Pilar Cidad

• Dr
• University of Valladolid

Introduction Coronary artery disease (CAD) is the foremost single cause of mortality and disability globally. Patients with type 2 diabetes (T2DM) have a higher incidence of CAD, and poorer prognosis. The low-grade inflammation associated to T2DM contributes to increased morbidity and worst outcomes after revascularization. Inflammatory signaling i...

Essential hypertension (HT) is a highly prevalent cardiovascular disease of unclear physiopathology. Pharmacological studies suggest that purinergic P2Y6 receptors (P2ry6) play important roles in cardiovascular function and may contribute to angiotensin II (AgtII) pathophysiological effects. Here, we tested the hypothesis that functional coupling b...

Los métodos docentes generan incertidumbre acerca de su aplicabilidad y eficacia. OBJETIVO: Mejorar el conocimiento sobre métodos docentes basado en la evidencia científica. MATERIAL Y MÉTODO: Creación de un grupo de discusión. El procedimiento de trabajo comprende la propuesta y selección de temas a estudiar, la búsqueda e identificación de estudi...

Voltage-dependent potassium channel Kv1.3 plays a key role on T-cell activation; however, lack of reliable antibodies has prevented its accurate detection under endogenous circumstances. To overcome this limitation, we created a Jurkat T-cell line with endogenous Kv1.3 channel tagged, to determine the expression, location, and changes upon activati...

Hypertension is a highly prevalent chronic disease and the major risk factor for cardiovascular diseases, the leading cause of death worldwide. Hypertension is characterized by an increased vascular tone determined by the contractile state of vascular smooth muscle cells that depends on intracellular calcium levels. The interplay of ion channels de...

Objectives Vascular occlusive disease is a leading cause of death and disability worldwide. One of the major barriers of the current surgical therapeutic approaches is restenosis of the target vessel due to dedifferentiation of the vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2DM) has a major impact on restenosis, with patients exhibitin...

Chronic kidney disease (CKD) significantly increases cardiovascular risk. In advanced CKD stages, accumulation of toxic circulating metabolites and mineral metabolism alterations triggers vascular calcification, characterized by vascular smooth muscle cell (VSMC) transdifferentiation and loss of the contractile phenotype. Phenotypic modulation of V...

The voltage‐dependent potassium channel Kv1.3 has been implicated in proliferation in many cell types, based on the observation that Kv1.3 blockers inhibited proliferation. By modulating membrane potential, cell volume, and/or Ca²⁺ influx, K⁺ channels can influence cell cycle progression. Also, noncanonical channel functions could contribute to mod...

Coronary artery disease (CAD) is the most common cardiovascular disorder. Vascular surgery strategies for coronary revascularization (either percutaneous or open) show a high rate of failure because of restenosis of the vessel, due to phenotypic switch of vascular smooth muscle cells (VSMCs) leading to proliferation and migration. We have previousl...

The modulation of voltage-gated K+ (Kv) channels, involved in cell proliferation, arises as a potential therapeutic approach for the prevention of intimal hyperplasia present in in-stent restenosis (ISR) and allograft vasculopathy (AV). We studied the effect of PAP-1, a selective blocker of Kv1.3 channels, on development of intimal hyperplasia in v...

Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human...

Objective: We have previously described that changes in the expression of Kv channels associate to phenotypic modulation (PM), so that Kv1.3/Kv1.5 ratio is a landmark of vascular smooth muscle cells phenotype. Moreover, we demonstrated that the Kv1.3 functional expression is relevant for PM in several types of vascular lesions. Here, we explore th...

Inhibition of insulin degrading enzyme has been proposed as a possible therapeutic target for type 2 diabetes treatment. However, many aspects of IDE's role in glucose homeostasis need to be clarified. In light of this, new preclinical models are required to elucidate the specific role of this protease in the main tissues related to insulin handlin...

Aims: Current risk prediction tools are not accurate enough to identify most individuals at high coronary risk. On the other hand, oxidized low-density lipoproteins (ox-LDLs) and miRNAs are actively involved in atherosclerosis. Our aim was to examine the association of ox-LDL-induced miRNAs with coronary artery disease (CAD), and to assess their pr...

The contractile state of vascular smooth muscle cells (VSMCs) in the vessel media determines vascular tone. However, these cells can undergo a phenotypic modulation (PM) towards a synthetic phenotype in response to injury. Upon PM, VSMCs lose their contractile proteins and adquire proliferative, migratory and secretory skills. PM is central to the...

In vascular smooth muscle cells (VSMCs) non‐selective cation channels such as TRPC3 and TRPC6 have been proposed as the molecular constituents of receptor‐(ROCs) and stretch‐(SOCs) operated channels linking DAG signaling cascade pathway with increased vascular tone. The membrane depolarization caused by TRPCs can increase Ca ²⁺ entry leading to aug...

Patients with chronic kidney disease (CKD) have a markedly increased incidence of cardiovascular disease (CVD). The high concentration of circulating uremic toxins and alterations in mineral metabolism and hormone levels produce vascular wall remodeling and significant vascular damage. Medial calcification is an early vascular event in CKD patients...

Kv1.3 channels are involved in the switch to proliferation of normally quiescent cells, being implicated in the control of cell cycle in many different cell types and in many different ways. They modulate membrane potential controlling K(+) fluxes, sense changes in potential and interact with many signaling molecules through their intracellular dom...

