Luis Michea

University of Chile · Facultad de Medicina

End-stage renal disease (ESRD) patients are a population with high rates of COVID-19 and mortality. These patients present a low response to anti-SARS-CoV-2 immunization, which is associated with immune dysfunction. ESRD patients also present high plasma titers of Fibroblast Growth Factor 23 (FGF23), a protein hormone that reduces immune response i...

RESUMEN Objetivo Evaluar la eficacia de un protocolo estandarizado y simplificado basado en los pilares técnicos de la Iniciativa HEARTS para el control de pacientes hipertensos del Programa de Salud Cardiovascular en el primer nivel de atención de salud en Chile. Métodos Estudio observacional longitudinal (cohorte histórica), en 2 centros de sal...

Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antio...

Background/aims: Renal ischemia and reperfusion injury (IRI) involves oxidative stress, disruption of microvasculature due to endothelial cell damage, loss of epithelial cell polarity secondary to cytoskeletal alterations, inflammation, and the subsequent transition into a mesenchymal phenotype. Ischemic preconditioning (IPC) has been proposed as...

Objectives: As part of the HEARTS in the Americas initiative, Chilean primary healthcare centers have implemented novel hypertension management strategies, including new diagnostic approaches. This study evaluated the concordance between attended automated office blood pressure (AOBP) measurements with an oscillometric device and ambulatory blood...

Even though the mechanisms that mediate essential hypertension (HT) are not fully understood, an immunological-inflammatory mechanism could be the common pathway for diverse pathophysiological mechanisms. We analyze in a simplified way the participation of the immune system in HT. T lymphocytes (TL) and antigen presenting cells (APCs) are component...

Colony formation assay in cells transduced with Ski mutants. And model for centrosome amplification following tetraploidy

Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in paediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GC) reduces bone growth and mineral density. The mechanisms causing GC‐induced growth impairment have not been fully clarified. Fibroblast growth facto...

Background: Adaptive immunity is crucial in cardiovascular and renal inflammation/fibrosis upon hyperactivation of mineralocorticoid receptor. We have previously demonstrated that dendritic cells can respond to mineralocorticoid receptor activation, and the neutrophil gelatinase-associated lipocalin (NGAL) in dendritic cells is highly increased dur...

On renal ischemia-reperfusion (I/R) injury, recruitment of neutrophils during the inflammatory process promotes local generation of oxygen and nitrogen reactive species, which, in turn, are likely to exacerbate tissue damage. The mechanism by which inducible nitric oxide synthase (iNOS) is involved in I/R has not been elucidated. In this work, the...

Transient Receptor Potential Melastatin 4 (TRPM4) is a Ca²⁺‐activated and voltage‐dependent monovalent cation channel, which depolarizes the plasma cell membrane, thereby modulating Ca²⁺ influx across Ca²⁺‐permeable pathways. TRPM4 is involved in different physiological processes such as T cell activation and the migration of endothelial and certai...

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma F...

Increasing evidence shows that antigen-presenting cells (APCs) are involved in the development of inflammation associated to hypertension. However, the potential role of APCs in the modulation of renal sodium transport has not been addressed. We hypothesized that APCs participate in renal sodium transport and, thus, development of high blood pressu...

Renal sodium reabsorption depends on the activity of the Na⁺,K⁺-ATPase α/β heterodimer. Four α (α1-4) and three β (β1-3) subunit isoforms have been described. It is accepted that renal tubule cells express α1/β1 dimers. Aldosterone stimulates Na⁺,K⁺-ATPase activity and may modulate α1/β1 expression. However, some studies suggest the presence of β3...

Introduction: Describe the experience of clinical presentation, diagnostic study, and treatment of patients with tumor-induced osteomalacia (TIO) in a South American academic center in comparison to literature. Methods: Analysis of the records of patients diagnosed with TIO. The clinical presentation, diagnostic studies, and treatment were analy...

Oncogenic kinase Aurora A (AURKA) has been found to be overexpresed in several tumors including colorectal, breast and hematological cancers. Overexpression of AURKA induces centrosome amplification and aneuploidy and it is related with cancer progression and poor prognosis. Here we show that AURKA phosphorylates in vitro the transcripcional co-rep...

Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ)-mediated intercellular communication are implicated in cancer pathogenesis. Herein, we have investigated the role of Cx43 in melanoma cell proliferation and apoptosis sensitivity in vitro, as well as metastatic capability and tumour growth in vivo. Connexin 43 expression levels,...

Na(+)/I(-) symporter (NIS) mediates iodide (I(-)) uptake in the thyroid gland, the first and rate limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyroid cells is mainly regulated by the thyroid stimulating hormone (TSH) and by the intracellular concentration of I(-). High doses of I(-) for 1 or 2 da...

