

Contribution of L-type Ca channel-sarcoplasmic reticulum coupling to depolarization-induced arterial contraction in spontaneously hypertensive rats.

Evidence has shown that vascular smooth muscle cells (VSMCs) of spontaneously hypertensive rats (SHRs) are depolarized and that the expression of L-type Ca channels (LTCCs) and the sarcoplasmic reticulum (SR) Ca buffering system are upregulated. Arterial rings exposed to high K solutions develop a contraction with two components, namely, an initial or phasic component and a sustained or tonic component. Because LTCCs and SR have different functions in the phasic and tonic components of depolarization-induced contraction, this study investigated the role of LTCC-SR coupling in depolarized arterial rings of SHRs.

Regulation of RhoA/ROCK and sustained arterial contraction by low cytosolic Ca levels during prolonged depolarization of arterial smooth muscle.

The role of L-type Ca channels (LTCCs) and RhoA/Rho kinase (ROCK) on depolarization-induced sustained arterial contraction lasting several minutes is already known. However, in vivo, vascular smooth muscle cells can be depolarized for longer periods, inducing substantial inactivation of LTCCs and markedly reducing Ca influx into the myocytes. We have examined, in femoral arterial rings, the role of LTCCs and RhoA/ROCK during long-lasting depolarization.

Role of L-type Ca(2+) channels, sarcoplasmic reticulum and Rho kinase in rat basilar artery contractile properties in a new model of subarachnoid hemorrhage.

We have previously described that L-type Ca(2+) channels' (LTCCs) activation and metabotropic Ca(2+) release from the sarcoplasmic reticulum (SR) regulate RhoA/Rho kinase (ROCK) activity and sustained arterial contraction. We have investigated whether this signaling pathway can be altered in a new experimental model of subarachnoid hemorrhage (SAH). For this purpose, arterial reactivity was evaluated on days 1 to 5 after surgery.

Low-dose combination of Rho kinase and L-type Ca(2+) channel antagonists for selective inhibition of depolarization-induced sustained arterial contraction.

L-type Ca(2+) channels (LTCCs) are involved in the maintenance of tonic arterial contractions and regulate the RhoA/Rho-associated kinase (ROCK) sensitization cascade. We have tested effects of individual and combined low concentrations of LTCCs and ROCK inhibitors to produce arterial relaxation without the adverse side effects of LTCCs antagonists. We have also studied whether this pharmacological strategy alters Ca(2+)-dependent electrical properties of isolated arterial and cardiac myocytes as well as cardiac contractility.

Contractile responses to rat urotensin II in resting and depolarized basilar arteries.

The effects of human urotensin II (hUII) on the vascular tone of different animal species has been studied extensively. However, little has been reported on the vasoactive effects of rat urotensin (rUII) in murine models. The aim of the present study was to investigate the effects of rUII on vasoreactivity in rat basilar arteries.

A new metabotropic role for L-type Ca(2+) channels in vascular smooth muscle contraction.

Vascular smooth muscle cells (VSMCs) contraction can be evoked by the rise of cytosolic [Ca(2+)] owing to transmembrane Ca(2+) influx or sarcoplasmic reticulum (SR) Ca(2+) release. Although the classical ionotropic role of voltagedependent (L-type) Ca(2+) channels (VGCCs) is known, we review here data suggesting a new metabotropic function of VGCCs in vascular smooth muscle cells. VGCCs can trigger Ca(2+) release from the SR in the absence of extracellular Ca2+.

Tonic arterial contraction mediated by L-type Ca2+ channels requires sustained Ca2+ influx, G protein-associated Ca2+ release, and RhoA/ROCK activation.

KCl-evoked sustained contraction requires L-type Ca(2+) channel activation, metabotropic Ca(2+) release from the sarcoplasmic reticulum (mechanism denoted calcium channel-induced Ca(2+) release) and RhoA/Rho associated kinase activation. Although high K(+) solutions are used to depolarize myocytes, these solutions can stimulate other signaling pathways such as those triggered by the activation of muscarinic and purinergic receptors. The present study examines the functional role of calcium channel-induced Ca(2+) release under pharmacological activation of L-type Ca(2+) channel without significant membrane depolarization.

Tungstate activates BK channels in a β subunit- and Mg2+-dependent manner: relevance for arterial vasodilatation.

Aims: Tungstate reduces blood pressure in experimental animal models of both hypertension and metabolic syndrome, although the underlying mechanisms are not fully understood. Given that the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel is a key element in the control of arterial tone, our aim was to evaluate whether BK channel modulation by tungstate can contribute to its antihypertensive effect.

Methods And Results: Patch-clamp studies of heterologously expressed human BK channels (α + β(1-4) subunits) revealed that cytosolic tungstate (1 mM) induced a significant left shift (∼20 mV) in the voltage-dependent activation curve only in BK channels containing αβ(1) or αβ(4) subunits, but reduced the amplitude of K(+) currents through all BK channels tested.

Metabotropic regulation of RhoA/Rho-associated kinase by L-type Ca2+ channels: new mechanism for depolarization-evoked mammalian arterial contraction.

Background: Sustained vascular smooth muscle contraction is mediated by extracellular Ca(2+) influx through L-type voltage-gated Ca(2+) channels (VGCC) and RhoA/Rho-associated kinase (ROCK)-dependent Ca(2+) sensitization of the contractile machinery. VGCC activation can also trigger an ion-independent metabotropic pathway that involves G-protein/phospholipase C activation, inositol 1,4,5-trisphosphate synthesis, and Ca(2+) release from the sarcoplasmic reticulum (calcium channel-induced Ca(2+) release). We have studied the functional role of calcium channel-induced Ca(2+) release and the inter-relations between Ca(2+) channel and RhoA/ROCK activation.