K⁺ channels encoded by the ether-a-go-go related gene (ERG1 or KCNH2) are important determinants of the cardiac action potential. Expression of both cardiac isoforms (ERG1a and ERG1b) were identified in murine portal vein and distinctive voltage-gated K⁺ currents were recorded from single myocytes. The aim of the present study was to ascertain the...

The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activa...

Key points: Canonical transient receptor potential (TRPC)3 and TRPC6 channels of vascular smooth muscle cells (VSMCs) mediate stretch- or agonist-induced cationic fluxes, contributing to membrane potential and vascular tone. Native TRPC3/C6 channels can form homo- or heterotetrameric complexes, which can hinder individual TRPC channel properties....

Changes in voltage-dependent potassium channels (Kv channels) associate to proliferation in many cell types, including transfected HEK293 cells. In this system, Kv1.5 overexpression decreases proliferation while Kv1.3 expression increases it independently of K+ fluxes. To identify Kv1.3 domains involved in proliferation-associated signaling mechani...

Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to...

Despite the substantial knowledge on the antidiabetic, antiobesity and antihypertensive actions of tungstate, information on its primary target/s is scarce. Tungstate activates both the ERK1/2 pathway and the vascular voltage- and Ca2+-dependent large-conductance BKαβ1 potassium channel, which modulates vascular smooth muscle cell (VSMC) proliferat...

Introduction: K(+) channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures. Purpose: To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of int...

Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. U...

Key points A hallmark of essential hypertension is an anomalous vascular tone due to the increase in intracellular Ca ²⁺ ([Ca ²⁺ ] i ) and/or Ca ²⁺ sensitivity in vascular smooth muscle. Down‐regulation of K ⁺ channels together with increased Ca V 1.2 channel function has been proposed as one pathogenic mechanism. Using a mouse model of essential h...

Key points Essential hypertension involves an electrical remodelling of vascular smooth muscle cells (VSMCs), particularly relevant for K ⁺ channels, as key determinants of resting membrane potential ( V M ) and excitability. We explored mRNA expression levels of inward rectifier K ⁺ channel genes in five different vascular beds from normotensive (...

Phenotypic modulation of vascular smooth muscle cells has been associated with a decreased expression of all voltage-dependent potassium channel (Kv)1 channel encoding genes but Kcna3 (which encodes Kv1.3 channels). In fact, upregulation of Kv1.3 currents seems to be important to modulate proliferation of mice femoral vascular smooth muscle cells i...

Vascular smooth muscle cell (VSMC) proliferation is involved in cardiovascular pathologies associated with unwanted arterial wall remodelling. Coordinated changes in the expression of several K+ channels have been found to be important elements in the phenotypic switch of VSMCs towards proliferation. We have previously demonstrated the association...

Vascular smooth muscle cells (VSMCs) contribute significantly to occlusive vascular diseases by virtue of their ability to switch to a noncontractile, migratory, and proliferating phenotype. Although the participation of ion channels in this phenotypic modulation (PM) has been described previously, changes in their expression are poorly defined bec...

Essential hypertension involves a gradual and sustained increase in total peripheral resistance, reflecting an increased vascular tone. This change associates with a depolarization of vascular myocytes, and relies on a change in the expression profile of voltage-dependent ion channels (mainly Ca(2+) and K(+) channels) that promotes arterial contrac...

Vascular smooth muscle cells (VSMCs) perform diverse functions that can be classified into contractile and synthetic (or proliferating). All of these functions can be fulfilled by the same cell because of its capacity of phenotypic modulation in response to environmental changes. The resting membrane potential is a key determinant for both contract...

There is an increasing body of evidence demonstrating that inhibition of cytochrome c oxidase by nitric oxide (NO) may be one more step in a signaling cascade involved in the physiologic regulation of cell functions. For example, in both astrocytes and neurons the inhibition of mitochondrial respiration by endogenously produced NO induces transient...

It is well known that the brain is a vulnerable organ that depends on an efficient supply of oxygen and energetic substrates from the blood. Thus, a transient lapse in such supply may lead to unconsciousness and, after only a few minutes, to irreversible alterations possibly causing neuronal death [1]. In fact, neurotransmission is one of highest e...

Recently, we have reported that the inhibition of mitochondrial respiration by nitric oxide (NO) leads to an up-regulation of glycolysis and affords cytoprotection against energy failure through the stimulation of AMPK (5'-AMP-activated protein kinase) [Almeida, Moncada and Bolanos (2004) Nat. Cell Biol. 6, 45-51]. To determine whether glucose tran...

Following brain inflammatory stimuli, astrocytes actively synthesize nitric oxide and peroxynitrite. These nitrogen-derived species trigger a repertoire of biochemical effects, including alteration of mitochondrial function and redox status both in astrocytes and neighboring neurons. Furthermore, under such nitrosative stress astrocytes show remark...

The possible interference of nitric oxide (NO) in glucose metabolism was studied in activated astrocytes. Lipopolysaccharide (LPS) treatment triggered a NO-mediated increase in glucose consumption and lactate production, suggesting an enhanced rate of glycolysis. Active glycogen synthesis was also observed after LPS treatment, but NO synthase inhib...

It has been shown that actin genes exhibit distinct tissue and stage-specific patterns of expression. We have cloned a new β-actin gene from the teleost zebrafish (Danio rerio), a well-established model for developmental studies, and analysed its expression by Northern blot and in situ hybridization studies. Our results suggest that in adult brain...