Background: Angiotensin-(1-9) has anti-hypertensive properties and protective cardiovascular effect in hypertensive rats. However, it is unknown whether its effects are related to a kidney mechanism to balance sodium. Aim: To determine if the anti-hypertensive effect of Ang-(1-9) is associated to a diuretic-natriuretic mechanism. Method: Sprague Da...

Rac1 upregulation has been implicated in salt-sensitive hypertension as a modulator of mineralocorticoid receptor (MR) activity. Rac1 could affect the expression of oxidative stress markers, such as hemoxigenase-1 (HO-1) or nuclear factor-B (NF-κB), and the expression of neutrophil gelatinase-associated lipocalin (NGAL), a cytokine upregulated upon...

Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [a...

Little is known about the biological effects of angiotensin-(1-9), but available evidence shows that angiotensin-(1-9) has beneficial effects in preventing/ameliorating cardiovascular remodeling. In this study, we evaluated whether angiotensin-(1-9) decreases hypertension and reverses experimental cardiovascular damage in the rat. Angiotensin-(1-9)...

Adaptive immune response has been implicated in inflammation and fibrosis as a result of exposure to mineralocorticoids and a high-salt diet. We hypothesized that in mineralocorticoid-salt-induced hypertension, activation of the mineralocorticoid receptor alters the T-helper 17 lymphocyte (Th17)/regulatory T-lymphocyte/interleukin-17 (IL-17) pathwa...

Previously, we found in experimental hypertension (DOCA salt model), that the RhoA/Rho-kinase pathway inhibition by fasudil decreases hypertension (HT), angiotensin (Ang) II levels and vascular remodeling. Besides, in this model fasudil increased ACE2 activity and Ang1-9 plasma levels. These results strongly suggest that in this experimental model,...

Background: Glucocorticoid immunosuppressant therapy in pediatric kidney transplant (Tx) recipients does not allow the improvement of growth after Tx. Objective: To determine the effect of early steroid withdrawal (SW) on longitudinal growth, insulin sensitivity (IS), and body composition (BC). Methods: This was a prospective, randomized, mult...

Differentiation of vascular smooth muscle cells (VSMC) is an essential process of vascular development. VSMC have biosynthetic, proliferative, and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMC play a critical role in the pathogenesis of atherosclerosis and intimal hyperplasia, as well as in a variety of o...

To determine whether maternal plasma levels of 2-methoxyestradiol (2-ME) are decreased early in pregnancies that subsequently develop pre-eclampsia (PE) and whether this difference could be attributed to the presence of Val158Met catechol-O-methyltransferase (COMT) polymorphism in the placenta. Clinical characteristics and plasma samples were colle...

Th17 cells, a recently described subtype of CD4+ effector lymphocytes, have been linked to cell-mediated autoimmune and inflammatory diseases as well as to cardiovascular diseases. However, the participation of IL-17A in myocardial ischemic injury has not been clearly defined. We therefore conducted the present study to evaluate IL-17A and Th17-rel...

Background: Recently, we proposed that Angiotensin (Ang)-[1-9] prevents the hypertension (HT) and exerts cardioprotective effect in the heart probably by antagonizing AngII actions. We hypothesized here that Ang-(1-9) rather than Ang-(1-7), reduces HT and vascular remodeling through AT2 receptor blocker (AT2R) and eNOS. Objective: To determine the...

The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10-18 mmHg); however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial...

Hemodialysis patients (HD) display high rates of cardiac disease and mortality. The cardiovascular morbidity and mortality of HD patients is attributable in a significant proportion to endothelial dysfunction, arterial stiffness, and vascular calcifications. To measure vascular reactivity in HD subjects and compare them with healthy volunteers. For...

Background: Hemodialysis patients (HD) display high rates of cardiac disease and mortality. The cardiovascular morbidity and mortality of HD patients is attributable in a significant proportion to endothelial dysfunction, arterial stiffness, and vascular calcifications. Aim: To measure vascular reactivity in HD subjects and compare them with health...

The study by Taylor et al published in June 2010 in the American Journal of Hypertension questions the effectiveness of reducing salt intake in the diet in the prevention and treatment of high blood pressure and other cardiovascular conditions. The publication of this article has lead to great controversy and medical associations and learned societ...

La población envejece en forma acelerada, y la comprensión de los cambios fisiológicos asociados al envejecimiento es una herramienta importante para enfrentar las demandas biomédicas y sociales de ese grupo etario. El objetivo de la presente revisión es definir los principales cambios morfológicos y funcionales en los sistemas cardiovascular, rena...

The study by Taylor et al published in June 2010 in the American Journal of Hypertension questions the effectiveness of reducing salt intake in the diet in the prevention and treatment of high blood pressure and other cardiovascular conditions. The publication of this article has lead to great controversy and medical associations and learned societ...

Th17 cells, a recently described subtype of CD4+ effector lymphocytes, have been linked to cell-mediated autoimmune and inflammatory diseases as well as to cardiovascular diseases. However, the participation of IL-17A in myocardial ischemic injury has not been clearly defined. We therefore conducted the present study to evaluate IL-17A and Th17-rel...

Activation of macrophages in periapical granulomas occurs through the presence of cytokines, endotoxin and other genetic and epigenetic factors, allowing the initiation of inflammation and bone resorption. The present study aims to analyze the presence of CD133 protein (marker of stem cells) and the AR (androgen receptor) protein in biopsies of hum...

Activation of macrophages in periapical granulomas occurs through the presence of cytokines, endotoxin and other genetic and epigenetic factors, allowing the initiation of inflammation and bone resorption. The present study aims to analyze the presence of CD133 protein (marker of stem cells) and the AR (androgen receptor) protein in biopsies of hum...

High plasmatic levels of aldosterone cause hypertension and contribute to progressive organ damage to the heart, vasculature, and kidneys. Recent studies have demonstrated a role for the immune system in these pathological processes. Aldosterone promotes an inflammatory state characterized by vascular infiltration of immune cells, reactive oxidativ...

J. Neurochem. (2011) 118, 760–772. Nitric oxide (NO) has been proposed to down-regulate NMDA receptors (NMDA-Rs) in a homeostatic manner. However, NMDA-R-dependent NO synthesis also can cause excitotoxic cell death. Using bicuculline-stimulated hippocampal and cortical cell cultures, we have addressed the role of the brain-derived neurotrophic fact...

Hemodialysis patients (HD) display high rates of cardiac diseases and mortality. In chronic kidney disease, vascular injury leads to coronary artery disease, heart failure, and stroke. Carotid intima-media thickness (CIMT) measurements are currently widely used in randomized controlled trials (RCTs) to study the efficacy of interventions. An RCT wa...

Vascular calcification is caused by the deposition of basic calcium phosphate crystals in blood vessels, myocardium, and/or cardiac valves. Calcification decreases artery wall compliance, and arterial calcification is associated to mortality in hyperphosphatemic renal failure and diabetes mellitus. The calcification of the tunica media characterize...

To determine if maternal plasma ffDNA is increased early in pregnancies which subsequently develop preeclampsia (PE) and intrauterine growth restriction (IUGR). Blood was obtained at 11-14 weeks and plasma stored. Among those who delivered a male infant and had a birth weight under the tenth centile and/or PE, we divided them into those who deliver...

Excessive production of aldosterone leads to the development of hypertension and cardiovascular disease by generating an inflammatory state that can be promoted by T cell immunity. Because nature and intensity of T cell responses is controlled by dendritic cells (DCs), it is important to evaluate whether the function of these cells can be modulated...

E Prostanoid (EP) receptors play an important role in urinary Na(+) excretion. In the kidney, the epithelial sodium channel (ENaC) is the rate-limiting-step for Na(+) reabsorption. We hypothesized that activation of EP1/EP3 regulates the expression of ENaC in the face of renin-angiotensin-aldosterone-system (RAAS) activation. In primary cultures of...

Recent studies have shown that the epithelial sodium channel (ENaC) is expressed in vascular tissue. However, the role that ENaC may play in the responses to vasoconstrictors and NO production has yet to be addressed. In this study, the contractile responses of perfused pressurized small-diameter rat mesenteric arteries to phenylephrine and seroton...

Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known. To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. Patients and methods: Seventy fi...

Background: Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known. Aim: To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. Patients and me...

We thank Renke et al1 for their interest in our recent article.2 The clinical study by Renke et al1 indicates that spironolactone, combined with angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, may act as an antioxidant, as measured by the urinary excretion of 15-F2t-isoprostane, without producing changes in syste...

Chronic renal failure causes left ventricular hypertrophy, but the molecular mechanisms involved remain unknown. We, therefore, investigated whether the mineralocorticoid receptor is implicated in the cardiac hypertrophy observed in uremic rats and whether mineralocorticoid receptor blockade could be protective in chronic renal failure. Experimenta...

We set out to identify molecular mechanisms underlying the onset of necrotic Ca(2+) overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca(2+) chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca(2+) was...

Inhibition of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) with bumetanide reduced contractile responses to phenylephrine (PE) in male rat aortas (129+/-4% of 60 mM KCl-induced contraction control vs 108+/-7% bumetanide; PE 10(-5) M; P<0.01) but did not change equivalent responses in female rat aortas. Removal of the endothelium blunted the effect o...

The response of renal inner medullary (IM) collecting duct cells (mIMCD3) to high NaCl involves increased expression of Gadd45 and p53, both of which have important effects on growth and survival of the cells. However, mIMCD3 cells, being immortalized by SV40, proliferate rapidly, which is known to sensitize cells to high NaCl, whereas IM cells in...